"Have you ever done anything to understand the specific mechanism of action of brain-derived neurofactors? It is not as popular as several other pathways?" Zhou Cheng asked more accurately and in-depth, from a purely academic perspective.
Modern academics can be divided into pure academics and catered academics. If real academic issues are to be very in-depth, the depth will reach a very precise angle, and there are too many complicated possibilities at every step.
Basically, it is difficult to exhaust them in the short term. This is actually why PhDs or scientific research teams who really know how to do academic work will not be afraid of not being able to publish articles, but just look at the significance of the published articles.
But in fact, many articles are only to promote the development of the subject, and will not directly touch the threshold of the subject's development to the next stage. From an overall perspective, it requires a process of accumulation and accumulation to overcome the barrier in one fell swoop!
Yang Yifeng looked at Zhou Cheng and knew that Zhou Cheng would not make a mistake.
But he couldn't answer Zhou Cheng's question at the moment, so he said, "Just wait for me."
After saying that, Yang Yifeng closed his eyes slightly and began to meditate, as if he was extracting something.
In reality, Yang Yifeng has never really shown his true strength and original complete talent.
But in the simulated world, Zhou Cheng knew that Yang Yifeng seemed unreliable, but in fact he had a strong knowledge reserve and knowledge system. Moreover, Yang Yifeng's reserve and system were different from others. He just
Storage requires temporary sorting and extraction of the corresponding key ingredients——
Yang Yifeng will often browse articles and then memorize them, but he will not analyze them in depth. Being able to remember them does not mean that he will refine what he remembers into his own master. He is a knowledgeable and knowledgeable person.
Zhou Cheng didn’t bother Yang Yifeng either!
Ding Changle and others were even more afraid to speak, because the background just listed by Yang Yifeng was already beyond the in-depth research content of most general fund projects.
The current general research projects in China basically involve simple pathways, which is considered very in-depth!
Each disease has many pathways, including popular and non-popular pathways. Then we start to play marginal cards and use effective drugs to act on the cells to see if the drugs can increase the level of expression of the corresponding pathways to verify
Whether the drug has a promoting or negative effect on a certain disease.
This is very in-depth and can be considered a very top-notch research project.
However, the rebound that Yang Yifeng touched this time was obviously not such a simple matter.
However, Yang Yifeng did not keep everyone waiting for a long time, and said: "When BDNF repairs nerves, or promotes neuronal connections, its main mechanisms of action are as follows."
"Promote neuronal growth and connections
"BDNF can stimulate the growth cones of neurons and promote the growth and connection of neurons. After BDNF binds to its high-affinity receptor TrkB, it can activate a variety of signaling pathways, such as Akt, ERK, CREB and other pathways, thereby promoting the growth of neurons.
Growth and synapse formation. In addition, another mechanism of action of BDNF is to promote neuronal connections by regulating synaptic plasticity. BDNF can strengthen synaptic connections, thereby promoting the maturation and survival of neurons.
"Promote neuronal metabolism
"BDNF can promote the metabolism of neurons, increase the level of energy metabolism, enhance the stability of cell membranes and prevent oxidative stress. BDNF can promote the energy metabolism of neurons and improve the metabolic level of cells by activating the AMPK signaling pathway. In addition, BDNF also
It can enhance the stability of neuronal cell membranes and prevent the occurrence of oxidative stress by activating the NF-κB signaling pathway.
"Reduce apoptosis
"BDNF can reduce neuronal apoptosis and enhance the anti-apoptotic ability of cells by activating signaling pathways such as Akt. BDNF can regulate cell apoptosis through two receptors, TrkB and p75NTR. TrkB receptor activation can activate Akt through
signaling pathway to inhibit cell apoptosis, and p75NTR receptor activation can promote cell apoptosis.
"The regulatory pathways mainly include TrkB receptor, p75NTR receptor, CREB signaling pathway, ERK signaling pathway, and Akt signaling pathway. The current depth of research at the cell experimental level is roughly the same."
"What you mean is that I need to explore the role of BDNF in these pathways and then find a suitable point?"
Hearing this, Zhou Cheng nodded and then shook his head, ignoring what others added: "TrkB is a receptor, a high-affinity receptor for BDNF. Activating TrkB will promote the growth and connection of neurons, promote cell metabolism and reduce apoptosis."
Death."
"To summarize, it promotes metabolism and reduces cell apoptosis."
"p75NTR is a low-affinity receptor for BDNF. It enhances TrkB signal transmission and enhances the growth and connection of neurons by binding to TrkB. However, the activation of p75NTR can also promote cell apoptosis, so its regulation is very important.
.”
"To summarize, control."
"CREB is a transcription factor that can promote the expression and release of BDNF by activating the CREB signaling pathway. BDNF can activate the CREB signaling pathway by activating the TrkB receptor, forming a positive feedback regulatory loop."
"This is positive feedback."
"The ERK signaling pathway is an important signaling pathway for BDNF to promote the growth and connection of neurons. Activation of ERK can promote the growth and connection of neurons, and also plays an important role in synaptic plasticity and learning and memory. BDNF can be stimulated by activating TrkB.
body to activate the ERK signaling pathway."
"This is equivalent to a bypass."
"The Akt signaling pathway is an important signaling pathway for BDNF to regulate cell apoptosis. The activation of Akt can inhibit cell apoptosis and enhance the cell's anti-apoptotic ability. BDNF can activate the Akt signaling pathway by activating the TrkB receptor." Zhou Chengkan
And talking.
However, after Zhou Cheng almost repeated the main mechanisms of the several pathways mentioned by Yang Yifeng, Yang Yifeng said in shock: "How many articles have you memorized? How many years have you memorized it?"
Yang Yifeng's words caused Ding Changle to cough, which seemed to be a signal to Yang Yifeng not to say something too straightforward, lest he would be too evil and the wind would destroy him.
After all, Jiang Hong is still in front of him now.
Jiang Hongze is a bit stupid.
If the things Yang Yifeng and Zhou Cheng said were found out, there would be no problem, but if they were said like this, it would be a bit too evil.
The other graduate students and Ph.D. students were all dumbfounded, because any point mentioned by Zhou Cheng and Yang Yifeng was probably enough to support their graduation. Today, the level of doctoral students in the world has not yet reached such incredible heights.
Just go down two levels and you can graduate easily.
Some of the more relaxed majors go deep into a molecular level, and it is not difficult to graduate.
Zhou Cheng ignored it and continued: "We can find that TrKB is a special bond and adjustment point."
"Then, we can focus on the more upstream regulatory nodes regulated by TrKB:
"Neuron surface molecules: Neuron surface molecules such as Integrin, NCAM, L1, N-cadherin, etc. can regulate the expression, distribution and signal transduction of TrkB receptors.
"Signal transduction regulatory enzymes: Signal transduction regulatory enzymes such as SH2, PTP, GSK3β, etc. can regulate the activity and stability of the TrkB signaling pathway.
"Extracellular matrix components: Extracellular matrix components such as Laminin, Fibronectin, Collagen, etc. can regulate the adhesion, growth and connection of neurons.
“There are further downstream regulatory nodes:
"MEF2: MEF2 is a transcription factor that participates in the development and maturation of neurons and can be regulated by the CREB and NF-κB signaling pathways.
"mTOR: mTOR is a cell metabolism regulatory protein that plays an important role in neuronal growth and synaptic plasticity and can be regulated by the Akt and PI3K signaling pathways.
"MAPKAPK2: MAPKAPK2 is a cytoskeletal regulatory protein that plays an important role in neuronal morphology and connection and can be regulated by the ERK signaling pathway.
"Bcl-2 family: The Bcl-2 family is a group of proteins that regulate apoptosis. It plays an important role in the survival and death of neurons and can be regulated by the Akt signaling pathway and the NF-κB signaling pathway."
At this moment, in the eyes and ears of others, what Zhou Cheng said has become, jilly guala, jiili guala, as if in a foreign language.
But Yang Yifeng listened very carefully.
Zhou Cheng continued: "So we can focus on more detailed areas, such as messenger mRNA that promotes BDNF regulation."
"The main ones are as follows -"
"BDNF mRNA: BDNF mRNA is the gene encoding BDNF, the ligand of the TrkB signaling pathway. It is widely expressed in neurons and can activate the signaling pathway after binding to the TrkB receptor.
Ntrk2 mRNA: Ntrk2 mRNA is the gene encoding the TrkB receptor. It is widely expressed in neurons and can activate signaling pathways after binding to BDNF.
RasGRP1 mRNA: RasGRP1 mRNA encodes Ras guanyl releasing protein 1, which is a protein involved in signal transduction and plays an important role in the TrkB signaling pathway.
Pten mRNA: Pten mRNA encodes protein tyrosine phosphatase, which can regulate the activity of the PI3K/Akt signaling pathway, thus affecting the growth and survival of neurons.
Gab1 mRNA: Gab1 mRNA encodes a cytokine receptor tyrosine kinase-binding protein 1 and can regulate the activity of the TrkB signaling pathway.
Shc mRNA: Shc mRNA encodes a SHC transcription factor and plays an important role in the TrkB signaling pathway."
When he arrived here, Zhou Cheng paused for a while. After Yang Yifeng calmed down for nearly a minute or two, he saw everyone put down their pens.
But only Zhou Cheng and Yang Yifeng knew that the depth of the current discussion was still not enough to support Yang Yifeng in solving the current problem. It had not yet reached the point where Yang Yifeng was awakened.
"The main influencing factors that affect the level of mRNA transcribing BDNF are as follows6"
"Nerve growth factor (NGF): NGF can activate signaling pathways such as PI3K/Akt and MAPK/ERK through the TrkA receptor, thereby affecting the activity of the TrkB signaling pathway and the expression level of related mRNA.
"Inflammatory factors: Inflammatory factors such as IL-6, TNF-α, etc. can affect the activity of the TrkB signaling pathway and the expression levels of related mRNA by activating JAK-STAT, NF-κB and other signaling pathways.
"Neuron activity: Neuron activity can affect the activity of the TrkB signaling pathway and the expression level of related mRNA through Ca2+, CREB and other signaling pathways.
"miRNA: miRNA is a type of non-coding RNA that can affect its translation and degradation by binding to the target of mRNA, thereby affecting the expression level of mRNA related to the TrkB signaling pathway.
"Transcription factors: Transcription factors such as CREB, NFKB, STAT3, etc. can regulate the expression levels of mRNA related to the TrkB signaling pathway."
"Yi Feng, have you noticed? These three layers are actually a spherical body, and the one in the center is actually not one of these popular targets, but rather a less popular target called BDNF. I think
You can work more on this..."
"Perhaps I can provide you with some ideas to solve your current problems."
After Zhou Cheng finished speaking, Yang Yifeng nodded, closed his eyes again and wondered what he was thinking about.
And just after Zhou Cheng babbled for a while, Jiang Hong slammed the table: "Professor Ding, who heard the rumor before that our Dr. Zhou Cheng is just a scalpel doctor?"
"If I find out this again, I will tear his mouth open."
"Whether he is a thesis doctor or a scalpel doctor, neither is enough to describe our Dr. Zhou. With this kind of scientific research ability, even if it is put into the field of internal medicine, Zhou Cheng said that he is fifth, and he dares to consider himself as the top four. It is very difficult for him in China."
Find it out?" Jiang Hong's emotions were extremely complicated when he said this.
There is admiration, reluctance, loneliness, happiness, and even an inexplicable sourness.
Why would such a talented person end up in the orthopedics department? Why did this genius, who was born for neurosurgery, end up in the carpentry department?
After Ding Changle sensed the different flavor in Jiang Hong's words, he immediately said: "Professor Jiang, what you are reminding me is that I feel that Dr. Zhou in our department is indeed a bit overqualified and overqualified for his current position.
the meaning of."
"But it would be better to have a more comprehensive resume."
"Professor Jiang, please don't forget that the lancet our Dr. Zhou holds in clinical practice is not an ordinary lancet. That's why I asked him to be in charge of the trauma center." Ding Changle said.
Not only did he explain it to Jiang Hongzai, he also explained it to Zhou Cheng.
In fact, when Zhou Cheng entered the field of rehabilitation and made such a big move, Ding Changle carefully considered Zhou Cheng's future development direction and the speed of his professional title promotion.
I thought I would give it another try after a while, but after all, Zhou Cheng's professional title promotion was a bit too fast.
But now it seems that if we really want to make the most of everything, we still need to promote Zhou Cheng to associate professor as soon as possible, so that he can fully unleash his abilities.
For a topic paper published in the journal Science, Zhou Cheng actually found a way to solve the problem and go a step further. This ability is simply incredible.
Zhou Cheng only smiled and said: "Professor Ding, Professor Jiang, I just discussed this direction with Yi Feng, but we didn't actually come up with anything."
Zhou Cheng could point it out, but in view of the 'damage' caused to Luo Yun before, Zhou Cheng held back a little more this time and let Yang Yifeng pierce the last layer of window paper by himself. He had already sent him away
Arrive at the window door.
Such a sense of breakthrough and support is the true position of being both a teacher and a friend, rather than holding Yang Yifeng and throwing him through the door.
Sure enough, Yang Yifeng did not disappoint Zhou Cheng!
After Zhou Cheng finished speaking, he pursed his lips and said, "I probably know what to do next. Thank you Zhou Cheng, thank you Master, thank you Professor Jiang, and thank you all fellow apprentices."
"Master, I have to do this project as soon as possible, so in the next period of time, I would like to ask some brothers to cooperate with me? Do you think it is suitable?"
"I will not touch some small articles that may be produced during this process, and will use them for the juniors' graduation." Yang Yifeng asked Ding Changle for help.
The main reason is that Yang Yifeng has graduated and is now taking care of students. Strictly speaking, he should no longer occupy the resources within the division, but there is no way, Yang Yifeng has too few available manpower.
Ding Changle nodded.
Jiang Hong said: "How about I send you a few people?"
Ding Changle nodded and then hurriedly shook his head: "Professor Jiang, there is no need for this. We still have people in the orthopedics department for the time being. Thank you for your kindness."
Now I am rejecting people thousands of miles away again.
Jiang Hong then said: "Xiao Zhou, it's really a pity that I missed the opportunity to collaborate with you on this project. I sincerely invite you to come to my laboratory and the research group, and just participate in the project meetings occasionally."
,do you think it's OK?"
"You can give me money or anything else!" Jiang Hong's eyes were sincere and his tone was serious.