CN107320726A - Applications of the LncRNA TUG1 in the dryness for preparing regulation and control periodontal ligament stem cell maintains the medicine of ability - Google Patents
Applications of the LncRNA TUG1 in the dryness for preparing regulation and control periodontal ligament stem cell maintains the medicine of ability Download PDFInfo
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Abstract
The invention discloses applications of the LncRNA TUG1 in the dryness for preparing regulation and control periodontal ligament stem cell maintains the medicine of ability.Present invention firstly discovers that LncRNA TUG1 have played important regulating and controlling effect in periodontal ligament stem cell dryness maintenance process, when LncRNA TUG1 are lowered, PDLSCs propagation, self-renewing, differentiation, transfer ability are suppressed, thereby confirm that the potential target spot that LncRNA TUG1 can be maintained as multipotential stem cell dryness, promotion is developed new on LncRNA TUG1 related drugs or the factor, and most it applies to regenerative medicine field at last, really precisely medical treatment is reached clinically.
Description
Technical field
The present invention relates to oral tissue regeneration art field, and in particular to LncRNA-TUG1 is preparing periodontal
The dryness of film stem cell maintains the application in the medicine of ability.
Background technology
Paradenlal tissue regeneration is one of emphasis of dentistry research, is Periodontics, maxillofacial surgery, correction, repaiies
The common objective of multidisciplinary area research such as go back to school.In recent years, the progress on tooth steam cell and tissue engineering technique
New research direction is brought to the regeneration of periodontium biology.Seo in 2004 etc. utilizes single cell clone technology, from human body
It is successfully separated in periodontal membrane tissue and identifies a kind of new adult stem cell, i.e. periodontal ligament stem cell, is that oral cavity carries out biology
New approaches have been opened up in function reparation.
Periodontal ligament stem cell (PDLSCs) is the adult that a class is easier to obtain, mesenchyma is originated in clinical oral work
Stem cell；The heterogeneous multipotential stem cell of to be also one group have multi-lineage potential, containing fibroblast, Gegenbaur's cell, into
The various kinds of cell composition such as cement cell and undifferentiated precursor stem cell, the potential with the newborn periodontium of synthesis, can divide a word with a hyphen at the end of a line
In diseased Root Surfaces and migrated, bred, a series of biological actions such as break up, formed newborn periodontium structure, set up new
Attachment relationship, plays extremely important leading role in periodontal regenerative.It can express stem cell labeling thing and possess stem cell
Sample characteristic (stem-cell-like ability), possesses self-renewing and Multidirectional Differentiation ability；Higher propagation can be shown
And clonality, the Regeneration and Repair of periodontium can be maintained.In vitro by appropriate induction can be formed bone, cartilage,
The Various Tissues such as nerve, fat, blood vessel；Possess the potential ability for being divided into Gegenbaur's cell or cementoblast, and can be in body
Cementum-parodontium-alveolar bone spline structure thing is formed after interior transplanting, provide can for tooth and the regeneration of periodontium biology
Energy；In bone tissue maintenance, osteanagenesis, periodontal remodeling, reparation and the orthodontic treatment of clinical oral, PDLSCs can play differentiation,
Propagation, self-renewing, migration etc. are acted on, to promote Periodontium remodeling, the formation of biological root of the tooth, bone tissue healing and osteanagenesis
Aspect provides important clinical value.The proposition that taken the lead in the world of present inventor seminar early stage utilizes tooth
Related stem cells carry out the new concept of biological dental root regeneration, and have carried out serial related In vitroandin vivotrial, such as in meiofauna
Successful regeneration goes out the biological root of the tooth that can normally function on model；The periodontal that autologous allosome periodontal ligament stem cell and Vc are induced
Film stem cell diaphragm is used for regeneration, and achieves good effect；Meanwhile, it is found that the expression for suppressing miRNA-21 can promote
Enter periodontal ligament stem cell Osteoblast Differentiation and regeneration.
In human genome research, scholars have found that a kind of length exceedes 200bp non-coding RNA (long non
Coding RNA, lncRNA), this kind of RNA not encoding proteins in itself, by eukaryotic gene group is transcribed, in the form of RNA
Exist in a variety of aspects, such as the expression of epigenetic regulation, transcriptional control and post-transcriptional control controlling gene.Research
It has been shown that, LncRNA participates in numerous life regulation activities：Epigenetics regulation can be carried out to protein coding gene；Directly adjust
Genetic transcription and protein degradation；Participate in some organelles generating process and intracellular molecules subcellular fraction transport, and often with
Gene imprinting phenomenon is relevant.
The expression product of taurine up-regulated gene 1 (Taurine upregulated gene 1, TUG1) is a kind of long-chain
Non-coding RNA.Most early in being found in mouse retinal cells, express, can draw after knocking out TUG1 in nucleus and cytoplasm
Retinal development deformity is played, causes cell growth to slow down or apoptosis.LncRNA-TUG1 is located at human chromosomal 22q12.2, length
About 7.1kb, with no more than 100 amino acid of several open reading frames but most long coding, it is taken as that it is non-volume
Code RNA.It can with polycomb repressive complex 2 (PRC2) protein binding for methylating, so as to regulate and control certain
The expression of a little growth control genes.Silence TUG1 can cause cell growth to slow down or apoptosis, several and apoptosis-related
Gene equal up-regulated expression after silence TUG1.Three days, several and cell after TUG1siRNA transfections are carried out for retinal progenitor cells
The related gene expression up-regulation of apoptosis pathway, cell death increase, TUG1 normal expression may wither for suppressing some cells
Related gene is died to play an important role.TUG1 has adjustment effect to SM22 α in vascular smooth muscle cells.Strike after low TUG1, carefully
Intracellular growth slows down or apoptosis, SM22 α mRNA up-regulated expressions；It can suppress (the Polycomb of complex 2 with many comb albumen
Repressive complex 2, PRC2) in EZH2 protein bindings so that regulate and control it is some growth control genes expression；Endochylema
In EZH2 have methyl transferase activity and PDGF induce cell pseudopodium forming process in play a crucial role, draw
Interaction mechanism between TUG1 and EZH2, F-actin and its adjustment effect to vascular smooth muscle cells skeleton.Study people
Member is it has also been found that include some highly conserved P53 bindings sites, the DNA damage that can be mediated by P53 should near TUG1 promoters
Answering stimulates and up-regulated expression.
The dryness of stem cell maintains ability, be mainly reflected in high proliferation, low differentiation, self-renewing, possess transfer ability and
The expression (stemness associated genes) of dryness related gene (such as Sox2, KLF4, Nanog, c-myc and oct4),
It is typically considered to that the dryness of stem cell can be maintained.Recent research have also shown that, these main bodies of stem cell related gene expression
In some present tumours, and modulate tumor into knurl and transfer, dryness related gene and its signal path are probably tumour extremely
The mechanism for occurring and shifting.The promoter of silence miR-302-367 clusters can make embryonic stem cell lack stem cell phenotype and
Characteristic, and cell after miR-302-367 clusters is overexpressed in application on human skin cancer cell has Pluripotent embryonic stem cells characteristic, shows
For stem cell labeling Oct3/4, SSEA-3, SSEA-4, Sox2 and Nanog expression.
However, the dryness for not being related to LncRNA regulation and control Periodontal ligament stem cells also at present maintains the report of ability.
The content of the invention
For above-mentioned prior art, preparing periodontal ligament stem cell it is an object of the invention to provide LncRNA-TUG1
Dryness maintain ability medicine in application.
To achieve the above object, the present invention is adopted the following technical scheme that：
The first aspect of the present invention is preparing periodontal ligament stem cell there is provided LncRNA-TUG1 as biomarker
Dryness maintain ability medicine in application.
The second aspect of the present invention is preparing the dry of positivity regulation and control periodontal ligament stem cell there is provided LncRNA-TUG1 accelerator
Property maintain ability medicine in application.
In above-mentioned application, the LncRNA-TUG1 accelerator refers to any activity that can improve LncRNA-TUG1, increasing
Plus the material of LncRNA-TUG1 expression quantity, for example increase the LncRNA-TUG1 of LncRNA-TUG1 expression quantity over-express vector.
In above-mentioned application, the dryness of the positivity regulation and control periodontal ligament stem cell maintains ability to include：Promote parodontium dry thin
The multiplication capacity of born of the same parents, the Multidirectional Differentiation ability for promoting periodontal ligament stem cell, the transfer ability for promoting periodontal ligament stem cell and promotion
The ability of cell dryness correlation factor expression.
The third aspect of the present invention is preparing the dry of negativity regulation and control periodontal ligament stem cell there is provided LncRNA-TUG1 inhibitor
Property maintain ability medicine in application.
In above-mentioned application, the LncRNA-TUG1 inhibitor includes antagonist, lower adjustment, retarding agent, blocking agent etc..
Any activity that can reduce LncRNA-TUG1, the material of reduction LncRNA-TUG1 expression quantity are used equally for the present invention.
It is used as preferred, the slow virus carrier that the LncRNA-TUG1 inhibitor is expressed for suppression LncRNA-TUG1.
In above-mentioned application, the dryness of the negativity regulation and control periodontal ligament stem cell maintains ability to include：Suppress parodontium dry thin
The multiplication capacity of born of the same parents, the Multidirectional Differentiation ability for suppressing periodontal ligament stem cell, the transfer ability for suppressing periodontal ligament stem cell and suppression
The ability of cell dryness correlation factor expression.
The fourth aspect of the present invention there is provided it is a kind of regulate and control periodontal ligament stem cell dryness maintain ability pharmaceutical composition,
Described pharmaceutical composition contains above-mentioned LncRNA-TUG1 accelerator or the LncRNA-TUG1 inhibitor of effective dose.
Further, also included in described pharmaceutical composition：Pharmaceutically acceptable carrier.
" pharmaceutically acceptable carrier " is conventional drug administration carrier, including various excipient or diluent etc..
Above-mentioned technical proposal has the advantages that：
Make present invention firstly discovers that LncRNA-TUG1 has played important regulation and control in periodontal ligament stem cell dryness maintenance process
With when LncRNA-TUG1 is lowered, PDLSCs propagation, self-renewing, differentiation, transfer ability are suppressed, thereby confirmed that
The potential target spot that LncRNA-TUG1 can be maintained as multipotential stem cell dryness, promotion is developed new on LncRNA-TUG1 phases
Medicine or the factor are closed, and most it applies to regenerative medicine field at last, reaches clinically really precisely medical treatment.
Brief description of the drawings
The Figure of description for constituting the part of the application is used for providing further understanding of the present application, and the application's shows
Meaning property embodiment and its illustrate be used for explain the application, do not constitute the improper restriction to the application.
Fig. 1：The biological characteristic research result of periodontal ligament stem cell；A is the PDLSCs (P0) of original cuiture；B is the 3rd
The PDLSCs (P3) for being commissioned to train foster；C is the qualification result of stem cell surface marker；D and E are respectively PDLSCs skeletonization to, fat
To the ability of induction differentiation.Scale bar in A, B, D, E：200μm.
Fig. 2：Slow virus carrier transfects PDLSCs to reduce TUG1 expression .A. immunofluorescence dyeings (scale bar：
200um)；B.qRT-PCR.
Fig. 3：TUG1 is to periodontal ligament stem cell multiplication capacity, the influence of Cellular cycle and apoptosis ability；In figure, A.EdU shows
Show the multiplication capacity of sh-NC and sh-TUG1-2# groups；B.CCK-8 Faxians show the multiplication capacity of sh-NC and sh-TUG1-2# groups；
C.MTT Faxians show the multiplication capacity of sh-NC and sh-TUG1-2# groups；D. colony formation shows sh-NC and sh-TUG1-2#
The cell propagation and self-renewal capacity of group；The influence of E, F.TUG1 to periodontal ligament stem cell Cellular cycle and apoptosis ability.(with
p<0.05 is statistically significant；*p<0.05、**p<0.01), Scale bar in A, D：200μm.
Fig. 4：Influences of the TUG1 to Periodontal ligament stem cell Multidirectional Differentiation ability；In figure, A, B.ALP dyeing (7d) and ALP
Activity；C, D. Alizarin red staining (21d) and calcium ion concentration；E. expression feelings from skeletonization to correlation factor (ALP, Runx2, OCN)
Condition；F, G, H. oil red O stain and the expression of into fatty correlation factor.Scale bar in A, C, F：200μm.
As a result show that sh-TUG1-2# groups are on a declining curve compared with empty carrier group.(with * p<0.05 is statistically significant).
Fig. 5：Influences of the TUG1 to Periodontal ligament stem cell transfer ability；In figure, A tests for Transwell；B is cut
Experiment；As a result it is in reducing tendency, Scale bar compared with the transfer ability of empty carrier group (sh-NC) to show sh-TUG1-2# groups：200μ
m.(with * p<0.05 is statistically significant).
Fig. 6：Influences of the TUG1 to Periodontal ligament stem cell dryness correlation factor；In figure, A. dryness correlation factor mRNA water
Flat change；B. the change of dryness correlation factor protein level.
Embodiment
It is noted that described further below is all exemplary, it is intended to provide further instruction to the present invention.Unless another
Indicate, all technologies used herein and scientific terminology are with usual with general technical staff of the technical field of the invention
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe embodiment, and be not intended to restricted root
According to the illustrative embodiments of the present invention.As used herein, unless the context clearly indicates otherwise, otherwise singulative
It is also intended to include plural form, additionally, it should be understood that, when in this manual using term "comprising" and/or " bag
Include " when, it indicates existing characteristics, step, operation and/or combinations thereof.
As background technology is introduced, the dryness maintenance of LncRNA regulation and control Periodontal ligament stem cells is not related to also at present
The report of ability.Based on this, the present invention regulates and controls the experiment in vitro that PDLSCs dryness maintains ability by LncRNA-TUG1, and right
Its related mechanism carries out Molecular level study, it is proposed that LncRNA-TUG1 is maintained in the dryness for preparing regulation and control periodontal ligament stem cell
New application in the medicine of ability.
In order that technical scheme can clearly be understood by obtaining those skilled in the art, below with reference to tool
The embodiment of body describes technical scheme in detail.
Embodiment 1：The biological characteristic research of periodontal ligament stem cell
1. the separation and culture of Periodontal ligament stem cell
The sterile periodontium pulled out people's impacted third molar, gently peel off around it, takes the periodontal group in stage casing under anesthesia
Knit, cleaned, shredded repeatedly with PBS, be placed at the digestive juice of enzyme containing NTx (3g/L) and the enzymes of Dispase II (4g/L), 37 DEG C
Digestion 40 minutes, crosses 70um cell sieves and collects cell, 1000 revs/min, centrifuge 5 minutes, remove the liquid on upper strata, with fresh
Nutrient solution suspends into single cell suspension again.Cell is inoculated in 25cm2In Tissue Culture Flask, (contain 15% in α-MEM culture mediums
Hyclone, 2mmol/L glutamine, 100U/ml penicillin and 100 μ g/ml streptomysins) in 37 DEG C, 5%CO2Culture, every
Change within 2-3 days liquid 1 time, cell growth condition is observed under inverted phase contrast microscope.When cell growth to 80% converging state, use
0.25% trypsase presses 1：2 or 1：3 had digestive transfer cultures.
As a result Figure 1A and Figure 1B are seen.
2. self-renewal capacity detects the expression with periodontal ligament stem cell mark
Using flow cytometry, the mescenchymal stem cell mark such as observation periodontal ligament stem cell STRO-1, CD146, CD45, CD31
The expression of will thing.
As a result Fig. 1 C are seen.
3. Multidirectional Differentiation ability is detected
By periodontal ligament stem cell respectively skeletonization to inducing culture and fat into inducing culture cultivate 3 weeks, then
Its multi-lineage potential is detected by Alizarin red staining, oil red O stain and RT-PCR technology respectively.
As a result Fig. 1 D and Fig. 1 E are seen.
The PDLSCs being separately cultured it can be seen from the above results can be divided into Gegenbaur's cell, fat by identifying and inducing
Fat cell etc., the multi-lineage potential for possessing stem cell.
Embodiment 2：LncRNA-TUG1 maintains the regulation and control of ability to influence on periodontal ligament stem cell dryness
1. the structure of slow virus carrier：
According to people's LncRNA-TUG1 sequences (ID:55000) primer is designed, primer is by the limited public affairs of Shanghai neck section biotechnology
Department synthesizes and purified.The pGenesil-1 plasmids of linearisation are connected to after annealing, the expression for building LncRNA-TUG1 (silence) is carried
Body slow virus, suppresses LncRNA-TUG1 expression.
It is specific as follows：
Vector：pLenO-GFP
Lenti-human-NC sequences：TTCTCCGAACGTGTCACGT(SEQ ID NO:1)；(Negative
Control)。
Lenti-human-sh1 TUG1
GPH-hTUG1-SH1 Forward Sequence
5’-GATCCCTGTTGACCTTGCTGTGAGAACTTCCTGTCAGATTCTCACAGCAAGGTCAACAGTTTTTG-
3’(SEQ ID NO:2)；
GPH-hTUG1-SH1 Reverse Sequence
5’-AATTCAAAAACTGTTGACCTTGCTGTGAGAATCTGACAGGAAGTTCTCACAGCAAGGTCAACAGG-
3’(SEQ ID NO:3)。
Lenti-human-sh2 TUG1
GPH-hTUG1-SH2 Forward Sequence
5’GATCCGCTTGGCTTCTATTCTGAATCCTTTCTTCCTGTCAGAAAAGGATTCAGAATAGAAGCCAAGC
TTTTTG3’(SEQ ID NO:4)；
GPH-hTUG1-SH2 Reverse Sequence
5’-AATTCAAAAAGCTTGGCTTCTATTCTGAATCCTTTTCTGACAGGAAGAAAGGATTCAGAATAGAAG
CCAAGCG-3’(SEQ ID NO:5)。
Lenti-human-sh3 TUG1
GPH-hTUG1-SH3 Forward Sequence
5’-GATCCGCTACAACTATCTTCCTTTACCTTCCTGTCAGAGTAAAGGAAGATAGTTGTAGCTTTTTG-
3’(SEQ ID NO:6)；
GPH-hTUG1-SH3 Reverse Sequence
5’-AATTCAAAAAGCTACAACTATCTTCCTTTACTCTGACAGGAAGGTAAAGGAAGATAGTTGTAGCG-
3’(SEQ ID NO:7)。
Lenti-human-sh4 TUG1
GPH-hTUG1-SH4 Forward Sequence
5’-GATCCGCAAGAGATAACTATGAAAGCCTTCCTGTCAGAGCTTTCATAGTTATCTCTTGCTTTTTG-
3’(SEQ ID NO:8)；
GPH-hTUG1-SH4 Reverse Sequence
5’-AATTCAAAAAGCAAGAGATAACTATGAAAGCTCTGACAGGAAGGCTTTCATAGTTATCTCTTGCG-
3’(SEQ ID NO:9)。
The different slow virus carriers built are investigated to LncRNA-TUG1 silencing efficiency, Fig. 2 is as a result seen.It can be seen by Fig. 2
Go out, sh-TUG1-2# silencing efficiency is most obvious.Therefore, follow-up experimental study is used for sh-TUG1-2#.
2. experiment packet：
Experiment is divided into three groups, is respectively：Control groups, sh-NC groups, sh-TUG1-2# groups.
Cell is cleaned with serum free medium, sh-TUG1-2# and sh-NC empty carriers add according to transfection procedure specification
Enter into cell.Use normal culture medium after 8-10h instead, be incubated after 24h in fluorescence microscopy Microscopic observation, green fluorescence occur and say
It is bright to transfect successfully, complete the associated verification that follow-up dryness maintains ability.
3. cell proliferation experiment：
EdU, MTT, CCK-8 method and colony formation detection cell proliferation rate；Cell cycle and apoptosis experiment detect it
Influence to cell characteristics, is as a result shown in Fig. 3.
As seen from Figure 3, silence LncRNA-TUG1, the multiplication capacity of cell weakens, apoptosis capacity enhancing.
4. Multidirectional Differentiation ability is detected：
(1) skeletonization is determined to differentiation capability：
ALP is dyed and Alizarin red staining, and carries out ALP activity, calcium ion concentration measure, is detected by real-time quantitative PCR
The expression change of skeletonization key factor Runx2, ALP and OCN gene.
(2) determined into fat to differentiation capability：
Carry out the measure of oil red dyeing and PPAR γ and the LPL factors.
The result of Multidirectional Differentiation ability detection is as shown in Figure 4.As seen from Figure 4, silence LncRNA-TUG1, cell
Skeletonization into fat to reduced capability.
5. transfer ability is detected：
Transfer ability is detected using Transwell and scratch experiment, as a result as shown in Figure 5.There is Fig. 5 to see
Go out, silence LncRNA-TUG1, the transfer ability of cell weakens.
6. the measure of dryness correlation factor：
The mRNA and protein level of dryness correlation factor are measured, as a result as shown in Figure 6.As seen from Figure 6, sink
Silent LncRNA-TUG1, cell dryness correlation factor expression weakens.
Above-described embodiment is preferably embodiment, but embodiments of the present invention are not by above-described embodiment of the invention
Limitation, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
SEQUENCE LISTING
<110>Shandong University
<120>Applications of the LncRNA-TUG1 in the dryness for preparing regulation and control periodontal ligament stem cell maintains the medicine of ability
<130>
<160> 9
<170> PatentIn version 3.5
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Claims (10)
1.LncRNA-TUG1 is as biomarker in the dryness for preparing periodontal ligament stem cell maintains the medicine of ability
Using.
2.LncRNA-TUG1 accelerator answering in the dryness for preparing positivity regulation and control periodontal ligament stem cell maintains the medicine of ability
With.
3. application as claimed in claim 2, it is characterised in that the LncRNA-TUG1 accelerator is increase LncRNA-TUG1
The LncRNA-TUG1 of expression quantity over-express vector.
4. application as claimed in claim 2, it is characterised in that the dryness of the positivity regulation and control periodontal ligament stem cell maintains ability
Including：Multiplication capacity, the Multidirectional Differentiation ability for promoting periodontal ligament stem cell, the promotion parodontium for promoting periodontal ligament stem cell are dry thin
The transfer ability of born of the same parents and the ability for promoting the expression of cell dryness correlation factor.
5.LncRNA-TUG1 inhibitor answering in the dryness for preparing negativity regulation and control periodontal ligament stem cell maintains the medicine of ability
With.
6. application as claimed in claim 5, it is characterised in that the LncRNA-TUG1 inhibitor includes：LncRNA-TUG1
Antagonist, lower adjustment, retarding agent or blocking agent.
7. the application as described in claim 5 or 6, it is characterised in that the LncRNA-TUG1 inhibitor is suppression LncRNA-
The slow virus carrier of TUG1 expression.
8. application as claimed in claim 5, it is characterised in that the dryness of the negativity regulation and control periodontal ligament stem cell maintains ability
Including：Multiplication capacity, the Multidirectional Differentiation ability for suppressing periodontal ligament stem cell, the suppression parodontium for suppressing periodontal ligament stem cell are dry thin
The transfer ability of born of the same parents and the ability for suppressing the expression of cell dryness correlation factor.
9. a kind of dryness of regulation and control periodontal ligament stem cell maintains the pharmaceutical composition of ability, it is characterised in that the drug regimen
Thing contains the LncRNA-TUG1 suppressions described in LncRNA-TUG1 accelerator or claim 5 described in the claim 2 of effective dose
Preparation.
10. pharmaceutical composition as claimed in claim 9, it is characterised in that also included in described pharmaceutical composition：Pharmaceutically may be used
The carrier of receiving.
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| CN116082450A (en) * | 2022-06-16 | 2023-05-09 | 山东大学 | Near-infrared ratio type pH fluorescent probe, preparation method thereof and application thereof in bone fracture resorption imaging |
| CN116622848A (en) * | 2023-05-24 | 2023-08-22 | 广东药科大学 | Application and product of long-chain non-coding RNATUG1 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110305867A (en) * | 2019-07-10 | 2019-10-08 | 山东如戴生物科技有限公司 | Regulate and control method and its reagent that fat stem cell stemness maintains ability |
| CN111808861A (en) * | 2020-07-22 | 2020-10-23 | 青岛思拓新源细胞医学有限公司 | Application of lncRNA in umbilical blood mesenchymal stem cell apoptosis caused by oxidative stress |
| CN111808861B (en) * | 2020-07-22 | 2021-04-13 | 青岛思拓新源细胞医学有限公司 | Application of lncRNA in umbilical blood mesenchymal stem cell apoptosis caused by oxidative stress |
| CN116082450A (en) * | 2022-06-16 | 2023-05-09 | 山东大学 | Near-infrared ratio type pH fluorescent probe, preparation method thereof and application thereof in bone fracture resorption imaging |
| CN116082450B (en) * | 2022-06-16 | 2024-06-04 | 山东大学 | Near-infrared ratio type pH fluorescent probe, preparation method thereof and application thereof in bone fracture resorption imaging |
| CN116622848A (en) * | 2023-05-24 | 2023-08-22 | 广东药科大学 | Application and product of long-chain non-coding RNATUG1 |
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