CN108872404A - The application of overlength chain saturated fatty acid or its detection reagent in metabolic syndrome risk profile - Google Patents
The application of overlength chain saturated fatty acid or its detection reagent in metabolic syndrome risk profile Download PDFInfo
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Abstract
The present invention provides the application of overlength chain saturated fatty acid or its detection reagent in metabolic syndrome risk profile, specifically, present invention determine that overlength chain saturated fatty acid and metabolic syndrome have a significant negative customers, and overlength chain saturated fatty acid is reduced as metabolic syndrome scores and is reduced, and it can be according to the level of over-long chain fatty acid, on the one hand it can be used to predict the risk of metabolic syndrome, on the other hand, over-long chain fatty acid can be strengthened by diet or take over-long chain fatty acid replenishers, early prediction or Disease Intervention are carried out to metabolic syndrome.
Description
Technical field
The present invention relates to fields of biomedicine, and in particular, to overlength chain saturated fatty acid or its detection reagent are being metabolized
Application in the prediction of syndrome risk.
Background technique
With China's expanding economy, huge variation is had occurred in Dietary Pattern of Residents, disease trend.According to 2002 I
Animal food and grease over-consumption in state's resident's nutrition and health survey, city dweller and rich rural resident's diet
Increase, from 1992 to 2002 year, dietary fat energy supply ratio is by 22% sharp increase to 29.8%.The change of this diet structure
The balance and its internal metabolic process of body fat acid are very likely influenced, and then influences the occurrence and development of disease.It is same with this
When, fat prevalence has spread to Asia from western countries, becomes the chief threat of global public health.The fertilizer of China
Fat and overweight rate by 22.8% in 2002 and 7.1% be increased to 2010 30.6% and 12.0%.And obesity can pass through
The secretion for influencing insulin, sex hormone and Adipocyte Factor etc., causes a series of metabolic disorder, including hyperglycemia, hyperlipidemia and
Hypertension.Excessive palmitinic acid (C16:0) it takes in, insulin sensitivity can be reduced, increase blood lipid and blood pressure.
There is an urgent need in the art to study the relationship of overlength chain saturated fatty acid and metabolic syndrome, thus set up it is simple,
Reliable metabolic syndrome risk forecast model.
Summary of the invention
The object of the present invention is to provide overlength chain saturated fatty acids or its detection reagent in metabolic syndrome wind
Application in the prediction of danger.
First aspect present invention provides a kind of overlength chain saturated fatty acid or the purposes of its detection reagent, is used to prepare one
Kit, the kit is for detecting metabolic syndrome neurological susceptibility or its risk;
Wherein, the overlength chain saturated fatty acid is the overlength chain saturated fatty acid of carbon atom number >=20.
In another preferred example, the carbon atom number of the overlength chain saturated fatty acid is 20-24, preferably 20-23.
In another preferred example, the overlength chain saturated fatty acid is selected from the group:C20:0,C22:0,C23:0,C24:
0, or combinations thereof.
In another preferred example, the overlength chain saturated fatty acid is selected from the group:C20:0,0.18 (0.13,0.25),
C22:0,0.26 (0.18,0.35), C24:0,0.19 (0.13,0.26), or combinations thereof.
In another preferred example, the overlength chain saturated fatty acid is to be present in surpassing in mammal (such as people) blood
Chain saturated fatty acids or in the detectable overlength chain saturated fatty acid of mammal (such as people) blood.
In another preferred example, the metabolic syndrome includes metabolic disorder related disease.
In another preferred example, the metabolic disorder related disease is selected from the group:Obesity, hypertension, hyperlipidemia, high blood
Sugar, coronary heart disease, myocardial infarction, Ischemic Stroke, diabetes, or combinations thereof.
In another preferred example, the detection includes auxiliary detection and/or early detection.
In another preferred example, be detected as blood testing, blood plasma detection or the serum detect.
In another preferred example, the test sample that the detection is directed to includes blood sample, plasma sample or serum sample
Product.
In another preferred example, the detection is a certain overlength chain saturated fatty acid of the sample of self-test in future object
Compared with content A1 overlength chain saturated fatty acid content A0 corresponding with normal population, if A1 is significantly higher than A0, prompt to test
The neurological susceptibility (or risk) of the metabolic syndrome of object is lower.
In another preferred example, described " being significantly higher than " refers to A1/A0 >=2, preferably A1/A0 >=3, more preferably A1/A0 >=
4。
In another preferred example, if A1 is substantially less than A0, prompt the metabolic syndrome of test object neurological susceptibility (or suffer from
Sick risk) it is higher.
In another preferred example, described " substantially less than " to refer to A1/A0≤1/2, preferably, A1/A0≤1/3, more preferably,
A1/A0≤1/4。
In another preferred example, the quantity of the normal population is at least 100 people;Preferably at least 300 people;More preferably
At least 500 people, most preferably at least 1000 people.
In another preferred example, the detection reagent includes Mass Spectrometer Method reagent.
In another preferred example, the Mass Spectrometer Method reagent is selected from the group:Fatty acid standards (C20:0,C22:0,C23:
0,C24:0, or combinations thereof), bis- peanut docosahexaenoyl-sn-glycero -3- phosphocholine (1,2-dihenarachidoyl-sn- of 1,2-
Glycero-3-phosphocholine), methanol, methylene chloride, isooctane, n-hexane, the concentrated sulfuric acid, or combinations thereof.
In another preferred example, the detection reagent includes chain saturated fatty acids specific antibody.
In another preferred example, chain saturated fatty acids specific antibody coupling has or with detectable label.
In another preferred example, the detectable label is selected from the group:Chromophore, chemiluminescent groups, fluorogen, same to position
Element or enzyme.
In another preferred example, the chain saturated fatty acids specific antibody is monoclonal antibody or polyclonal antibody.
In another preferred example, the kit further includes point sample in the detection reagent and use on test board
Specification.
In another preferred example, the kit further includes detecting matched sample pre-treatments reagent and operation instruction
Book.
In another preferred example, the specification describes detection method and according to A1Value prediction metabolic syndrome danger
Method.
In another preferred example, the specification indicates the following contents:
(i) with total restatement of Fatty Acids in Plasma, when blood plasma overlength chain saturated fatty acid level is 0.1-1%, preferably,
0.15-0.9%, more preferably, when 0.17-0.6%, metabolic syndrome risk score≤2 (preferably, 1-2) shows Metabolic syndrome
It is lower to levy neurological susceptibility (or risk);
(ii) with total restatement of Fatty Acids in Plasma, when blood plasma overlength chain saturated fatty acid level is 0.1-1%, preferably
Ground, 0.13-0.9%, more preferably, when 0.15-0.7%, metabolic syndrome risk score≤3 (preferably, 2-3) shows to be metabolized
Syndrome neurological susceptibility (or risk) is lower;
(iii) with total restatement of Fatty Acids in Plasma, when blood plasma overlength chain saturated fatty acid level is 0.1-1%, preferably
Ground, 0.14-0.9%, more preferably, when 0.15-0.8%, metabolic syndrome risk score≤4 (preferably, 3-4) shows to be metabolized
Syndrome neurological susceptibility (or risk) is higher;
(iv) with total restatement of Fatty Acids in Plasma, when blood plasma overlength chain saturated fatty acid level is 0.1-1%, preferably
Ground, 0.13-0.9%, more preferably, when 0.15-0.8%, metabolic syndrome risk score≤5 (preferably, 4-5) shows to be metabolized
Syndrome neurological susceptibility (or risk) is higher.
In another preferred example, the kit further includes the standard items of over-long chain fatty acid.
In another preferred example, the standard items are selected from the group:C20:0,C22:0,C23:0,C24:0, or combinations thereof.
In another preferred example, the detection includes that the cationic flame method (GC-FID) of gas-chromatography (GC)-is detected.
Second aspect of the present invention provide it is a kind of for detecting the kit of metabolic syndrome risk, including:
(a) reagent for overlength chain saturated fatty acid content in test sample, wherein the sample include blood sample,
Plasma sample or blood serum sample, the overlength chain saturated fatty acid include the overlength chain saturated fatty acid of carbon atom number >=20;
(b) overlength chain saturated fatty acid standard items;
(c) operation instructions.
In another preferred example, method described in third aspect present invention has been indicated in the specification.
In another preferred example, the standard items are selected from the group:C20:0,C22:0,C23:0,C24:0, or combinations thereof.
Third aspect present invention provides a kind of method for detecting metabolic syndrome risk, including step:
(a) test sample of subject is provided;
(b) content for measuring overlength chain saturated fatty acid in the sample is A1;
(c) step (b) is compared with the overlength chain saturated fatty acid content A0 of normal population sample, if A1 is significantly higher than
A0 then illustrates that the risk of test group metabolic syndrome is lower;
Wherein, the overlength chain saturated fatty acid is the overlength chain saturated fatty acid of carbon atom number >=20.
In another preferred example, the detection method is detected by method selected from the group below:Gas-chromatography sun from
Sub- flame method (GC-FID).
In another preferred example, the sample of the detection includes blood sample, plasma sample, blood serum sample.
In another preferred example, the method is non-therapeutic and nondiagnostic.
Fourth aspect present invention provides a kind of method for producing ready-mixed oil, including step:
(i) substrate oil is provided;
(ii) content of overlength chain saturated fatty acid in the substrate oil is detected, wherein the overlength chain saturated fat
Carbon atom number >=20 of fat acid;With
(ii i) is based on the content of overlength chain saturated fatty acid described in step (iii), and into the substrate oil, addition is pre-
The overlength chain saturated fatty acid of content is determined, to obtain the ready-mixed oil.
In another preferred example, total restatement that the predetermined content refers to the ready-mixed oil, the overlength chain saturated fat
The additive amount of fat acid is 0.5-20%, preferably, 1-15%, more preferably, 2-10%.
In another preferred example, the substrate oil is selected from the group:Peanut oil, canola oil, lotus seeds oil, or combinations thereof.
In another preferred example, the overlength chain saturated fatty acid of carbon atom number >=20 is selected from the group:C20:0,C22:
0,C23:0,C24:0, or combinations thereof.
It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention
It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, exist
This no longer tires out one by one states.
Detailed description of the invention
Fig. 1 shows blood plasma overlength chain saturated fatty acid and metabolic syndrome prevalence risk, wherein using
Restricted cubic spline is analyzed, and gender, age and dry farm work situation are adjusted in model.
Fig. 2 shows the relationship of blood plasma overlength chain saturated fatty acid and Metabolic syndrome scoring, is made using box-plot method
Figure.
Fig. 3 shows the reciprocation of blood plasma overlength chain saturated fatty acid and other factors.Wherein, OR value indicates fatty acid
One standard deviation of every increase, the increased size of metabolic syndrome risk.Gender, age and dry farm work situation are had adjusted in model.
Specific embodiment
The present inventor has found, overlength chain saturated fatty acid can be used as effectively for the first time by depth studying extensively
Predict the marker of metabolic syndrome risk (such as diabetes, coronary heart disease and artery sclerosis).The present invention passes through to 2008
The follow for being up to 2 years of name resident, it is determined that overlength chain saturated fatty acid and metabolic syndrome have significant negative customers, and
Overlength chain saturated fatty acid is reduced as metabolic syndrome scores and is reduced, and can be according to the level of over-long chain fatty acid, a side
Face can be used to predict the risk of metabolic syndrome, on the other hand, can be strengthened by diet over-long chain fatty acid or
Over-long chain fatty acid replenishers are taken, early prediction or Disease Intervention are carried out to metabolic syndrome.On this basis, the present inventor
Complete the present invention.
Overlength chain saturated fatty acid
As used herein, term " overlength chain saturated fatty acid " refers to the linear saturated fatty acids of carbon atom number >=20, e.g.,
The detectable C20 of blood plasma:0,C22:0,C24:0 saturated fatty acid.
Metabolic syndrome
In the present invention, described " metabolic syndrome " refers to that generation occurs for the substances such as the protein, fat, carbohydrate of human body
The pathological state for thanking to disorder is a complex set of metabolic disorder disease group, be cause diabetes cardiovascular and cerebrovascular disease it is dangerous because
Element.
Specifically, according to National Education Program's Adult Treatment Panel III
(ATPIII), as follows for the metabolic syndrome standard of Asian American:
1. waistline >=90cm (male), >=80cm (women)
2. triglycerides >=1.7mmol/L
3. high-density lipoprotein<1.03mmol/L (male),<1.29mmol/L (women)
4. systolic pressure >=130or diastolic pressure >=85mm Hg takes depressor
5. fasting blood-glucose >=5.6mmol/L takes antidiabetic drug, insulin injection
Metabolic syndrome patient can be diagnosed as by having 3 in above 5 or 3 or more.
In a preferred embodiment, the metabolic syndrome includes metabolic disorder related disease.
In a preferred embodiment, the metabolic disorder related disease is selected from the group:Obesity, hypertension, hyperlipidemia, height
Blood glucose, coronary heart disease, myocardial infarction, Ischemic Stroke, diabetes, or combinations thereof.
Detection reagent and detection method
The present invention relates to the levels for qualitatively and quantitatively detecting overlength chain saturated fatty acid in human body.These tests are this fields
Known.In test in human body detected overlength chain saturated fatty acid level, can be used for the stream of pre- metabolic syndrome
Row risk.
In the present invention, a variety of methods can be used qualitatively or quantitatively to detect the reaction between detection reagent-sample,
Preferred method such as gas-chromatography (GC)-flame ionization ditector.In the present invention, the overlength chain saturated fatty acid
Detection agent includes Mass Spectrometer Method reagent (such as bis- peanut docosahexaenoyl-sn-glycero -3- phosphocholine (1,2- of 1,2-
Dihenarachidoyl-sn-glycero-3-phosphocholine), methylene chloride, methanol, the concentrated sulfuric acid, isooctane).
The method of overlength chain saturated fatty acid content is to utilize chromatogram analysis method mentioned above in a kind of test sample
Carry out the qualitative and quantitative analysis of overlength chain saturated fatty acid.
Kit
The present invention also provides a kind of kits for predicting metabolic syndrome risk.Kit for use in the present invention
Generally include the overlength chain saturated fatty acid standard items and/or metabolic syndrome risk judgment of detection reagent, various concentration
Specification.
Wherein, detection method is described in the specification and according to different sample measurements A1Judge Metabolic syndrome
Levy the related description of risk.
A kind of typical kit of the invention can be used for detecting human blood sample, plasma sample.
It should be understood that the invention firstly discloses specific overlength chain saturated fatty acid of the invention and metabolic syndromes
After the correlation of risk, it is pre- that those skilled in the art carry out early stage to metabolic syndrome according to above-mentioned correlation with can be convenient
It surveys or the dietary supplements or its food or its related drugs of overlength chain saturated fatty acid is taken in Disease Intervention or guidance.
Main advantages of the present invention include:
(1) present invention firstly discovers that blood plasma overlength chain saturated fatty acid and metabolic syndrome prevalence risk are significant negative pass
Connection.
(2) present invention analyze for the first time the relationship and fatty acid of blood plasma overlength chain saturated fatty acid and metabolic syndrome with
The reciprocation of the risk factors such as age, movement, hypertension.
(3) present invention firstly discovers that plasma C 20:There are significant interactions for 0 horizontal and gender and situation of drinking, and drink
It is the risk factor of metabolic syndrome, thus speculates, for the crowd of long-term heavy drinking, it is contemplated that meal supplement C20:0 or
Corresponding replenishers are taken, its risk for suffering from metabolic syndrome is reduced.
(4) present invention firstly discovers that overlength chain saturated fatty acid is reduced as metabolic syndrome scores and reduced.
(5) on the one hand discovery for the first time of the invention can be used to predict metabolic syndrome risk, on the other hand, pass through diet
Strengthen over-long chain fatty acid or take over-long chain fatty acid replenishers, early prediction is carried out to metabolic syndrome or disease is dry
In advance.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part, such as Sambrook et al., molecular cloning:Laboratory manual (New York:Cold Spring Harbor
Laboratory Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.Unless otherwise stated, no
Then percentage and number are weight percent and parts by weight.
Unless otherwise instructed, otherwise material used in description of the invention and reagent are commercial product.
1. respondent
In 2 years chase experiment, the fatty acid of the baseline for the resident that 2008 stay in Beijing Shunyi, blood are had detected
Rouge, blood glucose, blood pressure, waistline, height and weight, and the living habits information such as smoking is had collected, drinks, move, excluding data
Missing, exclusion has cardiovascular disease, malignant tumour, and has the people of other major diseases, is finally analyzed using 1729 people
The relationship of blood overlength chain saturated fatty acid and metabolic syndrome.
2. Ethic review
The Institutional Review Board of National Center for Chronic and Noncommunicable Disease Control and Prevention.
3. the step of specific experiment
3.1 collect crowd's blood sample, detect blood total cholesterol, triglycerides, high-density lipoprotein, fasting blood-glucose etc.
Index.
3.2 detection fatty acid:Gas-chromatography (GC)-hydrogen flame ion is used after esterification after Folch method extraction fatty acid
Change detection (FID) method measurement fatty acid composition and content.
Bis- peanut docosahexaenoyl-sn-glycero -3- phosphocholine (1,2- of 1,2- is added into 100ul blood plasma
Dihenarachidoyl-sn-glycero-3-phosphocholine it) is used as internal standard, extracts lipid with methylene chloride/methanol,
By solvent by being dried with nitrogen, fatty acid methyl is carried out with methanol/sulfuric acid, FAMEs. is generated with n-hexane and extracts FAMEs, it will
Solvent, which passes through, to be dried with nitrogen, then is dissolved with isooctane.It is detected with Agilent 6890GC/FID, chromatographic column is
Supelco SP-2560 (100m*0.25mm inside diameter*0.20um thickness), is as a result expressed as weight
Percentage.
The definition of 3.3 metabolic syndromes:The international newest metabolic syndrome diagnostic criteria of diabetes association, for metabolic syndrome
It is sampled:In addition three or three or more in following five factors:
● central obesity:Waistline >=90cm (male), waistline >=80cm (female)
● triglycerides:>=1.7mmol/L or the special treatment for receiving to adjust blood lipid
● high-density lipoprotein:<1.03mmol/L (male) and<1.29mmol/L (female) or the spy for receiving to adjust blood lipid
Different treatment
● blood pressure:Systolic pressure >=130mm Hg or diastolic pressure >=85mm Hg are taking antihypertensive drugs
● fasting blood-glucose:>=100mg/dL (5.6mmol/L) is diagnosed as type II diabetes before
The analysis of 3.5 data:Rank sum test and Chi-square Test are respectively intended to the difference of the basic variable between three kinds of genotype of detection
It is different.Logistic, which is returned, is used to being associated with for blood plasma overlength chain saturated fatty acid and metabolic syndrome risk.In addition, we also utilize
Generalized linear regression analyzes relationship and fatty acid and the age, fortune of blood plasma overlength chain saturated fatty acid and metabolic syndrome
The reciprocation of the risk factors such as dynamic, hypertension.
4 experimental results
4.1 blood plasma overlength chain saturated fatty acids and metabolic syndrome risk
The blood plasma overlength chain saturated fatty acid and metabolic syndrome prevalence risk of High plasma levels have significant negative customers.ORs
(odds ratio, odds ratios) value is C20:0,0.18 (0.13,0.25);C22:0,0.26 (0.18,0.35);C24:0,
0.19(0.13,0.26);Total overlength chain saturated fatty acid 0.16 (0.11,0.22).(Fig. 1)
The relationship of 4.2 blood plasma overlength chain saturated fatty acids and Metabolic syndrome scoring
Blood plasma overlength chain saturated fatty acid level linear reduction (Fig. 2) with the increase that Metabolic syndrome scores.With metabolism
Comprehensive score≤2,3,4,5, blood plasma overlength chain saturated fatty acid level is respectively (being expressed as median (Q1-Q4)):
C20:0:0.18(0.20-0.23),0.16(0.18-0.20),0.15(0.17-0.20),0.15(0.17-0.20)
C22:0:0.59(0.70-0.84),0.47(0.59-0.70),0.56(0.67-0.79),0.51(0.62-0.71)
C24:0:0.46(0.61-0.73),0.47(0.57-0.68),0.26(0.34-0.46),0.26(0.34-0.43)
The reciprocation of 4.3 blood plasma overlength chain saturated fatty acids and other factors
Plasma C 20:There are significant interactions for 0 horizontal and gender and situation of drinking.P value<0.01.(see Fig. 3)
5. experiment conclusion
Result of study of the invention shows that blood plasma overlength chain saturated fatty acid and metabolic syndrome have significant negative customers.And
And overlength chain saturated fatty acid is reduced as metabolic syndrome scores and is reduced.That is, if full using blood plasma overlength chain
Metabolic syndrome is predicted with fatty acid, concentration is lower, and the severity of metabolic syndrome may be higher.In layering point
In analysis, C20 is found:0 level has reciprocation with drinking, and drinking is the risk factor of metabolic syndrome, is thus speculated, right
In the crowd of long-term heavy drinking, it is contemplated that meal supplement C20:0 or corresponding replenishers are taken, reduces it and suffer from metabolic syndrome
Risk.
In conclusion discovery prompt blood plasma over-long chain fatty acid of the invention is horizontal, on the one hand can be used to predict to be metabolized
On the other hand syndrome risk strengthens over-long chain fatty acid by diet or takes over-long chain fatty acid replenishers, to metabolism
Syndrome carries out early prediction or Disease Intervention.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To make various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (10)
1. the purposes of a kind of overlength chain saturated fatty acid or its detection reagent, which is characterized in that it is used to prepare a kit, it is described
Kit is for detecting metabolic syndrome neurological susceptibility or its risk;
Wherein, the overlength chain saturated fatty acid is the overlength chain saturated fatty acid of carbon atom number >=20.
2. purposes as described in claim 1, which is characterized in that the carbon atom number of the overlength chain saturated fatty acid is 20-24,
Preferably 20-23.
3. purposes as described in claim 1, which is characterized in that the overlength chain saturated fatty acid is selected from the group:C20:0,
C22:0,C23:0,C24:0, or combinations thereof.
4. purposes as described in claim 1, which is characterized in that described is detected as blood testing, blood plasma detection or serum inspection
It surveys.
5. purposes as described in claim 1, which is characterized in that the detection is a certain of the sample of self-test in future object
Compared with overlength chain saturated fatty acid content A1 overlength chain saturated fatty acid content A0 corresponding with normal population, if A1 is significantly high
In A0, then prompt the neurological susceptibility of the metabolic syndrome of test object lower.
6. purposes as described in claim 1, which is characterized in that the detection reagent includes Mass Spectrometer Method reagent.
7. a kind of for detecting the kit of metabolic syndrome risk, which is characterized in that including:
(a) reagent for overlength chain saturated fatty acid content in test sample, wherein the sample includes blood sample, blood plasma
Sample or blood serum sample, the overlength chain saturated fatty acid include the overlength chain saturated fatty acid of carbon atom number >=20;
(b) overlength chain saturated fatty acid standard items;
(c) operation instructions.
8. a kind of method for detecting metabolic syndrome risk, which is characterized in that including step:
(a) test sample of subject is provided;
(b) content for measuring overlength chain saturated fatty acid in the sample is A1;
(c) step (b) is compared with the overlength chain saturated fatty acid content A0 of normal population sample, if A1 is significantly higher than A0,
Then illustrate that the risk of test group metabolic syndrome is lower;
Wherein, the overlength chain saturated fatty acid is the overlength chain saturated fatty acid of carbon atom number >=20.
9. a kind of method for producing ready-mixed oil, which is characterized in that including step:
(i) substrate oil is provided;
(ii) content of overlength chain saturated fatty acid in the substrate oil is detected, wherein the overlength chain saturated fatty acid
Carbon atom number >=20;With
(iii) content based on overlength chain saturated fatty acid described in step (iii) adds predetermined content into the substrate oil
Overlength chain saturated fatty acid, to obtain the ready-mixed oil.
10. method as claimed in claim 9, which is characterized in that total restatement that the predetermined content refers to the ready-mixed oil,
The additive amount of the overlength chain saturated fatty acid is 0.5-20%, preferably, 1-15%, more preferably, 2-10%.
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