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[(c)-3.1(l)-3.6(e)-3.1(s)-200(would)-204.4(r)-3.4(em)-5.5(ai)-3.9(n)-204(i)1.2(n)-204(t)-3.3(he)-204.9(he)-3.1(ar)-3.4(t)-205.1(o)3.3(r)-205.2(r)-3.4(et)-3.3(ur)-3.4(n)-198.9(t)-3.3(o)-198.5(t)-3.3(he)-204.9(ci)-3.9(r)-3.4(c)2(ul)-3.6(ati)-3.9(o)-1.9(n;)]TJ
0 -1.1847 TD
-.0187 Tc
[(and)-440.2(w)1.3(heth)5.3(er)-441(a)-440.4(s)-1.3(ingle)-440.8(d)-.5(ose)-445.9(o)5.4(f)]TJ
/F14 1 Tf
12.2604 0 TD
-.0175 Tc
[(Ma)5.9(p4k4)]TJ
/F10 1 Tf
3.1349 0 TD
-.0182 Tc
[(-)4.7(d)0(ire)4.6(c)-.5(ted)-439.7(s)4.4(iRNA)]TJ
-15.3954 -1.1795 TD
-.0188 Tc
[(could)-430(m)1.7(odify)-424.7(M)2.3(/M)-421.9(secretory)-429.9(p)]TJ
12.5036 0 TD
-.018 Tc
[(roles)-424.8(acro)6.1(ss)-424.8(the)-424.5(e)-.3(n)5.7(t)-.5(ir)4.6(e)]TJ
-12.5036 -1.1847 TD
-.0188 Tc
[(myocardium,)-204.3(r)-1.4(eco)5.3(gnizing)-202.3(t)-1.3(hat)-203.1(o).1(nly)-207.4(a)-202.6(fraction)-207.2(of)-203.7(th)5.2(e)-208.1(i)-1.9(ntra-)]TJ
0 -1.1795 TD
[(cardiac)-301.1(M)2.4(/M)-297.7(pop)4.7(u)-.5(lation)-300.2(wou)4.7(l)-1.5(d)-300.5(t)-1.2(a)4.4(k)-.5(e)-301.1(u)-.5(p)-300.5(p)-.5(a)4.4(r)-1.3(ticles.)]TJ
/F7 1 Tf
10.4607 0 0 10.4607 59.7543 128.0126 Tm
/Cs8 cs 1 scn
0 Tc
(Methods)Tj
/F11 1 Tf
0 -1.2411 TD
(Animals)Tj
/F10 1 Tf
10.959 0 0 10.959 59.7543 102.1039 Tm
0 0 0 rg
[(Animal)-401.5(protocols)-396.7(were)-398(approved)-398.4(by)-397.4(the)-401.3(Institutiona)6.1(l)]TJ
0 -1.1847 TD
[(Animal)-396.3(Care)-392.9(and)-395.4(Use)-389.6(Committee)-392(under)-396.3(NIH)-392.5(guide-)]TJ
0 -1.1795 TD
[(lines.)-475.5(C57BL/6J)-468.7(mice,)-469.8(age)-473.8(79)-466.8(weeks,)-472.2(2026)-165.8(g,)-472.4(were)]TJ
0 -1.1847 TD
[(purchased)-304.1(from)-298.9(Jackson)-298.8(Laboratory.)]TJ
/F11 1 Tf
10.4607 0 0 10.4607 310.8472 698.2297 Tm
/Cs8 cs 1 scn
(Particles)Tj
/F10 1 Tf
10.959 0 0 10.959 310.8472 685.2471 Tm
0 0 0 rg
[(GeRPs)-471(were)-475.6(prepared)-472.9(as)-476.8(described)-471.2(previously.)]TJ
8.2191 0 0 7.3052 523.1053 690.1227 Tm
(47)Tj
10.959 0 0 10.959 540.34 685.2471 Tm
(In)Tj
-20.941 -1.1795 TD
[(brief,)-253.1(hollow)-256.3(glucan)-254.3(shells,)-255.7(24)]TJ
/F8 1 Tf
12.4208 0 TD
(l)Tj
/F10 1 Tf
.5535 0 TD
[(m)-253.7(diameter,)-253.9(produced)]TJ
-12.9743 -1.1847 TD
(from)Tj
/F14 1 Tf
2.3124 0 TD
[(Saccharomyces)-348.5(cerevisiae)]TJ
/F10 1 Tf
10.2687 0 TD
[(cell)-349.3(walls,)-349.2(were)-346.3(labeled)]TJ
-12.5812 -1.1795 TD
[(with)-263.1(5-DTAF)-259([5-\(4,)-262(6-dichlorotriazinyl\))-260.1(aminouores-)]TJ
0 -1.1847 TD
[(cein;)-580.4(ThermoFisher].)-580.8(For)-581.8(siRNA)-579.6(loading,)-582.1(10)]TJ
/F8 1 Tf
19.3632 0 TD
(l)Tj
/F10 1 Tf
.5484 0 TD
.5812 Tc
[(Lo)581.2(f)]TJ
-19.9115 -1.1795 TD
0 Tc
[(1)-157.3(m)15.3(M)-294.5(s)12.2(i)11.7(R)0(N)18.3(A)-290.7(we)22.1(re)-285.7(c)12.5(o)0(m)18.7(b)13.7(in)19.8(ed)-284.9(w)14.8(i)0(t)18.8(h)-291.5(85)]TJ
/F8 1 Tf
14.9763 0 TD
(l)Tj
/F10 1 Tf
.5432 0 TD
[(L)-291.5(o)13.7(f)-293.6(s)12.2(od)16.4(i)11.7(u)0(m)-282(a)12.8(c-)]TJ
-15.5195 -1.1795 TD
[(e)12.5(t)0(a)19.9(t)0(e)-192.5(\()0(3)20.2(0)-157.3(m)10.2(M)10.7(\))11.9(,)-206.2(t)12.3(h)0(e)21(n)-203.9(ad)20.6(de)20.3(d)-204.2(t)12.3(o)-203.6(9)0(4)]TJ
/F8 1 Tf
12.5398 0 TD
(l)Tj
/F10 1 Tf
.538 0 TD
[(L)-203.6(o)0(f)-191.9(5)-157.3(m)10.2(M)-201.4(En)21.8(do)21.6(po)16.4(r)12.2(t)12.3(er)]TJ
-13.0778 -1.1847 TD
[(\()11.9(G)0(e)16.9(n)13.3(e)-375.5(T)0(o)22.5(o)0(l)20.6(s)0(\))19(,)-376.9(a)12.8(n)0(d)-366.8(i)11.7(nc)20.6(ub)21.6(at)19.9(ed)-367.6(a)12.8(t)-375.7(r)12.2(o)0(o)22.3(m)-377.8(t)12.3(e)12.5(m)10.2(p)0(e)15.2(r)12.2(a)12.8(t)0(u)20.2(r)0(e)-368.5(f)11.7(or)]TJ
0 -1.1795 TD
[(1)13.4(5)-157.3(m)10.2(i)11.7(n.)-260.1(Te)21.2(n)-271.2(m)10.2(i)11.7(l)0(l)18.9(i)11.7(gr)20.1(am)17.8(s)-267.1(o)0(f)-259.2(g)0(l)20(u)13(ca)14.9(n)-266(s)0(h)20.7(e)0(l)19.3(l)12(s)-272.3(w)14.8(er)19.5(e)-272(a)12.8(dd)15.7(e)12.5(d)0(,)-260.4(i)11.7(n-)]TJ
0 -1.1847 TD
[(c)12.5(u)0(b)21.6(a)0(t)19.9(e)0(d)-196.9(f)0(o)20.2(r)-210.2(1)-152.1(h)-208.8(at)-197.3(r)12.2(o)0(o)22.3(m)-207.1(te)19.6(m)10.2(p)0(e)20.3(r)0(a)19.9(t)0(u)20.1(r)0(e)19.5(,)-206.2(an)15.8(d)-204.2(t)12.3(he)15.8(n)-203.9(d)0(i)19.5(l)12(ut)20.1(ed)-196.9(in)]TJ
0 -1.1795 TD
[(p)13(h)0(o)17.1(s)12.2(ph)21.5(at)19.9(e-)19.9(bu)21.6(ff)18.1(er)19.5(ed)-548.7(s)12.2(a)0(l)19.6(i)11.7(ne)-548.4(\(P)20.4(BS)21.5(\))-557.1(t)0(o)-548.2(1)0(.)19.3(5)-157.3(m)15.3(L)0(.)-549.5(P)0(a)21.3(r)0(t)19.3(i)11.7(cl)19.4(es)]TJ
0 -1.1847 TD
[(we)22.1(re)-337.4(s)12.2(t)0(o)20.8(r)0(e)19.5(d)-349.1(a)12.8(t)]TJ
/F15 1 Tf
6.0216 0 TD
()Tj
/F10 1 Tf
.7708 0 TD
(80)Tj
/F12 1 Tf
.9363 0 TD
()Tj
/F10 1 Tf
.388 0 TD
[(C)-342.4(a)0(n)21(d)-349.1(s)12.2(o)0(n)21.9(i)0(c)19(a)0(t)19.9(e)0(d)-336.6(b)0(e)21(f)11.7(or)15.6(e)-344.5(u)13(se)19.5(.)-345.9(H)0(e)17.2(a)12.8(rt)]TJ
-8.1167 -1.1795 TD
[(i)11.7(n)0(j)20.2(e)0(c)19.8(t)12.3(at)19.9(es)-575.4(o)13.7(f)-583.3(em)17.5(p)13(t)0(y)-574.7(p)13(ar)19.8(ti)18.8(cl)19.3(e)12.5(s)-582.7(\(n)14.9(o)-581.2(s)12.2(i)11.7(R)0(N)18.3(A)0(\))-573.7(u)13(ti)18.8(l)12(i)0(z)19(e)0(d)-574.6(a)]TJ
0 -1.1847 TD
-.0134 Tc
[(do)-13.4(s)7.4(e)-580.3(of)-581.1(2.)-13.4(7)]TJ
/F12 1 Tf
4.9869 0 TD
0 Tc
()Tj
/F10 1 Tf
.7087 0 TD
(10)Tj
8.2191 0 0 7.3052 383.5274 521.7448 Tm
(8)Tj
/F8 1 Tf
10.959 0 0 10.959 393.6755 516.8691 Tm
(b)Tj
/F10 1 Tf
.538 0 TD
[(-g)20.5(lu)19.9(ca)20.1(n)-566.1(s)12.2(he)15.8(l)12(l)12(s)0(/)18.7(h)0(e)21(a)0(r)19.8(t)0(.)-556(I)12.3(nj)20.2(ec)19.8(ta)19.9(te)19.6(s)-562(o)0(f)]TJ
-8.096 -1.1795 TD
[(s)12.2(i)0(R)20.4(N)0(A)18.9(-)12.6(lo)20.6(ad)20.6(ed)-424.5(p)13(a)0(r)19.8(t)0(i)18.8(c)0(l)19.3(e)12.5(s)-432.7(c)12.5(on)16.7(s)12.2(i)11.7(st)19.3(ed)-424.6(o)13.7(f)-433.2(5)]TJ
/F12 1 Tf
15.535 0 TD
()Tj
/F10 1 Tf
.7087 0 TD
(10)Tj
8.2191 0 0 7.3052 499.1243 508.8188 Tm
(7)Tj
10.959 0 0 10.959 507.7983 503.9432 Tm
[(Ge)22.1(RP)17.2(s)-427.5(i)0(n)]TJ
-17.9716 -1.1847 TD
-.0134 Tc
(10)Tj
/F8 1 Tf
1.1019 0 TD
0 Tc
(l)Tj
/F10 1 Tf
.5432 0 TD
[(L)-358.8(P)13.6(BS)16.4(,)-356.2(c)0(o)21(n)0(t)20.5(a)0(i)19.3(n)0(i)19.8(n)0(g)-346(5)0(0)-149.1(p)13(m)10.2(o)0(l)]TJ
/F14 1 Tf
11.0809 0 TD
-.0128 Tc
[(Ma)-12.8(p4k)-12.8(4)]TJ
/F10 1 Tf
3.5591 0 TD
0 Tc
[(s)12.2(i)11.7(RN)18.3(A,)-346.9(ca)20.1(lc)19.3(u-)]TJ
-16.2851 -1.1795 TD
[(l)12(a)0(t)19.9(e)0(d)-667.7(t)12.3(o)-674.3(p)0(r)20.1(o)0(v)16.5(i)11.7(de)-667.7(1)13.4(0)-674.6(Ge)16.9(R)13.9(P)0(s)15.5(/)11.6(m)10.2(a)12.8(cr)19.5(op)16.4(h)13.7(a)0(g)20.7(e)0(,)-669.6(b)13.7(as)19.8(ed)-667.7(on)]TJ
T*
(4)Tj
/F12 1 Tf
.6363 0 TD
()Tj
/F10 1 Tf
.7036 0 TD
(10)Tj
8.2191 0 0 7.3052 335.792 469.9274 Tm
(6)Tj
10.959 0 0 10.959 344.1259 465.1085 Tm
[(F4)21.3(/)11.6(8)0(0)]TJ
/F12 1 Tf
8.2191 0 0 7.3052 368.5605 469.9274 Tm
(+)Tj
/F10 1 Tf
10.959 0 0 10.959 377.4613 465.1085 Tm
[(m)10.2(a)12.8(cr)19.5(op)21.6(ha)21.3(ge)20.4(s/)18.7(he)21(ar)19.8(t)-401.6(m)10.2(e)12.5(a)0(s)19.8(u)0(r)20.1(e)0(d)-388.3(o)0(n)-386.8(d)0(a)20.7(y)-400.7(2)]TJ
-6.0785 -1.1847 TD
-.0202 Tc
[(p)-7.2(o)-20.2(st)-20.2(in)-20.2(fa)-20.2(rc)-20.2(ti)-8.5(o)-20.2(n)-3.5(.)-495.4(T)-20.2(he)]TJ
/F14 1 Tf
8.1684 0 TD
0 Tc
[(M)11.1(a)13.1(p4)21(k4)]TJ
/F10 1 Tf
3.6678 0 TD
[(si)18.7(RN)18.3(A)-471.8(s)0(e)19.5(q)0(u)16(e)12.5(nc)20.6(e)-479(u)13(ti)18.8(l)12(i)0(z)19(e)0(d)]TJ
-11.8362 -1.1795 TD
[(wa)22.5(s)-608.6(5)]TJ
/F12 1 Tf
2.5349 0 TD
()Tj
/F10 1 Tf
.238 0 TD
[(-)12.6(G)0(A)18.9(C)0(C)23.9(A)0(A)18.6(C)0(U)19.3(C)14.5(UG)19.5(GC)19(U)15.1(U)0(G)19.5(U)0(U)19.8(A)0(U)24.4(U)0(-)17.3(3)]TJ
/F12 1 Tf
15.623 0 TD
()Tj
/F10 1 Tf
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.6045 Tc
[(,a)604.5(c)624.6(c)604.5(e)624.3(s)604.5(-)]TJ
-18.6389 -1.1847 TD
-.0203 Tc
[(s)-8.1(i)-20.3(on)-312.2(n)-7(u)-20.3(mb)-20.3(er)-313.3(N)-5.5(M)-9.6(_)-20.3(0)-3.5(0)-6.9(8)-20.3(69)-20.3(6.)-20.3(2.)]TJ
8.2191 0 0 7.3052 432.5668 431.0928 Tm
0 Tc
(4)Tj
/F11 1 Tf
10.4607 0 0 10.4607 310.8472 400.1385 Tm
/Cs8 cs 1 scn
[(Myocardial)-297.9(infarction)]TJ
0 -1.2357 TD
[(and)-298.4(intramyocardial)-297.7(injections)]TJ
/F10 1 Tf
10.959 0 0 10.959 310.8472 374.2298 Tm
0 0 0 rg
[(Under)-389.1(isourane)-386.7(anesthesia)-391.3(with)-387.2(mechanical)-388.2(ventila-)]TJ
0 -1.1795 TD
[(tion,)-470.7(AMIs)-467.6(were)-470.5(created)-470.9(through)-467(left)-468.9(thoracotomies)]TJ
0 -1.1847 TD
[(by)-325(left)-324(anterior)-323.4(descending)-322.9(coronary)-325.8(ligation)-323.6(\(without)]TJ
0 -1.1795 TD
[(reperfusion\).)-206.3(Five)-203.2(minutes)-204.5(later,)-201.3(a)-204.5(single)-204.5(10)]TJ
/F8 1 Tf
17.0456 0 TD
(l)Tj
/F10 1 Tf
.5535 0 TD
[(L)-203.6(injection)]TJ
-17.5991 -1.1847 TD
[(of)-414.4(PBS,)-409(empty)-414.9(GeRPs)-414.1(\(no)-411.1(siRNA\),)-411.8(or)-413.8(siRNA-loaded)]TJ
0 -1.1795 TD
[(GeRPs)-305.4(was)-301.6(made)-308.5(directly)-304.2(into)-305.9(the)-303(infarct)-306.7(center)-307.5(using)]TJ
T*
.0094 Tc
[(a)-510.6(3)-3.1(0G)-513.8(needle.)-517.5(A)3.2(t)-516.3(t)1(e)-4(r).9(minal)-511.4(s)-4.2(urgery,)-512.4(m)-1.1(ic)-4(e)-510.9(w)-1.6(ere)-516.1(r).9(e)-4(-)]TJ
0 -1.1847 TD
[(anest)-4.2(h)2.4(et)-4.2(ize)-4(d)-298.3(with)-302.8(isourane)-298.8(f).4(or)-299.1(ti)-4.8(ssue)-298.8(c)1.2(olle)-4(ction.)]TJ
/F11 1 Tf
10.4607 0 0 10.4607 310.8472 257.4991 Tm
/Cs8 cs 1 scn
0 Tc
[(Flow)-298.2(cytometry)]TJ
/F10 1 Tf
10.959 0 0 10.959 310.8472 244.5731 Tm
0 0 0 rg
[(After)-438.7(heparinization,)-437.7(peripheral)-438.2(blood,)-440(spleen,)-441(heart,)]TJ
T*
[(and)-323(femurs)-326.6(were)-325.6(collected.)-326(Hearts)-326.4(were)-325.6(perfused)-324.1(with)]TJ
0 -1.1795 TD
.1625 Tc
[(2m)162.5(L)-160.3(4)]TJ
/F12 1 Tf
2.7832 0 TD
0 Tc
()Tj
/F10 1 Tf
.3983 0 TD
[(C)-321.7(St.)-320.8(Thomas)-321.2(cardioplegia)-319.7(solution,)-321.5(atria)-321(dis-)]TJ
-3.1815 -1.1847 TD
[(carded,)-554.4(and)-555.8(the)-551.3(entire)-556.6(ventricle)-555.2(minced,)-552.1(then)-553.5(sus-)]TJ
0 -1.1795 TD
[(pended)-708.9(in)-709.6(810)-163.7(mL)-710.8(lysis)-709.5(buffer)-706.4(\(10)-168.2(mM)-708.5(HEPES,)]TJ
0 -1.1847 TD
[(30)-164.6(mM)-361.9(taurine,)-366.7(and)-364.4(0.2)-163.9(mg/mL)-365.5(Liberase)-364.3(TH)-364.2(protease)]TJ
0 -1.1795 TD
[(cocktail)-349.5([Roche])-354.8(in)-352.6(HBSS)-349([1)]TJ
/F12 1 Tf
11.7069 0 TD
()Tj
/F10 1 Tf
.7191 0 TD
[(]\).)-353.1(The)-353.1(suspension)-353.9(was)]TJ
-12.426 -1.1795 TD
[(ltered)-273.9(\(40)]TJ
/F8 1 Tf
4.5369 0 TD
(l)Tj
/F10 1 Tf
.5535 0 TD
-.0001 Tc
[(m)-274.5(strainer\))-276.9(into)-275(digestion-stopping)-277.6(buffer)]TJ
-5.0904 -1.1847 TD
0 Tc
[(\(10)-163(mM)-201.6(HEPES,)-199.6(30)-164.6(mM)-201.6(taurin)8.1(e,)-204.1(diluted)-197(1:10)-202.2(with)-201(heat-)]TJ
0 -1.1795 TD
[(inactiv)9.8(ated)-254.6(fetal)-254.3(bovine)-253(serum\).)-253.2(Spleen)-255(tissue)-257.1(and)-255.7(bone)]TJ
0 -1.1847 TD
[(marro)9.4(w)-605.9(were)-605(simila)8.5(rly)-604.1(ltered.)-599.1(Heart,)-601.8(spleen,)-601.4(and)]TJ
0 -1.1795 TD
[(marro)9.4(w-isolat)9(ed)-419.4(cells)-409.5(were)-413.6(pellete)9.2(d)-416.3(b)0(y)-418.1(centri)7.2(fugation)]TJ
0 -1.1847 TD
[(\(5)-160.9(min,)-429.7(1000)]TJ
/F12 1 Tf
5.318 0 TD
()Tj
/F14 1 Tf
.7191 0 TD
(g)Tj
/F10 1 Tf
.4139 0 TD
.4286 Tc
(,4)Tj
/F12 1 Tf
1.1278 0 TD
0 Tc
()Tj
/F10 1 Tf
.3932 0 TD
[(C\),)-428.1(incubate)8.7(d)-431.9(i)0(n)-425(erythroc)9.1(yte)-427.7(lysis)]TJ
-7.9719 -1.1795 TD
[(buffer)-473.6(\(BioLeg)7.7(end\),)-481.4(re-pel)7.6(leted)-475.7(and)-483.3(washe)9.1(d)-483.6(i)0(n)-476.8(1)-167.6(mL)]TJ
0 -1.1847 TD
[(cell)-763.1(staining)-763.5(buffer)-763.3(\(BioLeg)7.8(end\),)-765.9(centrifu)6.1(ged)-768.4(and)]TJ
/F11 1 Tf
7.9702 0 0 7.9702 59.7543 755.2061 Tm
(Luo,)Tj
/F16 1 Tf
2.0486 0 TD
[(et)-300.9(al.;)-297.1(BioResearch)-295.1(Open)-297.2(Access)]TJ
/F11 1 Tf
12.9317 0 TD
[(2020,)-302.4(9.1)]TJ
-14.9803 -1.2021 TD
[(http://online)10(.liebertpub.com)7(/doi/10.10)9.8(89/biores.202)9.6(0.0037)]TJ
59.978 1.2021 TD
(259)Tj
ET
/EmbeddedDocument /MC5 BDC
/Document /MC6 BDC
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1 i
572.031 35.263 10.035 -19.162 re
W n
.55686 .047059 .22745 rg
q 1 0 0 1 572.031 16.06 cm 0 0 m
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1.739 4.818 2.425 6.378 3.087 7.332 c
3.497 7.924 4.368 8.916 4.541 9.195 c
4.633 9.338 4.701 9.556 y
4.901 9.641 5.09 9.748 v
5.279 9.855 5.638 10.053 5.702 10.239 c
5.807 10.549 5.997 10.624 y
6.187 10.665 6.271 10.678 v
6.44 10.699 6.566 10.772 6.735 10.858 c
6.904 10.945 7.12 11.061 7.516 11.253 c
7.799 11.391 10.08 12.245 y
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