免费文献传递   相关文献

Molecular mechanism of rhein on inhibiting autophagic protein expression in renal tubular epithelial cells via regulating mTOR signaling pathway activation

大黄酸调控mTOR信号通路活性抑制肾小管上皮细胞自噬蛋白表达的分子机制



全 文 :—˜™†š
/CB>
kžŸ ¡¢£¤¥¦§¨©•–
56

!
(
!*
!
!
;7<
)
!
!#
!&
!
9:

!
78

e
~ìPdkbc lmnop
!
}š ~ì
*$$*4%
*e
}šqPde ~ìPdkbc fgde lrj
!
}š ~ì
*$$*4%
)eKDIGYW/D1W.X9.ZD-[ZGY8US1GZU1S! A1UaDYVUW6.XRG/G1GVTU! ]GIG1 RG/G1GVTU&$45)(4(%
&e
~ìbc dce fghide Pdj
!
}š ~ì
*$$$(#

tu
#!

#
Âט™œ–êëzûx:žŸ
!;>@5*?
 ¡¢£¤¥’“”¨©•–
)
Ž
#
“
MG1_fV
è½xvY
!MG1_fVOGZG1-DH VGZWV.Z[WU.1$M\88

;>@5*?
 ¡aåêëK‰
$
“ŽémPÝ
!$$$e$$*$# T$
Û
F
$
=Ë ¡¢£I.w¤¥
,,,
ìâ{|Ùí|\;3¤¥


)!/U-Y.W[O[ZD5GVV.-UGWDH IY.WDU1 ZUSTW-TGU1 )$N<):=
:
¦§çè
&

$
=Ë ¡ìâ{|Ü­îÀ¬ï¤¥
!/G//GZUG1 WGYSDW.XYGIG/6-U1$/CB>
¦§É$ٙ‘çè
!IT.V5
IT.Y6ZGWDH5/CB>8DY*&&($I5/CB>8*&&(&
Ãé
$
½—˜™
! /S-N
h
%M\88! /N
½É
/CB>
œ–Ò­îÀ¬
!$$ 1/.Z-
N
h

ÿðÐÆ)Ž
$
¨Â=Ë$
N<) :=:$/CB>$I5/CB>8*&&(
¤¥¦§ç胑
)

#M\88

;>@5*?
 ¡
N<)
:
¤¥‰¦§
%I5/CB>8*&&(
¤¥¦§
&
—˜™S
M\88
Æ)ŽÖ½ã–
M\88
zû
;>@5*?
 ¡
N<) :
”
I5/CB>
8*&&(
¤¥¦§çè
&
­îÀ¬S—˜™
%M\88
Æ)ŽÖ½ÚŸ
M\88
zû
;>@5*?
 ¡
N<) :
¤¥¦§çè
)
‘
#
M\88
œ–
/CB>
k&
—˜™†š
/CB>
k£¤¥¦§
$
¶Ö=ů$Ž ¡¢£’“”¨©•–
)

vwx
#!
—˜™
&
¢£
&/CB>
k&
x:žŸ ¡
&
­îÀ¬

yz)(
#!*$&5$%5*#

{|}L
#!
%ë¢Ã&6ìížîà
!()%)#$%&
àá‰âß
ã&Ïäòöîà

~€
#!
!
óô
$
õ$Bö
$
÷ø
$
ùúåûö
$CDZ#!$*
(##%&54$)$$?5/GUZ#0VV[1+DU2#)e-./

€‚ƒ
#!
ñò
$
ùúàáå
$?5/GUZ#W[6[DW[6[D2#)e-./
!!
¢£
!G[W.ITGS6
¯Yó ¡8¬Çv5ôÝ
Þw¤¥‡-õö
$
‚¨®é¢£
!/G-Y.G[W.IT5
GS6%
\¢£
!/U-Y.G[W.ITGS6
”¨©(ôÈûw¢
£
!-TGIDY.15/DHUGWDH G[W.ITGS6$<93$
$$
$
é¢
£
!
õn®¢£

“ ¡8s®ËÌ
*+
)
àá¦
…
**5)+
$
¢£“êë
%
“¼
%
“)
=
€Ä#”œÕÁë
›tÖl¾›
$
JK
$
“b ¡8NõÌ
%
†š
=ÕQyÁÍíb×M|‚’“
)
ìâ{|­îÀ
¬ï¤¥
!/G//GZUG1 WGYSDW.XYGIG/6-U1$/CB>
Ö
½†š ¡arÉ$äW”OPõö
$
ÙP
$
’®¢
£‚†‡Ò
$
Í=ߜ– ¡¢£
*&+
)
ô
$
tÔx:žŸ ¡´Ú
$
“åï”zïë›t
$
¢
£t$’“áö¯÷ë
B
¯øÖ½lBCžø“


Æx
(
$,ЭîÀ¬/éê
B
àí‘د—
…Ü
*+
)
¸`´
*#+
$
¢£SOPoCM¦KÆP
)
ÑÒ㾿zûxŽ‘}~æ
$
ŒUbÈ
$
—˜„©…
!
.—˜
%
„©
%
 ù±È

Ö½Aõ†
š
];@=\-Z5*
k¡OP”xŽ‘
*%+
)
’®—˜„©…ù,
o¬—˜
$
$‚Ȩ
,,,
—˜™
!YTDU1
“ô8
”Ö½†‡x:žŸ ¡–¨‘
$
ˆ‰x
‘
*(54+
$
$%
$
—˜™¯ø“ô”Ö½éêx:ž
Ÿ ¡¢£
$
JAõ
/CB>
k“ú
B
ŒU͓
MG1_fV
è½xvY
!MG1_fVOGZ5
G1-DH VGZWV.Z[WU.1$M\88
zû—æx:žŸ
!;>@5*?
 ¡êëK‰´¾›$¢£
$
S­îÀ
¬;tÑ
$
öfą—˜™Aõ
/CB>
k
;>@5*?
 ¡¢£’“”¨©•–
)
!
ÊûSÍÎ
b!
,|SöÒ
!
—˜™
!
“
$e /.Z-N
h
;GBM
I+È
S-N
h
vY
%
­îÀ¬
!
“¨ˆ6™ûI
-$4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&

$$
!
/.Z-N
h
vY

ú¢m%
8US/G53ZHYU-T
EF
&K[ZOD--.fV9.HUXUDH ?GSZD9DHU[/=;[WYUD1W
9U7W[YDE5*!K9?9=E*
&6
%
üö)*
!EDWGZ
O.aU1DVDY[/$E\8%
ðÀ¬÷À¬vY
%MG1_fV
è
½xvY
!M\88
ú¢m%
M6EF
&
ýþÿ
!OY./.ITD1.ZOZ[D$\J\%
¨C᳑
! HUWTU.WTYDU5
W.Z$KCC
”
\83! O.aU1DVDY[/GZO[/U1
ú¢
\U.5
8TGYI
EF
&
ٙ5œ–Ò
! IT.VITGWGVDU1TUOUW.Y
-.-_WGUZ
”
bYYú¢pc
;G5
-GZGU
EF
&
¤¥5œ–Ò
%
†éÌéöÒ4ú¢9
:ŒEF
&
¤¥;t¨©ŽÕ
9GY_DY
ú¢m%
CTDY/.8-UD1WUXU-
EF
&
?@¨AÐ4
!I.Z6aU16ZUHD1D
XZ[.YUHD$J`KE
¼ú¢
9UZUI.YD
EF
&
!ü—æìâ
{|Ùí|\;3¤¥


)!/U-Y.W[O[ZD5GV5
V.-UGWDH IY.WDU1 ZUSTW-TGU1 )$N<):=:
üô
%

—æ
/CB>
üô
%
!ü—æٙ‘
/CB>!IT.VIT.5
Y6ZGWDH5/CB>8DY*&&($I5/CB>8*&&(
üô
%
!ü—
æ
5G-WU1
üô
%
BVõ¼‘|5
!T.YVDYGHUVT IDY.7U5
HGVD$M>J
I›Eü!
:SF
üôú¢m%
8US1GZU1SCD-T1.Z.S6
EF
&c
Yºóú¢
@.HG_
EF
)
b!
v?
!
 ¡&[
!
pc
83;RB
EF
&
C!
7
<@&$
~#+†\ 
&QDVWDY1 OZ.W
ää
!
m%
\U.>GH
EF
)
b&!
 ¡&”Ž$°
!
—æx:žŸ ¡
b
!;>@5*?
.pcŠ—¨©k<÷à˜
@UWG/[YG
÷ø%&
) ;>@5*?
 ¡9YÛ$íÇ
é
$
øGŸá
$
ƒÇÔ ¡&6
!4mK9?9=
E* PmE\8$
n
m
ðÀ¬÷À¬vY
$
+Ô ¡
&[$ðc&
!)% n%
”>5
%m*
&
s
 ¡½
* o$

L
=
U¦5(XÙ
*
UX$
$
{m
LuvØÙPÝs&6fÈ
M\88 /N$
€
¨Â)±—˜™
! /S-N
h

”­îÀ¬
!$$ 1/.Z
-N
h

ðcŽ
)
b)!
 ¡$
N<) :=:
üô
%/CB>
üô
%I5/CB>
8*&&(
¤¥¦§
!
͓
QDVWDY1 OZ.W
=˞ۤ¥
¦§çè
)
“ ¡i¾éGÌP8
$
s
*
U
X$Yô#*
$
“
J\8

*
Ì
$
qLU±¿ ¡
ë-Y
$$
!
N
ðcë-
&
۱\J”
KCC
m

!
N$
Ô
$$ n
†ç$‡
& /U1
°¤¥ƒw
&
V¸à
¤¥;t¨©ŽÕI–
%em
Ð
m
¨%º”
$m
()º
&
sÁÕ
!*$
!
N
mǤ¥¨Â±ë
$
“Vˆ‰$±`Vˆà8Yðc¥¨Š6C™c?
‹4ÑPŒºVˆ
!V.HU[/H.HD-6ZV[ZXGWD5I.Z6G-Y6Z5
G/UHDSDZDZD-WY.IT.YDVUV$J3F?58K8&
VˆŽé
$
ítŒº
$
sŒºž¤¥V–Ù
J`KE
¼ž
$
V
¸à¤¥Ú+Øí/ã
J`KE
¼
&
“n
)m\83
?¼Ð4;犐‘ÿoÙ|
!WYUVO[XDYDH VG5
ZU1DW+DD1$C\8C
à8Y’“
T&
¨Âê
J`KE
¼
$±¿;½¬ü
!
!ü—æ
N<) :=:
üô
%
!ü—
æ
/CB>
üô
%
!ü—æ
I5/CB>8*&&(
üô
$
ü®
l $$$

&
!ü—æ
5G-WU1
üô
$l* $$$
+
¼
$
¦’
$& n
”õ,
)
“
C\8C
à8Y•
J`KE
¼
$
©
)
©
$

/U1&
±XYI›¨ü
!
Eü!
:SF
üô
$l* $$$

$
”
e T&
۩
“
C\8C
à8Y•
J`KE
¼
$
©
)
©
$

/U1&
íÇ
J`KE
¼
$
s
bYYüj]
–“
J`KE
¼ž
$
“—˜-
c
Yºó
%
™Y”Ìé
&
“
L[G1WUW6.1D&ee
š›
!\U.5>GH
ðcY¦5¨
÷
$
(ó¨ÂS
5G-WU1
Ð
/CB>
Y¦5tÑ
$
$<
צ£¤¥;t¦§Õ
)
b$!
¤¥¨÷
!
͓
8J88 )e$
¤¥š›îï
$
¥Õ.û͓ #
Hp4
¦£
$
±
9G115QTUW1D6A
=v
$Iq$e$
Ð
Iq$e$
¦£
„C¤¥žŸ
)
!

b!M\88

;>@5*?
 ¡¢£
!N<) :=:
¯
¢£I.w¤¥
$N<) :
ê
N<) :
–‘ö5Ð
U
N<) :=N<) :
<׉=Ò¢£ö5
*)+
)
(
ó†£
$
“ØÙPÝ
!$$$e$$*$# T$
LM
M\88
! /N
Ž
;>@5*?
 ¡Pô8
$N<) :
ê
N<) :
–‘ö5²Øä±
&
“
T
P
$N<) :
¤¥
¦§çès‰
!
f
&
Sm¢í¬LPÝ;<
$
T
”
* T

N<) :
¤¥¦§ç腆ƒ‘
$
$„
C¤¥žŸ
!Iq$e$)
7(ó1…
$M\88

;>@5*?
 ¡
N<) :
¤¥‰¦§
$
zû ¡bå
¢£
)
b!M\88
œ–
/CB>
k!/CB>
¾›
+œ–8Ž¢¼;/´„È¢£ô¼
$
Äůœ
–,¢£
*&+
)
®ÂÃ
M\88
¯ø+Aõ†š
/CB>
k$
ŒUt
/CB>
kV¤¥
/CB>
”
I5/CB>8*&&(
ðc,=Ë
)

†£
$
“ØÙPÝ
!$$$e$$*$# T$
LM
M\88
! /N
Ž
;>@5*?
 ¡Pô8
$ I5/CB>
-4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&
!!
Sm¢í¬LPÝ;<

Iq$e$!
f
*
Ù
)
f
!M\88

;>@5*?
 ¡
N<) :$N<) :
¤¥¦§ËÌ
S¦§ÕEUSe!<./IGYUV.1 .X-TGYG-WDYUVWU-G1H d[G1WUW6.XWTDIY.WDU1
D7IYDVVU.1V.XN<) :G1H N<) :U1H[-DH O6M\88 U1 ;>@5*?
-DZV
8*&&(
¤¥¦§çè²Ø‡
!
f
*&
“
# T
P
$
I5/CB>8*&&(
¤¥¦§çès
&
Sm¢í¬LP
Ý;<
$
“
$e
”
# T
P
$
$¤¥¦§ç蝄
C¤¥žŸ
!Iq$e$)

$
mPÝ
/CB>
¤¥¦§çèi…†ƒ‘
)
7(ó1…
$M\88
=

;>@5*?
 ¡
I5/CB>8*&&(
¤¥¦§
$
œ
–
/CB>
k)
f
*!M\88
œ–
;>@5*?
 ¡
I5/CB>8*&&(
¤¥¦§Ë
ÌS¦§ÕEUSe*!<./IGYUV.1 .X-TGYG-WDYUVWU-G1H d[G1WUW6.XWTDIY.WDU1
D7IYDVVU.1 .XI5/CB>8*&&( U1TUOUWDH O6M\88 U1 ;>@5*?
-DZV
b&!
—˜™œ–
M\88
zû
;>@5*?
 ¡¢£
!
®Âט™¯ø=éê
M\88
zû
;>@5*?
 ¡¢£
$
ŒUs—˜™
! /S-N
h

S
M\88!
/N
Æ)Ž
;>@5*?
 ¡
$
“
T
P
$

N<) :$
N<) :
¤¥¦§çè
)
(ó†£
$
—˜™S
M\88
Æ)ŽÖ½…†‡
N<) :
¤¥¦§çè
$
S
M\88
Ž±;<
$
$„C¤¥žŸ
!Iq$e$
!
f
))
7(ó1…
$
—˜™S
M\88
Æ)ŽÖ
½…†‡
;>@5*?
 ¡
N<) :
¤¥¦§çè
$
œ
– ¡¢£
)
Sl¥±;<

Iq$e$&
S
M\88
Ž±;<
*
Iq$e$!
f
&
Ù
)
f
)!
—˜™œ–
M\88
zû
;>@5*?
 ¡
N<) :$N<) :
¤¥¦§ËÌS¦§ÕEUSe)!<./IGYUV.1 .X-TGYG-WDYUVWU-G1H d[G1WUW6WTDIY.WDU1 D75
IYDVVU.1V.XN<) :G1H N<) :D7I.VDH W.M\88 U1TUOUWDH O6
YTDU1 U1 ;>@5*?-DZV
b)!
—˜™¾›
M\88
œ–
/CB>
AO›w
!
®Âט™¯ø=Aõ†š
/CB>
kéê ¡¢£
$
ŒUs—˜™
! /S-N
h

S
M\88
! /N
Æ)Ž
;>@5*?
 ¡
$
“
# T
P
$
=Ë,
I5/CB>8*&&(
”
/CB>
¤¥¦§çè
)
(ó†
£
$
—˜™S
M\88
Æ)ŽÖ½…†¯ð
I5/CB>
8*&&(
¤¥¦§çèڟ
$
S
M\88
Ž±;<
$
$„C¤¥žŸ
!Iq$e$!
f
&)
7(ó1
…
$
—˜™S
M\88
Æ)ŽÖ½…†…‰
M\88
œ–
;>@5*?
 ¡
I5/CB>8*&&(
¤¥¦§ç
è
$
¾b
/CB>
k)
b$!
—˜™Ž
;>@5*?
 ¡¢£¨©ïÝÖ

/CB>!
®Âט™¯øÜu¯’“Ô
/CB>
´éê ¡¢£
$
ŒUs—˜™
! /S-
N
h
%M\88! /N
S
/CB>
Eœ–Ò
*$+
,,,
­îÀ¬
!$$ 1/.Z-N
h

Æ)Ž
;>@5*?
 
¡
$
“
T
P
$

N<) :$N<) :
¤¥¦§çè
)
(ó†£
$
­îÀ¬
%
—˜™S
M\88
Æ)ŽÖ½
-*4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&
!!
f
&!
—˜™¯ð
M\88
œ–
;>@5*?
 ¡
I5/CB>
8*&&(
¤¥¦§ËÌS¦§ÕEUSe&!<./IGYUV.1 .X-TGYG-WDYUVWU-G1H d[G1WUW6.XWTDIY.WDU1
D7IYDVVU.1 .XI5/CB>8*&&( U1TUOUWDH O6M\88 D1TG1-DH O6
YTDU1 U1 ;>@5*?-DZV
ڟ
N<) :
¤¥¦§çè
$
S—˜™S
M\88
Æ)
Ž±;<
$
$„C¤¥žŸ
!Iq$e$ !
f
)
7(ó1…
$
­îÀ¬’®
/CB>
Ñ6Ò
$
tԗ˜™œ–
M\88
zû
;>@5*?
 ¡¢£
$
Ö½5¬ê

0&
(
’“
)
¸æ
$
Ö½®
$
—˜
™Ž
;>@5*?
 ¡¢£¨©ïÝÖ=¯
/CB>)
&!
Ã:
BCuÁ¦…
$
—˜¯ôàèwxç1TUx
P=QR
%
Q3x‘|‚,|
*+
&
t(Cè
wxyz23Ü{|
$
—˜Ö½ˆ‰$ô|
%
)*
Ճ
%
¤¥´”)-Á
**+
)
æ”
$
—˜‚È
¨
,,,
—˜™
*)+
Ö½…†ˆ‰ÿžÇ´(È
![5
1UZGWDYGZ[YDWDYGZ.OVWY[-WU.1$AAB
:æx±²$–
‘å87©
!WYG1VX.Y/U1SSY.+WT XG-W.Y$CFE5

%
!
5
èÔÕÕ{¤¥
!
!
5V/..WT /[V-ZDG-WU1$
!
5893
”
Tƒ¤¥
!XUOY.1D-WU1
¦§
$
Q3x
‘
*4+
&
—˜™‘=…†ˆ‰
CFE5


zûx:
žŸ ¡¤—” ¡”6Ž
!D7WYG-DZ[ZGY/GWYU7$
?<9

*&+
$
œ–‰³zûx:žŸ ¡
Ž – ¨ ‘
! DIUWTDZUGZ5/DVD1-T6/GZ WYG1VUWU.1$
?9C
*(+
)

$
—˜”—˜™¶¯Š‹xySz
CÙ,|
)
¬­jkt
$
h ¡îÔ

êë
(
P
$
¢£›w
slž†
$
Aõv5ô8ç-5‡-’“
$
®“
!!
Sl¥±;<

Iq$e$&
S
M\88
Ž±;<
*
Iq$e$&
S—˜™
S
M\88
Æ)Ž±;<
)
Iq$e$)
f
!
­îÀ¬ã–—˜™œ–
M\88
zû
;>@5*?
 
¡
N<) :$N<) :
¤¥¦§ËÌS¦§ÕEUSe!<./IGYUV.1 .X-TGYG-WDYUVWU-G1H d[G1WUW6.XWTDIY.WDU1
D7IYDVVU.1V.XN<) :G1H N<) :U1TUOUWDH O6YTDU1 D7I.VDH W.
M\88 YDaDYVDZ65YDS[ZGWDH O6YGIG/6-U1 U1 ;>@5*?-DZV
)
%
“¼é ¡X4=Õ´b$P=”Λ
&
Z
¯
$
õ¯ÐõÊ¢£´+·¸ ¡
$
õÙÖûq
 ¡ÕP
*+
) Á`´
*#+
$
“xy“)
=
ۀ
#—æ}~$
$
¢£ä±(LMOPä±
$
ä¨
üOP67
\-Z57N
¦§
$
=ߜ–x:žŸ 
¡¢£”OP
&;G_GSG+G
Á`´
*%+
$
“Nwx·
¸—æ}~$
$DaDY.ZU/[V!/CB>
œ–Ò

+ä±
¢£”±|x:·¸
&8[ [^_U
Á`´
*(+
$
¢£
œ–ÒÖ½œ–
M
*
B
*
zûx:žŸ ¡ÕP
)
¶”(ó¶1…
$
“ËÌë›t
$
¢£+±|x:
žŸ ¡·¸
$
œ–¢£ÅÖ=ˆ‰$·¸
)
N<)
¯óT¢£¤¥
$
 ¡vŽ„8
N<)
!N<) :
Aõ()<‘Ù<ÑБP
$
Tƒ¬
N<)
56ÿb
$
–‘®
N<) :$
$–f¯Ê
$
Äů
N<) :
¤¥¦§ç艝=½¢£båö
5
*4+
)
ŒUàá(ó¦…
$M\88
’® ¡êë
zûÒ
$
LM’“Pô8
$
=¯ð
N<) :
ê
N<) :
–‘
$
ä¨
N<) :
¤¥¦§çè
$

;>@5
*?
 ¡¢£bå
$
´—˜™Ö½‡
N<) :
¤¥
¦§çè
$
œ–
M\88
zû ¡¢£
)
àᦅ
$
“å¾ë›t
$/CB>
k-)4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&
O¯†š ¡¢£3Vk<å
**$+
$/CB>
k<
AO›wä¨Ö½¯°ó³ôS8Ž¢Ü„
$
œ–
8Ž¢¼;/´„È¢£ô¼
$

$
†š
/CB>
k*&+
)
ŒUb
È
$
LM
M\88
’“Pô8
$M\88
Ö½…†‡

;>@5*?
 ¡
I5/CB>
¤¥¦§çè
$/CB>
k
$
´—˜™=ڟœ–
/CB>
k&
æ”
$
ŒU‘bÈ
$
­îÀ¬
$
’®‰5˄
/CB>
œ–Ò
**5*&+
$
Ö½0&—˜
™t ¡¢£œ–’“
)
¸æ
$
ŒU®
$
—˜™
Ö=¯Aõ†š
/CB>
kM\88
zû ¡¢£
&
—˜™Ž
;>@5*?
 ¡¢£
¨©ïÝÖ=¯
/CB>)
ïæ
$
ŒU‘ýC6
ƒŒ¸1…—˜™“ô”tx:žŸ ¡¢£
Æǒ“
)
Až/Û
$M\88
œ–
/CB>
kzûx:žŸ ¡b墣
&
—˜™†š
/CB>
k§
$
¶Ö=ů$Ž ¡¢£’“”¨©•–
)

„…†‡
#
* +!FYDD1 K>$NDaU1D\eC.OD.Y1.WW.ODB M.+VDZD-WUaDG[W.IT5
GS6G1H -DZHDGWT S.aDY1 -DZXGWD*]+e* * +!9GZU-HG1 9<$;.S[-TU8$;UVTU1.:e3[W.ITGS6U1 G/.[VD/.H5
DZ.XHUVWGZ/6.IGWT6+UWT YU//DH aG-[.ZDV.YTDYDHUWGY6U1-Z[VU.1
O.H6/6.IGWT6*]+e3[W.ITGS6$*$$%$)!&#)4#e
* ) +!FZU-_ K$ \GYWT 8$ 9G-ZD.H @Ee3[W.ITGS6#-DZ[ZGYG1H /.ZD-5
[ZGY/D-TG1UV/V*]+e]JGWT.Z$*$$$**!#)e
* & +!@ZU.1V_6K]$9DU0DY3]$<.H.S1.Je3[W.ITGS6G1H I%$8# _U5
1GVD*]+e3[W.ITGS6$*$$$!#4e
* +!JDYU6GVG/65CTG1HGaG1 8$]UG1S9$8-T.D1ZDU1 J$ DWGZe3[W.IT5
GS6# /.ZD-[ZGY/G-TU1DY6$ YDS[ZGWU.1$ G1H U/IZU-GWU.1VX.YYD1GZ
IGWT.IT6VU.Z.S6*]+e3/]JT6VU.Z>D1GZJT6VU.Z$*$$4$*4%
!*#E*&&e
* # +!8GZ/U1D1 3$@GGY1UYG1WG@$@G[IIU1D1 3e\D-ZU1 U1WDYG-W./D
-.1WY.ZVWTD-Y.VVWGZ_ ODW+DD1 GI.IW.VUV$G[W.ITGS6G1H U1XZG//G5
V./DG-WUaGWU.1#U/IG-W.1 WTDGSU1SIY.-DVV*]+e3SDU1S>DV
>Da$*$)$*!*#*$e
* % +!
ñò
$
óô
$
üýþ
$
Á
e
—˜„©…†š
];@=\-Z5*
kO´ˆ‰´™wxzx:
=
Ž·¸•–
*]+e
$\$
B,-.
$*$)$*(!#)e
* ( +!JD1SN$RG1S]$;U1S<$DWGZe>TDU1 U1TUOUWVU1WDSYU15ZU1_DH _U5
1GVDD7IYDVVU.1 G1H YDS[ZGWDV/GWYU7/DWGZ.IY.WDU1GVD54=WUVV[D
U1TUOUW.Y.X/DWGZ.IY.WDU1GVD5 YGWU.U1 TUST SZ[-.VD5U1H[-DH DIU5
WTDZUGZ5/DVD1-T6/GZWYG1VUWU.1 .XYD1GZW[O[ZGY-DZ*]+e\U.Z
JTGY/\[Z$*$*$)!$##%#e
* 4 +!MDK$NDDN$RG1S]$DWGZeJYDaD1WUaDDXD-WVG1H /D-TG1UV/V.X
YTDU1 .1 YD1GZU1WDYVWUWUGZXUOY.VUVU1 .OVWY[-WUaD1DITY.IGWT6*]+e
\U.ZJTGY/\[Z$*$$)&!(# *4e
*$+!FDUVVZDY?@$8-TZUWM]eCTDI.WD1WUGZOD1DXUWV.XYGIG/6-U1 .1
YD1GZX[1-WU.1$W.ZDYG1-D$XUOY.VUV$G1H /GZUS1G1-6X.Z.+U1SWYG1V5
IZG1WGWU.1 *]+e@UH1D6:1W$ *$$$%(!#$%e
*+!QG1SM$8.1SM$R[D]$DWGZe>TD[/.XU-U1GZD!GWYGHUWU.1GZ
WGOGVD86VW>Da$*$*$!%#**+!MG1 Z^U-D_ 38$>..X<]$8G1HDYV.1 9Q$DWGZeCTDDXD-W.X
TD[/BXU-U1GZD$+UWT G1H +UWT.[W\D1G^DIYUZ
.1 WTDIY.SYDVVU.1 .X1GW[YGZ6.--[YU1S-TY.1U-_UH1D6HUVDGVDU1
-GWV*]+e]` DW:1WDY1 9DH$*$&$*(!&#**e
*)+!@.6G/G]$9.YUWG:$@.OG6GVTU;e8U/[ZWG1D.[VHDWDY/U1GWU.1 .X
G1WTYGd[U1.1DVU1 YT[OGYO O6TUST5IDYX.Y/G1-DZUd[UH -TY./GW.S5
YGIT6G1H -GIUZGY6DZD-WY.IT.YDVUV*]+e]&!=*#()e
*&+!F[.cM$NU[ bM$KGU<8$DWGZe>TDU1 U1TUOUWVYD1GZW[O[ZGY
DIUWTDZUGZ-DZT6IDYWY.IT6G1H D7WYG-DZ[ZGY/GWYU7G--[/[ZGWU.1
U1H[-DH O6WYG1VX.Y/U1SSY.+WT XG-W.YODWG *]+e3-WGJTGY/G-.Z
8U1$*$$$**!$#4)&e
*+!@Y.D/DYF$NDaU1D\e3[W.ITGSU--DZHDGWT#WTDVW.Y6.XG/UV5
1./DY*]+e;GW>Da9.Z*#+!YDH[-DVUV-TD/UG=YDIDYX[VU.1 U1H[-DH IY.7U/GZG1H HUVWGZW[O[ZGY
GI.IW.VUVG1H G[W.ITGS6*]+eCYG1VIZG1WGWU.1$*$$%$(& !4#
()e
*%+!;G_GSG+G8$;UVTUTGYG@$:1[U@$DWGZe:1a.ZaD/D1W.XG[W.ITGS6
U1 WTDITGY/G-.Z.SU-GZDXD-WV.XWTD/CB>U1TUOUW.YDaDY.ZU/[V
U1 G-[WD_UH1D6U10[Y6*]+e?[Y]JTGY/G-.Z$*$*$#4#!=)#
&)e
*(+!8[ [^_U<$:VG_GR$CG_GOGWG_DR$DWGZeJGYWU-UIGWU.1 .XG[W.IT5
GS6U1 YD1GZUV-TD/UG=YDIDYX[VU.1 U10[Y6*]+e\U.-TD/\U.IT6V
>DV<.//[1$*$$($)#(!# $$e
*4+!@GOD6GR$9U^[VTU/G;$AD1.C$DWGZeN<)$G/G//GZUG1 T./.5
Z.S[D.X6DGVW3IS(I$UVZ.-GZU^DH U1 G[W.ITGS.V./D/D/OYG1DV
GXWDYIY.-DVVU1S*]+e?9\B$*$$$$4!*#%*$e
**$+!][1S.8 M$YDS[ZGWU.1 .XG[W.ITGS6
*]+eE?\8 NDW$*$$$(&!%#*(%e
**+!8DTSGZ8 ;e>GIG/[1D!>3J3$YGIG/6-U1$VUY.ZU/[V#/D-TG5
1UV/.XG-WU.1 U//[1.V[IIYDVVUaDDXD-WYDV[ZWVXY./OZ.-_GHD.X
VUS1GZWYG1VH[-WU.1 G1H U1TUOUWU.1 .X-DZ-6-ZDIY.SYDVVU.1 *]+e
***+!8DTSGZ8 ;e8UY.ZU/[V#UWVHUV-.aDY6$ OU.Z.SU-GZIY.IDYWUDV$ G1H
/D-TG1UV/.XG-WU.1 *]+eCYG1VIZG1WJY.-$*$$)$)!) 8[IIZ#
%8e
**)+!MG6;$8.1D1ODYS;eAIVWYDG/G1H H.+1VWYDG/.X/CB>*]+e
FD1DVKDa$ *$$&$(!##4*#e
**&+!EU1SGYK<$\ZD1UV]eCGYSDW.XYGIG/6-U1!CB>#G1 U1WDSYGW.Y.X
1[WYUD1WG1H SY.+WT XG-W.YVUS1GZVG1H -..YHU1GW.Y.X-DZSY.+WT
G1H -DZ-6-ZDIY.SYDVVU.1 *]+eB1-.SD1D$*$$&$*)!(#)e
-&4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&
<@/?RG/-E,?RC-A.I,@LEC?.A@A.AC.K.B.AS -GB@MC-S.RME@B?.A
?OME?II.@A.AE?A-/BGKG/-E?M.BC?/.-/R?/IJ.- E?SG/-B.AS ,=68
I.SA-/.AS M-BCT-D -RB.J-B.@A
CAR[D

$ 8A;QDU
$*
!
$ FANU[5OG.
)
$ Q3;RU5SG1S
$&
$ MAMG.

$ N:AM.1S

!e@)4)7%39 A4$!$,$)&0B!1)*6!4)74)$ ;7*eF!7+4, I%&#!3!7/=&4(!$7/&089!)4):)1!3!)$ 9)>0!/!7$)1 =&4(!$7/&0;7;7)e6)(7%$-)$&0:&/)3,/7%2!+7/!+$ ?!#)%4!$*&0G7-7749!$ G7-7749!&$4E)(4($ F7(7&
&e6)(7%$-)$&089!)4):)1!3!)$ ;70!/!7$)1 =&4(!$7/&0;7;7*4KIBE-RB+!6KY?RB.J?# C.D7IZ.YDWTDDXD-WVG1H /.ZD-[ZGY/D-TG1UV/V.XYTDU1 .1 YDH[-U1SVWGYaGWU.15U1H[-DH G[W.ITGSU-
IY.WDU1 D7IYDVVU.1 U1 YD1GZW[O[ZGYDIUWTDZUGZ!;>@5*?-DZVe;>@5*?-DZVW.ODU1 WTDVWGWD.XVWGYaGWU.1e3XWDYWTDU1WDYaD1WU.1 .XM\88 X.Y$$$e$$* G1H # T.[YV$XUYVWZ6$WTDIY.WDU1 D7IYDVVU.1
.X/U-Y.W[O[ZD5GVV.-UGWDH IY.WDU1 ZUSTW-TGU1 )!N<) :=:$+TU-T UVG_D6IY.WDU1 U1 G[W.ITGS6$+GVHDWD-WDHe8D-.1HZ6$WTDIY.WDU1
D7IYDVVU.1V.X/G//GZUG1 WGYSDW.XYGIG/6-U1!/CB>G1H IT.VIT.Y6ZGWDH5/CB>8DY*&&(!I5/CB>8*&&(+DYDD7G/U1DHe31H WTD1$
GXWDYWTD-.5WYDGW/D1W.XYTDU1! /S-N
h
G1H M\88! /N+UWT.[W.Y+UWT /CB>U1TUOUW.Y$YGIG/6-U1!$$ 1/.Z-N
h
$WTDIY.WDU1
D7IYDVVU.1V.XN<) :=:$/CB>G1H I5/CB>8*&&( +DYDWDVWDH$YDVID-WUaDZ6e8?IG/B# M\88 -.[ZH U1H[-DWTD[I5YDS[ZGWU.1 .XN<) :
G1H WTDH.+15YDS[ZGWU.1 .XI5/CB>8*&&( GWIY.WDU1 D7IYDVVU.1 ZDaDZU1 ;>@5*?-DZVeCTD-.5WYDGW/D1W.XYTDU1 G1H M\88 -.[ZH YD5
aDYVDZ6YDS[ZGWDWTDIY.WDU1 D7IYDVVU.1V.XN<) :G1H I5/CB>8*&&( U1 ;>@5*?-DZVVUS1UXU-G1WZ6eCTD-.5WYDGW/D1W.XYGIG/6-U1$
YTDU1 G1H M\88 -.[ZH YD-.aDYWTDZDaDZ.XN<) :IY.WDU1 D7IYDVVU.1 U1 M\885U1WDYaD1DH ;>@5*?-DZVe0@AR/GI.@A# M\88 U1H[-DV
G[W.ITGS6U1 YD1GZW[O[ZGYDIUWTDZUGZ-DZVO6U1TUOUWU1S/CB>VUS1GZU1SIGWT+G6G-WUaGWU.1e>TDU1 YDH[-DVWTDG[W.ITGSU-IY.WDU1 D75
IYDVVU.1 U1 YD1GZW[O[ZGYDIUWTDZUGZ-DZVWTY.[ST YDS[ZGWU1S/CB>VUS1GZU1SIGWT+G6G-WUaGWU.1$+TU-T UVWTDI.VVUOZDDXD-WVG1H /.ZD-[5
ZGY/D-TG1UV/Ve
*W?D T@EFI+!YTDU1& G[W.ITGS6& /CB>VUS1GZU1SIGWT+G6& YD1GZW[O[ZGYDIUWTDZUGZ-DZV& YGIG/6-U1
F@.#(a)`ZPRYR,,()(&

ˆ‰-0
!
Š‹‹
#
-4$&-

)4
‚
*
r
*$&
n

o
!!!!!! ! ! ! ! ! !!!! ! ! ! !
.`Ze)4$:VV[D!*
;.aD/ODY$ *$&