<ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><th id="pb13h"><ins id="pb13h"></ins></th></ins>
<cite id="pb13h"><th id="pb13h"></th></cite>
<del id="pb13h"></del>
<cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"><noframes id="pb13h"><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<del id="pb13h"></del><menuitem id="pb13h"><span id="pb13h"><menuitem id="pb13h"></menuitem></span></menuitem>
<del id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins><var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"></ins><del id="pb13h"><noframes id="pb13h"><var id="pb13h"><span id="pb13h"><menuitem id="pb13h"></menuitem></span></var><var id="pb13h"><noframes id="pb13h">
<del id="pb13h"><th id="pb13h"></th></del>
<menuitem id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"><span id="pb13h"></span></var><var id="pb13h"></var><var id="pb13h"></var>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins><cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h">
<var id="pb13h"></var>
<var id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"><span id="pb13h"></span></var><ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite> <del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"><span id="pb13h"></span></del>
<ins id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"><th id="pb13h"><ins id="pb13h"></ins></th></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></cite><del id="pb13h"><span id="pb13h"></span></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"><noframes id="pb13h">
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<ins id="pb13h"></ins>
<ins id="pb13h"><span id="pb13h"></span></ins>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite> <del id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"></ins><var id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<var id="pb13h"></var>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></var>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<del id="pb13h"></del><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><video id="pb13h"><var id="pb13h"></var></video></cite><cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var><del id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<cite id="pb13h"></cite><var id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></var>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"></cite>
<del id="pb13h"></del><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"><span id="pb13h"></span></var><cite id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"></var>
<var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"></ins>
<cite id="pb13h"></cite>
<var id="pb13h"><span id="pb13h"></span></var><var id="pb13h"><noframes id="pb13h">
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"></del>
<var id="pb13h"></var>
<cite id="pb13h"></cite>
<del id="pb13h"><span id="pb13h"></span></del>
<del id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<var id="pb13h"></var>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h"><del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><var id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><cite id="pb13h"></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><video id="pb13h"><var id="pb13h"></var></video></cite>
<del id="pb13h"></del>
<del id="pb13h"></del><cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var><ins id="pb13h"><span id="pb13h"></span></ins><cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins><del id="pb13h"></del>
<ins id="pb13h"></ins>
<ins id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></ins>
<var id="pb13h"></var>
<del id="pb13h"></del><ins id="pb13h"><noframes id="pb13h"> <cite id="pb13h"></cite>
<var id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><span id="pb13h"></span></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></ins>
<del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"></cite>
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h">
<thead id="pb13h"><video id="pb13h"><thead id="pb13h"></thead></video></thead>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"></ins><var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del><ins id="pb13h"></ins>
<cite id="pb13h"><th id="pb13h"></th></cite><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><th id="pb13h"></th></cite>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><del id="pb13h"><noframes id="pb13h">
<del id="pb13h"><span id="pb13h"></span></del>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins><cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"></del>
<ins id="pb13h"></ins><cite id="pb13h"><th id="pb13h"></th></cite>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<var id="pb13h"><span id="pb13h"></span></var>
<del id="pb13h"></del><var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><ins id="pb13h"></ins>
<address id="pb13h"></address>
<var id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></var>
<ins id="pb13h"><th id="pb13h"><ins id="pb13h"></ins></th></ins>
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"></ins><cite id="pb13h"></cite>
<del id="pb13h"></del>
<cite id="pb13h"><span id="pb13h"></span></cite><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><th id="pb13h"></th></cite>
<cite id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"><span id="pb13h"><thead id="pb13h"></thead></span></menuitem>
<var id="pb13h"></var><ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><del id="pb13h"></del>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"></del>
<var id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"></span></var>
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var><cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></ins>
<ins id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"></cite><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del> <ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"><video id="pb13h"><var id="pb13h"></var></video></cite>
<del id="pb13h"></del>
<del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><span id="pb13h"></span></cite>
<var id="pb13h"></var>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"><span id="pb13h"></span></del><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"> <progress id="pb13h"></progress><ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><cite id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><var id="pb13h"><span id="pb13h"></span></var><var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<cite id="pb13h"><span id="pb13h"></span></cite><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del><ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<var id="pb13h"></var>
<cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<cite id="pb13h"><span id="pb13h"></span></cite>
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"><th id="pb13h"><ins id="pb13h"></ins></th></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><cite id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></cite>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><menuitem id="pb13h"><span id="pb13h"><thead id="pb13h"></thead></span></menuitem>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<var id="pb13h"></var><del id="pb13h"></del>
<ins id="pb13h"></ins> <listing id="pb13h"></listing>
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><var id="pb13h"><span id="pb13h"></span></var>
<cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite><menuitem id="pb13h"><span id="pb13h"><menuitem id="pb13h"></menuitem></span></menuitem>
<cite id="pb13h"></cite>
<menuitem id="pb13h"><span id="pb13h"><menuitem id="pb13h"></menuitem></span></menuitem>
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"></cite>
<ins id="pb13h"></ins><del id="pb13h"></del><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"></var><cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite>
<ins id="pb13h"></ins><ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h">
<del id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"><noframes id="pb13h"><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><cite id="pb13h"><th id="pb13h"></th></cite>
<del id="pb13h"></del><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins> <strike id="pb13h"><cite id="pb13h"><dl id="pb13h"></dl></cite></strike><ins id="pb13h"></ins>
<ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><th id="pb13h"></th></ins>
<del id="pb13h"></del>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></var>
<del id="pb13h"></del>
<var id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<cite id="pb13h"></cite> <del id="pb13h"></del><del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><span id="pb13h"></span></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><del id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"></span></cite>
<cite id="pb13h"><span id="pb13h"></span></cite>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del><ins id="pb13h"></ins>
<var id="pb13h"><noframes id="pb13h">
<var id="pb13h"><span id="pb13h"></span></var>
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite>
<del id="pb13h"></del><del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<var id="pb13h"><span id="pb13h"></span></var>
<menuitem id="pb13h"></menuitem>
<cite id="pb13h"><span id="pb13h"></span></cite>
<var id="pb13h"><span id="pb13h"></span></var>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<menuitem id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<del id="pb13h"></del> <ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<cite id="pb13h"></cite>
<menuitem id="pb13h"></menuitem>
<i id="pb13h"><noframes id="pb13h">
<cite id="pb13h"></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"></span></var><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><ins id="pb13h"></ins>
<del id="pb13h"></del>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"></del><cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<del id="pb13h"></del>
<var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<var id="pb13h"></var>
<del id="pb13h"></del><var id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<del id="pb13h"></del><ins id="pb13h"></ins>
<var id="pb13h"><span id="pb13h"></span></var>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><span id="pb13h"></span></cite>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></cite>
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"><th id="pb13h"></th></ins><var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"></menuitem>
<cite id="pb13h"><noframes id="pb13h">
<var id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></var>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<thead id="pb13h"></thead>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"><span id="pb13h"></span></cite><ins id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></ins><cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"></span></cite>
<var id="pb13h"><noframes id="pb13h"><menuitem id="pb13h"><span id="pb13h"><menuitem id="pb13h"></menuitem></span></menuitem>
<del id="pb13h"></del>
<del id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<del id="pb13h"><span id="pb13h"></span></del>
<ins id="pb13h"></ins><var id="pb13h"><noframes id="pb13h">
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var><cite id="pb13h"><span id="pb13h"><var id="pb13h"></var></span></cite>
<var id="pb13h"></var><ins id="pb13h"><span id="pb13h"></span></ins>
<cite id="pb13h"></cite>
<cite id="pb13h"><span id="pb13h"></span></cite>
<span id="pb13h"><del id="pb13h"><span id="pb13h"></span></del></span>
<del id="pb13h"></del>
<cite id="pb13h"><th id="pb13h"></th></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><ins id="pb13h"></ins>
<cite id="pb13h"><span id="pb13h"></span></cite>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"></del>
<var id="pb13h"></var><cite id="pb13h"><span id="pb13h"><cite id="pb13h"></cite></span></cite>
<cite id="pb13h"></cite>
<cite id="pb13h"></cite>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<del id="pb13h"></del><cite id="pb13h"><th id="pb13h"></th></cite>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<del id="pb13h"><span id="pb13h"></span></del>
<del id="pb13h"></del>
<cite id="pb13h"><span id="pb13h"></span></cite>
<var id="pb13h"><noframes id="pb13h">
<del id="pb13h"></del>
<ins id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><del id="pb13h"></del><var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<var id="pb13h"><noframes id="pb13h"><var id="pb13h"></var>
<ins id="pb13h"></ins>
<var id="pb13h"></var>
<cite id="pb13h"></cite><ins id="pb13h"><noframes id="pb13h"><del id="pb13h"></del>
<ins id="pb13h"><span id="pb13h"><ins id="pb13h"></ins></span></ins>
<cite id="pb13h"><th id="pb13h"><cite id="pb13h"></cite></th></cite><del id="pb13h"><th id="pb13h"><del id="pb13h"></del></th></del>
<listing id="pb13h"><var id="pb13h"></var></listing><cite id="pb13h"></cite>
<ins id="pb13h"></ins>
<cite id="pb13h"></cite>
<cite id="pb13h"><noframes id="pb13h"><cite id="pb13h"><th id="pb13h"></th></cite>
<strike id="pb13h"><cite id="pb13h"><strike id="pb13h"></strike></cite></strike>
<del id="pb13h"></del>
<ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h">
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins><cite id="pb13h"><noframes id="pb13h"><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<cite id="pb13h"><noframes id="pb13h"> <ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite><ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<del id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><noframes id="pb13h">
<cite id="pb13h"><th id="pb13h"><ins id="pb13h"></ins></th></cite>
<ins id="pb13h"></ins><ins id="pb13h"></ins>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><cite id="pb13h"></cite>
<cite id="pb13h"></cite>
<thead id="pb13h"></thead>
<listing id="pb13h"><cite id="pb13h"></cite></listing><var id="pb13h"></var><thead id="pb13h"></thead>
<ins id="pb13h"></ins>
<ins id="pb13h"><noframes id="pb13h"><ins id="pb13h"></ins>
Agilent

要聞時事名企會展招標中標食品檢測生物醫藥能源環境

吃飽了才有力氣減肥 研究發現IL-27可促進脂肪細胞“燃燒”

2021年11月26日 16:24:41來源:儀器網

分享:
人氣:2132
  【儀器網 生物醫藥】打工人長胖真的好容易,一邊說著“減肥”,一邊又說著“不吃飽哪有力氣減肥”,脂肪細胞好不留情的堆積,IMB指數從正常到偏重再到超重,難道人體內就沒有一個細胞、哪怕是一個細胞因子能懂點事,去管管脂肪細胞嗎?
 
  其實,真的有。11月24日,暨南大學醫學部生物醫學轉化研究院的尹芝南教授團隊在Nature雜志在線發表了題為《白細胞介素27信號促進脂肪細胞產熱和能量消耗》的論文,論文中首次發現了IL-27能夠直接靶向促進脂肪細胞棕色化和產熱,并以此來減輕肥胖和改善Ⅱ型糖尿病。
 
  研究發現IL-27可促進脂肪細胞分化并產生熱量
 
  人體內的脂肪細胞大體可分為白色脂肪細胞和棕色脂肪細胞,這兩類細胞在形態、功能等方面有很大差異。白色細胞從形態上來看是但單泡脂肪細胞,它有90%的成分是脂滴,主要功能就是儲存脂質,體積最多能夠增加1000倍,是肥胖的原因所在;而褐色脂肪細胞形態上是多泡脂肪細胞,簡言之就是細胞內的脂滴很小,它的主要功能是產生熱量。
 
  因此,當IL-27促進白色細胞向棕色細胞轉化時,脂質被消耗,體積減小,產生的熱量增多,人自然也就瘦了。
 
  研究進行之前,研究人員通過臨床觀察發現當肥胖病人完成減肥手術后他們的IL-27的含量由偏低轉為正常,由此發現潛在靶點;研究采用利用構建高脂飲食誘導小鼠肥胖的模型,并結合之前肥胖病人的樣本,發現IL-27可以激活脂肪細胞產熱蛋白(UCP1)表達,介導分化和產熱。
 
  IL-27有著良好的成藥潛力 除減重外還可以改善Ⅱ型糖尿病
 
  不僅如此,研究人員還發現了IL-27的成藥性。在動物實驗中,實驗人員通過為小鼠注射重組IL-27,減輕了小鼠體重,并在此過程中發現胰島素的信號敏感性也被改善。胰島素信號響應問題一直是Ⅱ型糖尿病無法翻越的“大山”,但通過IL-27的協調,降糖過程變得簡單順利;更為重要的是,IL-27作為體內正常表達分子,安全性高于人工合成的外源化合物,在藥物治療適應癥和安全性上都表現出良好的成藥潛力。
 
  如果此項研究成果轉化成功,那么將有望從機制上改善胰島素的信號敏感性,可以使人在不節食、不做其他運動輔助的情況下安全減肥減輕體重、改善Ⅱ型糖尿病。
 
  但藥物的研發并不是一蹴而就的,從基礎研究到藥物發現、從藥物發現到進入開發期、再到后期的注冊審評和生產上市,最少還要5年,研究人員在11月25日暨南大學的發布會上強調。
 
  發布會上研究人員還透露了接下來的研究方向,未來團隊將繼續研究IL-27,從IL-27的變化中預判身體的健康狀況。
 
  (資料來源:中國新聞網、暨南大學、科技日報)
(本文來源:儀器網,轉載請注明出處
儀器網官方微信
@儀器網
已推薦
0

全年征稿 / 資訊合作

聯系郵箱:970297226@qq.com

我要評論

文明上網,理性發言。(您還可以輸入200個字符)

所有評論僅代表網友意見,與本站立場無關。

  • 凡本網注明“來源:儀器網”的所有作品,均為浙江興旺寶明通網絡有限公司-儀器網合法擁有版權或有權使用的作品,未經本網授權不得轉載、摘編或利用其它方式使用上述作品。已經本網授權使用作品的,應在授權范圍內使用,并注明“來源:儀器網”。違反上述聲明者,本網將追究其相關法律責任。
  • 本網轉載并注明來自其它來源(非儀器網)的作品,目的在于傳遞更多信息,并不代表本網贊同其觀點或和對其真實性負責,不承擔此類作品侵權行為的直接責任及連帶責任。其他媒體、網站或個人從本網轉載時,必須保留本網注明的作品第一來源,并自負版權等法律責任。
  • 如涉及作品內容、版權等問題,請在作品發表之日起一周內與本網聯系,否則視為放棄相關權利。
MTS工業系統(中國)有限公司

第7屆廣州國際生物技術大會暨展覽會
第7屆廣州國際生物技術大會暨展覽會

時間:2022.09.15~2022.09.17 地點:廣州·廣交會展館C區


返回首頁官方微信
回到頂部
我好像找到你的敏感点了宝宝,少妇户外找男人野战视频,高清在线一区二区在线,97se综合亚洲影院 <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <文本链> <文本链> <文本链> <文本链> <文本链> <文本链>