in-vitro-differentiation-naive-cd4-t-cells-into-pathogenic-th17-cells

In Vitro Differentiation of Naive CD4<sup>+</sup> T Cells into Pathogenic Th17 Cells in Mouse

In vitro T cell differentiation techniques are essential for both functional and mechanistic investigations of CD4+ T cells. Pathogenic Th17 cells have ...

Zhongda Hospital Affiliated to Southeast University

Southeast University

A &#x81EA;&#x7EC4;&#x88C5;&#x6DF7;&#x5408;&#x5BF9;&#x77F3;&#x58A8;&#x70EF;&#x7EB3;&#x7C73;&#x91D1;&#x4FEE;&#x9970;&#x7535;&#x6781;&#x4E3A;&#x4F4E;&#x6F5C;&#x529B; NADH &#x68C0;&#x6D4B;&#x53D6;&#x5F97;&#x4E86;&#x3002;&#x6211;&#x4EEC;&#x7528;&#x5929;&#x7136;&#x9AD8;&#x5206;&#x5B50;&#x58F3;&#x805A;&#x7CD6; (&#x6377;) &#x6765;&#x534F;&#x52A9;&#x6C34;&#x6EB6;&#x6DB2;&#xFF0C;&#x77F3;&#x58A8;&#x70EF;&#x7684;&#x7A33;&#x5B9A;&#x548C;&#x56FA;&#x5B9A;&#x8D1F;&#x7535;&#x91D1;&#x7EB3;&#x7C73;&#x7C92;&#x5B50; (NPs) &#x901A;&#x8FC7;&#x9759;&#x7535;&#x5438;&#x5F15;&#x529B;&#x3002;Au NPs &#x534F;&#x540C; NADH &#x7684;&#x50AC;&#x5316;&#x6C27;&#x5316;&#x77F3;&#x58A8;&#x70EF;&#x5C11;&#x6BD4;&#x6B63;&#x9762; mV overpotential ca.220 &#x88F8;&#x7535;&#x6781;&#xFF0C;&#x5E76;&#x663E;&#x8457;&#x589E;&#x52A0;&#x5F53;&#x524D;&#x6C27;&#x5316;&#x3002;&#x57FA;&#x4E8E;&#x8FD9;&#x6837;&#x7684;&#x5B89;&#x57F9;&#x4F20;&#x611F;&#x5668;&#x4FEE;&#x9970;&#x7535;&#x6781;&#x68C0;&#x6D4B; NADH &#x5C55;&#x793A;&#x826F;&#x597D;&#x7684;&#x7EBF;&#x6027;&#xFF0C;&#x4ECE; 1.5 &#x5230; 320 &mu; M&#xFF0C;&#x5E76;&#x663E;&#x793A;&#x4E0E;&#x4F4E;&#x68C0;&#x6D4B;&#x9650;&#x7684; 1.2 &mu; M &#x7684;&#x9AD8;&#x7075;&#x654F;&#x5EA6; (S/N = 3)&#x3002;&#x5B83;&#x8FD8;&#x53EF;&#x4EE5;&#x6392;&#x9664;&#x5E38;&#x89C1;&#x5E72;&#x6270;&#x7535;&#x6D3B;&#x6027;&#x5316;&#x5408;&#x7269;&#x5982;&#x6297;&#x574F;&#x8840;&#x9178;&#x548C;&#x62E5;&#x6709;&#x826F;&#x597D;&#x7684;&#x53EF;&#x91CD;&#x590D;&#x6027;&#x548C;&#x4E1A;&#x52A1;&#x7A33;&#x5B9A;&#x3002;&#x8FD9;&#x79CD;&#x6770;&#x51FA;&#x6027;&#x80FD;&#x7684;&#x77F3;&#x58A8;&#x70EF;&#x80FD;&#x591F;&#x5927;&#x5927;&#x63D0;&#x9AD8;&#x9176;&#x4E0E;&#x7535;&#x6781;&#x4E4B;&#x95F4;&#x7684;&#x7535;&#x5B50;&#x8F6C;&#x79FB;&#x4E0E;&#x975E;&#x76DF; RGO/&#x6377;&#x7535;&#x5F71;&#x5EFA;&#x8BAE;&#x6784;&#x5EFA;&#x57FA;&#x4E8E;&#x65B0;&#x578B;&#x77F3;&#x58A8;&#x70EF;&#x8131;&#x6C22;&#x9176;&#x751F;&#x7269;&#x4F20;&#x611F;&#x5668;&#x7684;&#x8BFA;&#x8A00;&#x3002;

&#x50AC;&#x5316;&#x6C27;&#x5316;&#x548C; &beta;-NADH &#x81EA;&#x7EC4;&#x88C5;&#x4F7F;&#x7528;&#x6DF7;&#x5408;&#x578B;&#x7684;&#x91D1;&#x7EB3;&#x7C73;&#x7C92;&#x5B50;&#x548C;&#x77F3;&#x58A8;&#x70EF;&#x7684;&#x6D4B;&#x5B9A;&#x3002;

A self-assembly hybrid of gold nanoparticles on graphene modified electrodes for low-potential NADH detection has been achieved. We used the natural polymer chitosan (Chit) to assist the stabilization of graphene in aqueous solution, and immobilize the electronegative Au nanoparticles (NPs) through electrostatic attraction. The synergy of Au NPs with graphene for catalytic oxidation of NADH made the overpotential ca. 220 mV less positive than that on the bare electrode, and remarkably increased the oxidation current. The amperometric sensors based on such modified electrodes for detection of NADH exhibited a good linearity from 1.5 to 320 Î¼M, and showed high sensitivity with a low detection limit of 1.2 Î¼M (S/N = 3). It could also exclude common interfering electroactive compounds like ascorbic acid and possessed good reproducibility and operational stability. Such eminent performance of the Au-RGO/Chit film together with the ability of graphene to significantly enhance the electron transfer between enzymes and the electrode suggested its promise for constructing novel graphene based dehydrogenase biosensors.

Catalytic oxidation and determination of Î²-NADH using self-assembly hybrid of gold nanoparticles and graphene.

A auto-assemblage hybride de nanoparticules d&#39;or sur le graph&egrave;ne modifi&eacute;s &eacute;lectrodes pour d&eacute;tection de NADH faible potentiel a &eacute;t&eacute; r&eacute;alis&eacute;e. Nous avons utilis&eacute; le chitosan polym&egrave;re naturel (Chit) pour aider la stabilisation du graph&egrave;ne en solution aqueuse et immobiliser les nanoparticules d&#39;UA &eacute;lectron&eacute;gatifs (NPs) par attraction &eacute;lectrostatique. La synergie des Au NPs avec le graph&egrave;ne pour l&#39;oxydation catalytique du NADH fait la surtension environ 220 mV moins positive que celle sur l&#39;&eacute;lectrode nue et remarquablement augment&eacute; le courant d&#39;oxydation. Les capteurs amp&eacute;rom&eacute;triques bas&eacute;es sur une telle modification &eacute;lectrodes pour la d&eacute;tection du NADH pr&eacute;sentait une bonne lin&eacute;arit&eacute; de 1,5 &agrave; 320 &mu;M et ont montr&eacute; une sensibilit&eacute; &eacute;lev&eacute;e avec une limite de d&eacute;tection faible de 1,2 &mu;M (S/N = 3). Il pourrait &eacute;galement exclure des compos&eacute;s de polym&egrave;res &eacute;lectroactifs interf&eacute;rentes courants tels que l&#39;acide ascorbique et poss&eacute;d&eacute;e bonne reproductibilit&eacute; et stabilit&eacute; op&eacute;rationnelle. Ce &eacute;minent performance du film ainsi que la capacit&eacute; du graph&egrave;ne &agrave; am&eacute;liorer consid&eacute;rablement le transfert d&#39;&eacute;lectrons entre les enzymes et l&#39;&eacute;lectrode Au-RGO/Chit a propos&eacute; sa promesse pour la construction de graph&egrave;ne roman bas&eacute; d&eacute;shydrog&eacute;nase biocapteurs.

Oxydation catalytique et la d&eacute;termination des &beta;-NADH utilisant auto-assemblage hybride de nanoparticules d&#39;or et de graph&egrave;ne.

A Selbstmontage Hybrid von gold-Nanopartikeln auf Graphen ver&auml;ndert Elektroden f&uuml;r niedrig-Potenzial NADH Erkennung erreicht worden ist. Wir haben das nat&uuml;rliche Polymer-Chitosan (Chit) unterst&uuml;tzen die Stabilisierung des Graphen in w&auml;ssriger L&ouml;sung, und die elektronegativen Au-Nanopartikeln (NPs) durch elektrostatische Anziehung zu immobilisieren. Die Synergie von Au NPs mit Graphen f&uuml;r katalytische Oxidation von NADH die overpotential ca. 220 mV weniger positiv als die auf der blo&szlig;en Elektrode gebildet und bemerkenswert erh&ouml;ht die aktuellen Oxidation. Die amperometrisch-Sensoren, die auf der Grundlage solcher ge&auml;ndert Elektroden f&uuml;r die Erkennung von NADH stellte eine gute Linearit&auml;t von 1,5 bis 320 &mu;M und zeigte hohen Empfindlichkeit mit einer niedrigen Nachweisgrenze von 1,2 &mu;M (S/N = 3). Es k&ouml;nnten auch gemeinsame st&ouml;renden Elektroaktive Substanzen wie Ascorbins&auml;ure und besa&szlig; gute Reproduzierbarkeit und operative Stabilit&auml;t ausschlie&szlig;en. So herausragende Leistung des Films Au-RGO/Chit sowie die F&auml;higkeit des Graphen, den Elektronen-Transfer zwischen Enzymen und der Elektrode erheblich verbessern schlug ihr Versprechen zur Konstruktion von Roman Graphen-basierte Dehydrogenase Biosensoren.

Katalytische Oxidation und Bestimmung von &beta;-NADH mit Selbstmontage Hybrid von gold-Nanopartikeln und Graphen.

A auto-assemblaggio ibrido di nanoparticelle d&#39;oro sul grafene modificato elettrodi per la rilevazione di NADH basso potenziale &egrave; stato raggiunto. Abbiamo usato il polimero naturale chitosano (Chit) per assistere la stabilizzazione di grafene in soluzione acquosa e immobilizzare elettronegative Au nanoparticelle (NPs) attraverso attrazione elettrostatica. La sinergia di Au NPs con grafene per ossidazione catalitica del NADH fatto overpotential ca. 220 mV meno positivo rispetto a quello sull&#39;elettrodo nuda e aumentato notevolmente la corrente di ossidazione. I sensori amperometrico basati su tale modifica elettrodi per rilevazione di NADH esibito una buona linearit&agrave; da 1,5 a 320 &mu;M e ha mostrato ad alta sensibilit&agrave; con un basso limite di 1,2 &mu;M (S/N = 3). Potrebbero anche escludere comuni interferenti elettroattivi composti come l&#39;acido ascorbico e posseduto buona riproducibilit&agrave; e stabilit&agrave; di funzionamento. Tali prestazioni eminente del film Au-RGO/Chit insieme alla capacit&agrave; di grafene per migliorare notevolmente il trasferimento di elettroni tra gli enzimi e l&#39;elettrodo ha suggerito la promessa per la costruzione di biosensori deidrogenasi grafene romanzo basato.

Ossidazione catalitica e determinazione della &beta;-NADH utilizzando l&#39;auto-assemblaggio ibrido di nanoparticelle d&#39;oro e di grafene.

A &#x81EA;&#x5DF1;&#x7D44;&#x7E54;&#x5316;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x4E0A;&#x91D1;&#x30CA;&#x30CE;&#x7C92;&#x5B50;&#x306E;&#x30CF;&#x30A4;&#x30D6;&#x30EA;&#x30C3;&#x30C9;&#x306E;&#x5909;&#x66F4;&#x306E;&#x96FB;&#x6975;&#x3092;&#x4F4E;&#x96FB;&#x4F4D; NADH &#x691C;&#x51FA;&#x3092;&#x9054;&#x6210;&#x3002;&#x6C34;&#x6EB6;&#x6DB2;&#x4E2D;&#x3067;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x306E;&#x5B89;&#x5B9A;&#x5316;&#x3092;&#x652F;&#x63F4;&#x3057;&#x3001;&#x9759;&#x96FB;&#x5F15;&#x529B;&#x3092;&#x901A;&#x3058;&#x3066;&#x9670;&#x6027; Au &#x30CA;&#x30CE;&#x7C92;&#x5B50; (NPs) &#x3092;&#x52D5;&#x3051;&#x306A;&#x304F;&#x5929;&#x7136;&#x9AD8;&#x5206;&#x5B50;&#x30AD;&#x30C8;&#x30B5;&#x30F3; &#xFF08;&#x4F1D;&#x7968;&#xFF09; &#x3092;&#x4F7F;&#x7528;&#x3057;&#x307E;&#x3059;&#x3002;Au NPs &#x306E;&#x76F8;&#x4E57;&#x52B9;&#x679C;&#x306E; NADH &#x306E;&#x9178;&#x5316;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x3068;&#x904E;&#x96FB;&#x5727; ca&#x3002; 220 mV &#x4EE5;&#x4E0B;&#x306E;&#x967D;&#x6027;&#x3088;&#x308A;&#x3082;&#x88F8;&#x306E;&#x96FB;&#x6975;&#x306B;&#x3001;&#x9178;&#x5316;&#x96FB;&#x6D41;&#x3092;&#x8457;&#x3057;&#x304F;&#x5897;&#x52A0;&#x3057;&#x307E;&#x3059;&#x3002;NADH &#x306E;&#x691C;&#x51FA;&#x306F; 320 &mu; m 1.5 &#x304B;&#x3089;&#x306E;&#x826F;&#x597D;&#x306A;&#x76F4;&#x7DDA;&#x6027;&#x3092;&#x5C55;&#x793A;&#x3057;&#x3001;&#x9AD8;&#x611F;&#x5EA6; 1.2 &mu; M &#x306E;&#x4F4E;&#x691C;&#x51FA;&#x9650;&#x754C;&#x3092;&#x793A;&#x3057;&#x305F;&#x3088;&#x3046;&#x306B;&#x57FA;&#x3065;&#x304F;&#x30A2;&#x30F3;&#x30DA;&#x30ED; &#x30E1;&#x30C8;&#x30EA;&#x30C3;&#x30AF; &#x30BB;&#x30F3;&#x30B5;&#x30FC;&#x96FB;&#x6975;&#x3092;&#x5909;&#x66F4; (S/N = 3)&#x3002;&#x30A2;&#x30B9;&#x30B3;&#x30EB;&#x30D3;&#x30F3;&#x9178;&#x3068;&#x4FDD;&#x6709;&#x826F;&#x3044;&#x518D;&#x73FE;&#x6027;&#x3068;&#x5B89;&#x5B9A;&#x904B;&#x7528;&#x306E;&#x3088;&#x3046;&#x306A;&#x4E00;&#x822C;&#x7684;&#x306A;&#x5E72;&#x6E09;&#x30B2;&#x30EB;&#x30ED;&#x30DC;&#x30C3;&#x30C8;&#x5316;&#x5408;&#x7269;&#x3092;&#x9664;&#x5916;&#x3059;&#x308B;&#x3053;&#x3068;&#x3082;&#x3067;&#x304D;&#x307E;&#x305B;&#x3093;&#x3067;&#x3057;&#x305F;&#x3002;Au-RGO/&#x30E2;&#x30FC;&#x30C1;&#x30C3;&#x30C8;&#x819C;&#x9175;&#x7D20;&#x3068;&#x96FB;&#x6975;&#x9593;&#x306E;&#x96FB;&#x5B50;&#x79FB;&#x52D5;&#x304C;&#x5927;&#x5E45;&#x306B;&#x5F37;&#x5316;&#x3059;&#x308B;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x306E;&#x6A5F;&#x80FD;&#x3068;&#x5171;&#x306B;&#x3053;&#x306E;&#x3088;&#x3046;&#x306A;&#x8457;&#x540D;&#x306A;&#x6027;&#x80FD;&#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;&#x5C0F;&#x8AAC;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x8131;&#x6C34;&#x7D20;&#x9175;&#x7D20;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30BB;&#x30F3;&#x30B5;&#x30FC;&#x3092;&#x69CB;&#x7BC9;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x306F;&#x3001;&#x305D;&#x306E;&#x7D04;&#x675F;&#x3092;&#x793A;&#x5506;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;

&#x89E6;&#x5A92;&#x9178;&#x5316;&#x3068;&#x81EA;&#x5DF1;&#x7D44;&#x7E54;&#x5316;&#x91D1;&#x30CA;&#x30CE;&#x7C92;&#x5B50;&#x3068;&#x30B0;&#x30E9;&#x30D5;&#x30A7;&#x30F3;&#x306E;&#x30CF;&#x30A4;&#x30D6;&#x30EA;&#x30C3;&#x30C9;&#x3092;&#x7528;&#x3044;&#x305F; &beta; NADH &#x306E;&#x5B9A;&#x91CF;&#x3002;

A &#xC800; &#xC7A0;&#xC7AC;&#xB825; NADH &#xD0D0;&#xC9C0;&#xB97C; &#xB2EC;&#xC131; &#xADF8;&#xB798;&#xC5D0; &#xAE08; &#xB098;&#xB178; &#xC785;&#xC790;&#xC758; &#xD558;&#xC774;&#xBE0C;&#xB9AC;&#xB4DC; &#xC804;&#xADF9; &#xC218;&#xC815; &#xD558;&#xB294; &#xC790;&#xAE30; &#xC870;&#xB9BD;. &#xC218;&#xC131; &#xC194;&#xB8E8;&#xC158;&#xC5D0; &#xADF8;&#xB798;&#xC758; &#xC548;&#xC815;&#xD654;&#xB97C; &#xC9C0;&#xC6D0; &#xD558; &#xACE0; &#xC815;&#xC804;&#xAE30; &#xB9E4;&#xB825;&#xC744; &#xD1B5;&#xD574; electronegative Au &#xB098;&#xB178; &#xC785;&#xC790; (NPs) &#xBB34;&#xB825;&#xD654;&#xB97C; &#xCC9C;&#xC5F0; &#xACE0;&#xBD84;&#xC790; &#xD0A4;&#xD1A0; &#xC0B0; (&#xC804;&#xD45C;)&#xC744; &#xC0AC;&#xC6A9; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. NADH&#xC758; &#xCD09;&#xB9E4; &#xC0B0;&#xD654;&#xC5D0; &#xB300; &#xD55C; &#xADF8;&#xB798;&#xC640; Au Nps&#xC758; &#xC2DC;&#xB108;&#xC9C0; &#xB9E8; &#xC804;&#xADF9;&#xC5D0; overpotential ca. 220 mV &#xBCF4;&#xB2E4; &#xAE0D;&#xC815;&#xC801;&#xC778; &#xB35C; &#xB9CC;&#xB4E4;&#xC5C8;&#xACE0; &#xB208;&#xC5D0; &#xB744;&#xAC8C; &#xD604;&#xC7AC; &#xC0B0;&#xD654;&#xB97C; &#xC99D;&#xAC00;. Amperometric &#xC13C;&#xC11C; &#xAE30;&#xBC18; &#xB4F1;&#xC73C;&#xB85C; &#xC804;&#xADF9; &#xC218;&#xC815; NADH&#xC758; &#xAC80;&#xCD9C; 320 &mu; M&#xC5D0; 1.5&#xC5D0;&#xC11C; &#xC88B;&#xC740; &#xC120;&#xD615;&#xC131;&#xC744; &#xC804;&#xC2DC; &#xD558; &#xACE0; &#xB192;&#xC740; &#xAC10;&#xB3C4;&#xC640; 1.2 &mu; M&#xC758; &#xB0AE;&#xC740; &#xAC80;&#xCD9C; &#xD55C;&#xACC4;&#xB97C; &#xBCF4;&#xC5EC;&#xC8FC;&#xC5C8;&#xB2E4; (S/N = 3). Ascorbic &#xC0B0; &#xBC0F; &#xBCF4;&#xC720; &#xC88B;&#xC740; &#xC7AC;&#xD604;&#xC131; &#xBC0F; &#xC870;&#xC791; &#xC0C1; &#xC548;&#xC815;&#xC131; &#xAC19;&#xC740; &#xC77C;&#xBC18;&#xC801;&#xC778; &#xAC04;&#xC12D; electroactive &#xD654;&#xD569;&#xBB3C; &#xC81C;&#xC678;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB798; &#xC218; &#xD6A8;&#xC18C;&#xC640; &#xC804;&#xADF9; &#xC0AC;&#xC774;&#xC758; &#xC804;&#xC790; &#xC774;&#xB3D9;&#xC774; &#xD6E8;&#xC52C; &#xD5A5;&#xC0C1; &#xB418;&#xBBC0;&#xB85C; &#xD568;&#xAED8; &#xB204;&#xAD6C;&#xB098;-RGO/&#xC804;&#xD45C; &#xC601;&#xD654; &#xAC19;&#xC740; &#xC800;&#xBA85;&#xD55C; &#xC131;&#xB2A5; &#xAE30;&#xBC18; &#xC18C;&#xC124; &#xADF8;&#xB798; &#xD6A8;&#xC18C; biosensors&#xB97C; &#xC0DD;&#xC131; &#xD558;&#xB294; &#xB370; &#xADF8; &#xC57D;&#xC18D;&#xC744; &#xC81C;&#xC548; &#xD588;&#xB2E4;.

&#xCD09;&#xB9E4; &#xC0B0;&#xD654; &#xBC0F; &beta;-NADH &#xC790;&#xAE30; &#xC870;&#xB9BD; &#xAE08; &#xB098;&#xB178; &#xC785;&#xC790;&#xC640; &#xADF8;&#xB798; &#xD558;&#xC774;&#xBE0C;&#xB9AC;&#xB4DC;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC;&#xC758; &#xACB0;&#xC815;.

A autoensamblaje h&iacute;brido de nanopart&iacute;culas de oro en grafeno electrodos modificados para detecci&oacute;n de NADH de baja potencia se ha logrado. Utilizamos el quitosano de pol&iacute;mero natural (Chit) para ayudar a la estabilizaci&oacute;n del grafeno en soluci&oacute;n acuosa e inmovilizar las nanopart&iacute;culas electronegativas (NPs) a trav&eacute;s de la atracci&oacute;n electrost&aacute;tica. La sinergia de Au NPs con grafeno para oxidaci&oacute;n catal&iacute;tica de la NADH overpotential aprox. 220 mV menos positivos que en el electrodo desnudo y aument&oacute; notablemente la oxidaci&oacute;n actual. Los sensores amperom&eacute;tricos basados en tales electrodos modificaci&oacute;n para detecci&oacute;n de NADH exhibi&oacute; una buena linealidad de 1,5 a 320 &mu;M y mostr&oacute; alta sensibilidad con un l&iacute;mite de detecci&oacute;n baja 1.2 &mu;m (S/N = 3). Tambi&eacute;n podr&iacute;an excluir comunes que interfieren electroactivos compuestos como el &aacute;cido asc&oacute;rbico y pose&iacute;a buena reproducibilidad y estabilidad operacional. Dichos resultados eminentes de la pel&iacute;cula de Au-RGO/Chit junto con la capacidad de grafeno para mejorar significativamente la transferencia de electrones entre el electrodo y enzimas sugirieron su promesa para la construcci&oacute;n de la novela grafeno basado deshidrogenasa biosensores.

Oxidaci&oacute;n catal&iacute;tica y determinaci&oacute;n de &beta;-NADH mediante autoensamblaje h&iacute;brido de nanopart&iacute;culas de oro y el grafeno.

During cortical development, Cajal-Retzius (CR) cells are among the earliest-born subclasses of neurons. These enigmatic neurons play an important role in cortical development through their expression of the extracellular protein, reelin. CR cells arise from discrete sources within the telencephalon, including the pallial-subpallial border and the medial (cortical hem) regions of the pallium. Combined evidence suggests that CR cells derived from distinct origins may have different distributions and functions. By tracing CR cells derived from the cortical hem using the inducible Cre transgenic mouse tool, Frizzled 10-CreER™, we examined the specific properties of hem-derived CR cells during cortical development. Our results show that the progenitor zone for later production of CR cells from the hem can be specifically marked as early as embryonic day 6.5 (E6.5), a pre-neural period. Moreover, using our Cre line, we found that some hem-derived CR cells migrated out along the fimbrial radial glial scaffold, which was also derived from the cortical hem, and preferentially settled in the hippocampal marginal zone, which indicated specific roles for hem-derived CR cells in hippocampal development.

Inducible genetic lineage tracing of cortical hem derived Cajal-Retzius cells reveals novel properties.

In this study, the new nanocomposites of beta-cyclodextrin (beta-CD) and multi-walled carbon nanotubes (MWNTs) have been prepared and deposited on the indium tin oxide (ITO) electrodes to form the beta-CD/MWNTs modified ITO electrodes. These novel modified electrodes exhibited the abilities to lower the electrooxidation potentials of NADH substantially (ca. 600 mV) in comparison with bare ITO electrodes. Furthermore, a linear response to NADH in the concentration range of 4.0 x 10(-6) to 3.2 x 10(-3) mol/L was observed, with a detection limit of 8.0 x 10(-7) mol/L. Such ability of the novel nanocomposites to promote the electron-transfer reaction of NADH suggests great promise for dehydrogenase-based amperometric biosensors.

Electrocatalysis for the oxidation of NADH based on beta-cyclodextrin/multi-walled carbon nanotubes modified ITO electrode.

Classical major histocompatibility complex (MHC) class I, first identified in the immune system, is also expressed in the developing and adult central nervous system (CNS). Although the MHC class I molecules have been found to be expressed in the CNS of different species, a necessary step to elucidate the temporal and spatial expression patterns of MHC class I molecules in the brain development has never been taken. Frozen sections were made from the brains of embryonic and postnatal C57BL/6 J mice, and the expression of H-2D(b) mRNA was examined by in situ hybridization. Immunofluorescence was also performed to define the cell types that express H2-D(b) in P15 mice. At E10.5, the earliest stage we examined, H2-D(b) was expressed in neuroepithelium of the brain vesicles. From E12.5 to P0, H2-D(b) expression was mainly located at cerebral cortex, neuroepithelium of the lateral ventricle, neuroepithelium of aquaeductus and developing cerebellum. From P4 to adult, H2-D(b) mRNA was detected at olfactory bulb, hippocampus, cerebellum and some nerve nuclei. The major cell types expressing H-2D(b) in P15 hippocampus, cerebral cortex and olfactory bulb were neuron. H2-K(b) signal paralleled that of H2-D(b) and the expression levels of the two molecules were comparable throughout the brain. The investigation of the expression pattern of H-2D(b) at both embryonic and postnatal stages is important for further understanding the physiological and pathological roles of H2-D(b) in the developing CNS.

The expression pattern of classical MHC class I molecules in the development of mouse central nervous system.

Interkinetic nuclear migration (INM) is a key feature of cortical neurogenesis. INM functions to maximize the output of the neuroepithelium, and more importantly, balance the self-renewal and differentiation of the progenitors. Although INM has been reported to be highly correlated with the cell cycle, little is known about the effects of cell cycle regulators on INM. In this study, by crossing Foxm1(fl/fl) mice with Emx1-Cre line, we report that a conditional disruption of forkhead transcription factor M1 (Foxm1) in dorsal telencephalon results in abnormal cell cycle progression, leading to impaired INM through the downregulation of Cyclin b1 and Cdc25b. The impairment of INM disturbs the synchronization of apical progenitors (APs) and promotes the transition from APs to basal progenitors (BPs) in a cell-autonomous fashion. Moreover, ablation of Foxm1 causes anxiety-related behaviors in adulthood. Thus, this study provides evidence of linkages among the cell cycle regulator Foxm1, INM, and adult behavior.

A novel function for Foxm1 in interkinetic nuclear migration in the developing telencephalon and anxiety-related behavior.

The rodent barrel cortex has been established as an ideal model for studying the development and plasticity of a neuronal circuit. The barrel cortex consists of barrel and septa columns, which receive various input signals through distinct pathways. The lemniscal pathway transmits whisker-specific signals to homologous barrel columns, and the paralemniscal pathway transmits multi-whisker signals to both barrel and septa columns. The integration of information from both lemniscal and paralemniscal pathways in the barrel cortex is critical for precise object recognition. As the main target of the posterior medial nucleus (POm) in the paralemniscal pathway, layer 5a (L5a) pyramidal neurons are involved in both barrel and septa circuits and are considered an important site of information integration. However, information on L5a neurons is very limited. This study aims to explore the cellular features of L5a neurons and to provide a morphological basis for studying their roles in the development of the paralemniscal pathway and in information integration.

Calretinin-positive L5a pyramidal neurons in the development of the paralemniscal pathway in the barrel cortex.

The epithalamus, which is dorsal to the thalamus, consists of the habenula, pineal gland and third ventricle choroid plexus and plays important roles in the stress response and sleep-wake cycle in vertebrates. During development, the epithalamus arises from the most dorsal part of prosomere 2. However, the mechanism underlying epithalamic development remains largely unknown. Foxg1 is critical for the development of the telencephalon, but its role in diencephalic development has been under-investigated. Patients suffering from FOXG1-related disorders exhibit severe anxiety, sleep disturbance and choroid plexus cysts, indicating that Foxg1 likely plays a role in epithalamic development. In this study, we identified the specific expression of Foxg1 in the developing epithalamus. Using a "self-deletion" approach, we found that the habenula significantly expanded and included an increased number of habenular subtype neurons. The innervations, particularly the habenular commissure, were severely impaired. Meanwhile, the Foxg1 mutants exhibited a reduced pineal gland and more branched choroid plexus. After ablation of Foxg1 no obvious changes in Shh and Fgf signalling were observed, suggesting that Foxg1 regulates the development of the epithalamus without the involvement of Shh and Fgfs. Our findings provide new insights into the regulation of the development of the epithalamus.

Foxg1 deletion impairs the development of the epithalamus.

During early development, signaling centers, such as the cortical hem and the preoptic area (POA), are critical for telencephalic patterning. However, the mechanisms underlying the maintenance of signal centers are poorly understood. Here, we report that the transcription factor Foxg1 is required to confine the POA, a resource of Sonic Hedgehog (Shh) that is pivotal for ventral telencephalic development. Cell-specific deletion of Foxg1 achieved by crossing Foxg1fl/fl with Dbx1-cre or Nestin-CreER combined with tamoxifen induction results in a dramatic expansion of the POA accompanied by the significantly increased activity of the Shh signaling pathway. Ventral pattern formation was severely impaired. Moreover, we demonstrated that Foxg1 directly represses Dbx1 to restrict the POA. Furthermore, we found that the ventral pallium was expanded, which might also contribute to the observed patterning defects. These findings will improve our understanding of the maintenance of signal centers and help to elucidate the mechanisms underlying ventral telencephalic patterning.

Foxg1 Directly Represses Dbx1 to Confine the POA and Subsequently Regulate Ventral Telencephalic Patterning.

The six-layered neocortex consists of diverse neuron subtypes. Deeper-layer neurons originate from apical progenitors (APs), while upper-layer neurons are mainly produced by basal progenitors (BPs), which are derivatives of APs. As development proceeds, an AP generates two daughter cells that comprise an AP and a deeper-layer neuron or a BP. How the transition of APs to BPs is spatiotemporally regulated is a fundamental question. Here, we report that conditional deletion of phoshpoinositide-dependent protein kinase 1 (PDK1) in mouse developing cortex achieved by crossing Emx1Cre line with Pdk1fl/fl leads to a delayed transition of APs to BPs and subsequently causes an increased output of deeper-layer neurons. We demonstrate that PDK1 is involved in the modulation of the aPKC-Par3 complex and further regulates the asymmetric cell division (ACD). We also find Hes1, a downstream effecter of Notch signal pathway is obviously upregulated. Knockdown of Hes1 or treatment with Notch signal inhibitor DAPT recovers the ACD defect in the Pdk1 cKO. Thus, we have identified a novel function of PDK1 in controlling the transition of APs to BPs.

PDK1 Regulates Transition Period of Apical Progenitors to Basal Progenitors by Controlling Asymmetric Cell Division.

The Wnt signaling pathway plays key roles in various developmental processes. Wnt5a, which activates the non-canonical pathway, has been shown to be particularly important for axon guidance and outgrowth as well as dendrite morphogenesis. However, the mechanism underlying the regulation of Wnt5a remains unclear. Here, through conditional disruption of Foxg1 in hippocampal progenitors and postmitotic neurons achieved by crossing Foxg1 with Emx1-Cre and Nex-Cre, respectively, we found that Wnt5a rather than Wnt3a/Wnt2b was markedly upregulated. Overexpression of Foxg1 had the opposite effects along with decreased dendritic complexity and reduced mossy fibers in the hippocampus. We further demonstrated that FOXG1 directly repressed Wnt5a by binding to its promoter and one enhancer site. These results expand our knowledge of the interaction between Foxg1 and Wnt signaling and help elucidate the mechanisms underlying hippocampal development.

FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus.

Nucleotide oligomerization domain-like receptors (NLRs), belonging to a large family of pattern recognition receptors, participate in the host's first line of defense against invading pathogens. Caspase recruitment domain containing 5 (NLRC5), the largest member in the NLR family, is demonstrated to be involved in the innate immune response and inflammatory diseases far and wide. Recent studies report that NLRC5 is associated with some central nervous system (CNS) diseases. Besides, NLRC5 is a mastery regulator for the expression of MHC class I both in the immune system and the CNS, while MHC class I is expressed and exerts its function in the brain. Therefore, it is necessary to investigate the expression pattern of NLRC5 in the developing and adult CNS. In our study, postnatal brain sections of C57BL/6 J mice are analyzed for the expression of NLRC5 protein by immunofluorescence. In the postnatal stages of developing telencephalon, NLRC5 exhibits a spatial and temporal expression pattern. NLRC5 is time-specifically expressed in subfields of hippocampus and different layers of prefrontal cortex. Moreover, it is shown that NLRC5 is highly cell type specific. It can be expressed in large quantities by neurons and microglia, but rarely expressed by astrocytes. Taken together, our research is important for further understanding the biological characteristics of NLRC5 and its function in the CNS.

Expression pattern of NLRC5 in the postnatal mouse brain.

T helper (Th) cell imbalances have been associated with the pathophysiology of sepsis, including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Cold-inducible RNA-binding protein (CIRP), a novel damage-associated molecular pattern (DAMP) was reported that could induce T cell activation, and skew CD4 T cells towards a Th1 profile. However, the effect and underlying mechanisms of CIRP on Th17/Treg differentiation in sepsis still remains unknown.

CIRP increases Foxp3 regulatory T cells and inhibits development of Th17 cells by enhancing TLR4-IL-2 signaling in the late phase of sepsis.

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury.

Article	Year
Catalytic oxidation and determination of Î²-NADH using self-assembly hybrid of gold nanoparticles and graphene. The Analyst\| PubMed ID: 21594262	2011
Inducible genetic lineage tracing of cortical hem derived Cajal-Retzius cells reveals novel properties. PloS one\| PubMed ID: 22174859	2011
Electrocatalysis for the oxidation of NADH based on beta-cyclodextrin/multi-walled carbon nanotubes modified ITO electrode. Journal of nanoscience and nanotechnology\| PubMed ID: 22755011	2012
The expression pattern of classical MHC class I molecules in the development of mouse central nervous system. Neurochemical research\| PubMed ID: 23161087	2013
A novel function for Foxm1 in interkinetic nuclear migration in the developing telencephalon and anxiety-related behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 24453338	2014
Calretinin-positive L5a pyramidal neurons in the development of the paralemniscal pathway in the barrel cortex. Molecular brain\| PubMed ID: 25404384	2014
Foxg1 deletion impairs the development of the epithalamus. Molecular brain\| PubMed ID: 29394901	2018
Foxg1 Directly Represses Dbx1 to Confine the POA and Subsequently Regulate Ventral Telencephalic Patterning. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 30843579	2019
PDK1 Regulates Transition Period of Apical Progenitors to Basal Progenitors by Controlling Asymmetric Cell Division. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 31504280	2020
FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus. Neuroscience bulletin\| PubMed ID: 33389683	2021
Expression pattern of NLRC5 in the postnatal mouse brain. Acta histochemica\| PubMed ID: 35952483	2022
CIRP increases Foxp3 regulatory T cells and inhibits development of Th17 cells by enhancing TLR4-IL-2 signaling in the late phase of sepsis. International immunopharmacology\| PubMed ID: 38531201	2024
Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 39119837	2024

Xiaojing Wu

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