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1.
Elife ; 122024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607670

RESUMO

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.


Assuntos
Envelhecimento , Células-Tronco Neurais , Adulto , Recém-Nascido , Humanos , Divisão Celular , Hipocampo , Homeostase
2.
J Am Chem Soc ; 144(31): 14396-14402, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35894835

RESUMO

The first asymmetric total synthesis of (+)-alstonlarsine A has been realized. The prominent features of the current synthesis include the following: (i) a Pd/self-adaptable ligand complex-catalyzed asymmetric allylic alkylation of 2-methyl-2-cyclopentenyl carbonate with 2-indolylsubstituted dimethyl malonate to establish the key stereocenter of C15, (ii) an intramolecular nitrile oxide-alkene [3 + 2] cycloaddition (INOC [3 + 2]) to construct the cyclohepta[b]indole backbone with the installment of the requisite stereochemistry of the all-carbon quaternary center of C20, and (iii) a late-stage interrupted Pictet-Spengler reaction (IPSR) to rapidly assemble the core structure of (+)-alstonlarsine A.


Assuntos
Catálise , Alquilação
3.
Sci Adv ; 8(9): eabl7263, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35245119

RESUMO

Evolutionary mutations in primate-specific genes drove primate cortex expansion. However, whether conserved genes with previously unidentified functions also play a key role in primate brain expansion remains unknown. Here, we focus on BRN2 (POU3F2), a gene encoding a neural transcription factor commonly expressed in both primates and mice. Compared to the limited effects on mouse brain development, BRN2 biallelic knockout in cynomolgus monkeys (Macaca fascicularis) is lethal before midgestation. Histology analysis and single-cell transcriptome show that BRN2 deficiency decreases RGC expansion, induces precocious differentiation, and alters the trajectory of neurogenesis in the telencephalon. BRN2, serving as an upstream factor, controls specification and differentiation of ganglionic eminences. In addition, we identified the conserved function of BRN2 in cynomolgus monkeys to human RGCs. BRN2 may function by directly regulating SOX2 and STAT3 and maintaining HOPX. Our findings reveal a previously unknown mechanism that BRN2, a conserved gene, drives early primate telencephalon development by gaining novel mechanistic functions.

4.
Biomed Res Int ; 2020: 4374801, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33457408

RESUMO

Dracocephalum tanguticum and Dracocephalum moldavica are important herbs from Lamiaceae and have great medicinal value. We used the Illumina sequencing technology to sequence the complete chloroplast genome of D. tanguticum and D. moldavica and then conducted de novo assembly. The two chloroplast genomes have a typical quadripartite structure, with the gene's lengths of 82,221 bp and 81,450 bp, large single-copy region's (LSC) lengths of 82,221 bp and 81,450 bp, and small single-copy region's (SSC) lengths of 17,363 bp and 17,066 bp, inverted repeat region's (IR) lengths of 51,370 bp and 51,352 bp, respectively. The GC content of the two chloroplast genomes was 37.80% and 37.83%, respectively. The chloroplast genomes of the two plants encode 133 and 132 genes, respectively, among which there are 88 and 87 protein-coding genes, respectively, as well as 37 tRNA genes and 8 rRNA genes. Among them, the rps2 gene is unique to D. tanguticum, which is not found in D. moldavica. Through SSR analysis, we also found 6 mutation hotspot regions, which can be used as molecular markers for taxonomic studies. Phylogenetic analysis showed that Dracocephalum was more closely related to Mentha.


Assuntos
Cloroplastos/metabolismo , Genes de Plantas , Genoma de Cloroplastos , Lamiaceae/genética , Plantas Medicinais/genética , Sequenciamento Completo do Genoma , Composição de Bases , Genoma de Planta , Sequenciamento de Nucleotídeos em Larga Escala , Repetições de Microssatélites , Mutação , Filogenia , RNA de Transferência/metabolismo , Análise de Sequência de DNA
5.
J Org Chem ; 82(11): 5557-5565, 2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28497692

RESUMO

We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted pyrrolidines from pyrrolidine by two rounds of redox-triggered α-C-H functionalization. Although this approach can be used to introduce substituents at the 2- and 5-positions, it is lengthy because the redox auxiliary must be removed and then reinstalled. Therefore, we sought to develop a method to oxidize 2-functionalized pyrrolidine to cyclic N,O-acetal which could then react with a nucleophile for introduction of the 5-substituent. In this work, we found that molecular iodine can mediate the preferential oxidation of secondary over tertiary α-C-H bonds of α-substituted pyrrolidines to form cyclic N,O-acetals, improving the step economy of our previously reported method. With this strategy, (±)-preussin and its C(3) epimer were synthesized from (±)-pyrrolidin-3-ol.

6.
Anal Chem ; 88(10): 5507-12, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27094518

RESUMO

The organic thin-film fluorescence probe, with the advantages of not polluting the analyte and fast response, has attracted much attention in explosive detection. Different with nitro explosives, the peroxide-based explosives are hardly to be detected because of their poor ultraviolet absorption and lack of an aromatic ring. As the signature compound of peroxide-based explosives, H2O2 vapor detection became more and more important. Boron ester or acid is considered to be a suitable functional group for the detection of hydrogen peroxide due to its reliable reactive activity. Its only drawback lies on its slow degradation velocity. In this work, we try to introduce some functional group to make the boron ester to be easily oxidized by H2O2. Herein, 4-(phenyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)benzaldehyde (OTB) was synthesized and its imine derivatives, OTBXAs, were easily obtained just by putting OTB films in different primary amines vapors. OTBXAs show fast deboronation velocity in H2O2 vapor compared with OTB. The complete reaction time of (E)-N-phenyl-4-((propylimino)methyl)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)aniline (OTBPA) was even shortened 40 times with a response time of seconds. The detection limit for H2O2 vapor was as low as 4.1 parts per trillion (ppt). Further study showed that it is a general approach to enhance the sensing performance of borate to hydrogen peroxide (H2O2) vapor by introducing an imine into an aromatic borate molecule via a solid/vapor reaction.


Assuntos
Boro/química , Peróxido de Hidrogênio/análise , Bases de Schiff/química , Espectrometria de Fluorescência , Ácidos Borônicos/química , Corantes Fluorescentes/química , Gases/química , Iminas/química , Limite de Detecção , Oxirredução , Teoria Quântica
7.
Anal Chem ; 88(4): 2497-501, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26776457

RESUMO

Sarin, used as chemical warfare agents (CWAs) for terrorist attacks, can induce a number of virulent effects. Therefore, countermeasures which could realize robust and convenient detection of sarin are in exigent need. A concise charge-transfer colorimetric and fluorescent probe (4-(6-(tert-butyl)pyridine-2-yl)-N,N-diphenylaniline, TBPY-TPA) that could be capable of real-time and on-site monitoring of DCP vapor was reported in this contribution. Upon contact with DCP, the emission band red-shifted from 410 to 522 nm upon exposure to DCP vapor. And the quenching rate of TBPY-TPA reached up to 98% within 25 s. Chemical substances such as acetic acid (HAc), dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PAMP), and triethyl phosphate (TEP) do not interfere with the detection. A detection limit for DCP down to 2.6 ppb level is remarkably achieved which is below the Immediately Dangerous to Life or Health concentration. NMR data suggested that a transformation of the pyridine group into pyridinium salt via a cascade reaction is responsible for the sensing process which induced the dramatic fluorescent red shift. All of these data suggest TBPY-TPA is a promising fluorescent sensor for a rapid, simple, and low-cost method for DCP detection, which could be easy to prepare as a portable chemosensor kit for its practical application in real-time and on-site monitoring.


Assuntos
Compostos de Anilina/química , Substâncias para a Guerra Química/análise , Corantes Fluorescentes/análise , Compostos Organofosforados/análise , Piridinas/química , Substâncias para a Guerra Química/química , Colorimetria , Corantes Fluorescentes/química , Estrutura Molecular , Compostos Organofosforados/química , Volatilização
8.
Org Lett ; 17(19): 4758-61, 2015 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-26378343

RESUMO

By using o-benzoquinone as an internal oxidant, the regio- and diastereoselective functionalization of the secondary over the tertiary α-C-H bond of 2-substituted pyrrolidines is first realized. Subsequent intermolecular addition of a nucleophile to the generated N,O-acetal and cleavage of the aromatic substituent leads to 2,5-disubstituted pyrrolidines.

9.
Chem Commun (Camb) ; 51(54): 10868-70, 2015 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-26054635

RESUMO

A simple, highly stable, sensitive and selective fluorescent system for peroxide explosives was developed via an aromatic aldehyde oxidation reaction. The high efficiency arises from its higher HOMO level and multiple H-bonding. The sensitivity is obtained to be 0.1 ppt for H2O2 and 0.2 ppb for TATP.


Assuntos
Aminas/química , Substâncias Explosivas/análise , Gases/química , Peróxido de Hidrogênio/análise , Fenóis/química , Espectrometria de Fluorescência , Compostos Heterocíclicos com 1 Anel/análise , Oxirredução , Peróxidos/análise , Teoria Quântica
10.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 9): m1160-1, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22969459

RESUMO

The title compound, (C(5)H(7)N(2))(2)[CdI(4)]·H(2)O, contains one [CdI(4)](2-) anion, two prontonated 4-amino-pyridine mol-ecules and one water mol-ecule in the asymmetric unit. In the anion, the Cd(II) atom is coordinated by four I atoms in a slightly distorted tetra-hedral geometry. The [CdI(4)](2-) anion and the water mol-ecule are bis-ected by a crystallographic mirror plane perpendicular to the c-axis direction, with the Cd(II) atom, two of the I atoms and the atoms of the water mol-ecule located on this plane. The crystal packing is stabilized by inter-molecular N-H⋯I, N-H⋯O and O-H⋯I hydrogen bonds and by π-π stacking inter-actions [centroid-centroid distance = 3.798 (3) Å) between pyridine rings, which build up a three-dimensional network.

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