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1.
Nature ; 583(7818): 771-774, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32728236

RESUMEN

Seeing-the angular size of stellar images blurred by atmospheric turbulence-is a critical parameter used to assess the quality of astronomical sites at optical/infrared wavelengths. Median values at the best mid-latitude sites are generally in the range of 0.6-0.8 arcseconds1-3. Sites on the Antarctic plateau are characterized by comparatively weak turbulence in the free atmosphere above a strong but thin boundary layer4-6. The median seeing at Dome C is estimated to be 0.23-0.36 arcseconds7-10 above a boundary layer that has a typical height of 30 metres10-12. At Domes A and F, the only previous seeing measurements have been made during daytime13,14. Here we report measurements of night-time seeing at Dome A, using a differential image motion monitor15. Located at a height of just 8 metres, it recorded seeing as low as 0.13 arcseconds, and provided seeing statistics that are comparable to those at a height of 20 metres at Dome C. This indicates that the boundary layer was below 8 metres for 31 per cent of the time, with median seeing of 0.31 arcseconds, consistent with free-atmosphere seeing. The seeing and boundary-layer thickness are found to be strongly correlated with the near-surface temperature gradient. The correlation confirms a median thickness of approximately 14 metres for the boundary layer at Dome A, as found from a sonic radar16. The thinner boundary layer makes it less challenging to locate a telescope above it, thereby giving greater access to the free atmosphere.

2.
Proc Natl Acad Sci U S A ; 120(17): e2302448120, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37068250

RESUMEN

The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial biosynthetic enzymes of TAs and especially the characteristic tropane skeletons, we generated the chromosome-level genome assemblies of cocaine-producing Erythroxylum novogranatense (Erythroxylaceae, rosids clade) and hyoscyamine-producing Anisodus acutangulus (Solanaceae, asterids clade). Comparative genomic and phylogenetic analysis suggested that the lack of spermidine synthase/N-methyltransferase (EnSPMT1) in ancestral asterids species contributed to the divergence of polyamine (spermidine or putrescine) methylation in cocaine and hyoscyamine biosynthesis. Molecular docking analysis and key site mutation experiments suggested that ecgonone synthases CYP81AN15 and CYP82M3 adopt different active-site architectures to biosynthesize the same product ecgonone from the same substrate in Erythroxylaceae and Solanaceae. Further synteny analysis showed different evolutionary origins and trajectories of CYP81AN15 and CYP82M3, particularly the emergence of CYP81AN15 through the neofunctionalization of ancient tandem duplication genes. The combination of structural biology and comparative genomic analysis revealed that ecgonone methyltransferase, which is responsible for the biosynthesis of characteristic 2-substituted carboxymethyl group in cocaine, evolved from the tandem copies of salicylic acid methyltransferase by the mutations of critical E216 and S153 residues. Overall, we provided strong evidence for the independent origins of serial TA biosynthetic enzymes on the genomic and structural level, underlying the chemotypic convergence of TAs in phylogenetically distant species.


Asunto(s)
Cocaína , Hiosciamina , Solanaceae , Filogenia , Simulación del Acoplamiento Molecular , Tropanos , Solanaceae/genética , Genómica , Metiltransferasas/genética
3.
Inorg Chem ; 63(2): 1388-1394, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38166363

RESUMEN

By variation of the amount of GeO2, two organic-inorganic hybrid germanoniobate frameworks with 6-connected pcu and 10-connected bct topologies were constructed from peanut-shaped {α-Ge12Nb38} and {ß-Ge12Nb38} clusters, respectively. The {α-Ge12Nb38} and {ß-Ge12Nb38} clusters contain the most Ge centers of germanoniobates reported so far. The compounds exhibit proton conduction properties with a conductivity of 3.04 × 10-4 S·cm-3 for 1 and 1.62 × 10-4 S·cm-3 for 2 at 85 °C and 98% RH. The water vapor adsorption capacities for 1 and 2 are 5.86 and 4.40 mmol·g-1, respectively.

4.
J Integr Plant Biol ; 66(6): 1158-1169, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38517054

RESUMEN

Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity. Given that two C-10 modified camptothecin derivatives, topotecan and irinotecan, have been approved as potent anticancer agents, there is a critical need for methods to access other aromatic ring-functionalized congeners (e.g., C-9, C-10, etc.). However, contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold, thereby limiting the development of modified derivatives. Reported herein, we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa, via metabolomic and transcriptomic analysis. These consist of a cytochrome P450 (NtCPT9H) which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin, as well as two methyltransferases (NtOMT1/2, converting 9-hydroxycamptothecin to 9-methoxycamptothecin), and a uridine diphosphate-glycosyltransferase (NtUGT5, decorating 9-hydroxycamptothecin to 9-ß-D-glucosyloxycamptothecin). Importantly, the critical residues that contribute to the specific catalytic activity of NtCPT9H have been elucidated through molecular docking and mutagenesis experiments. This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering. This will hasten the discovery of novel C-9 modified camptothecin derivatives, with profound implications for pharmaceutical manufacture.


Asunto(s)
Camptotecina , Camptotecina/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo
5.
Inorg Chem ; 62(27): 10675-10683, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37381902

RESUMEN

A 3D Co(III)-complex hybrid polyoxoniobate framework Na10(H2O)36[Co2(phen)2(4,4'-bipy)(Nb6O19)2]·19H2O (1) has been constructed from [Co2(phen)2(4,4'-bipy)(Nb6O19)2]10- dimer units and 2D inorganic Na-O cluster layers. The Co(III) centers are coordinated with {Nb6O19}, 4,4'-bipy and phen simultaneously. The [Co2(phen)2(4,4'-bipy)(Nb6O19)2]10- fragments link the Na-O cluster layers to generate a 3D metal complex-modified hybrid polyoxoniobate framework with π-π interactions between phenanthroline rings. Compound 1 shows reversible thermochromic behavior resulting from electron transfer from {Nb6O19} to 4,4'-bipy and subsequent formation of radical products, which is first observed in polyoxoniobates. Furthermore, the compound exhibits stable nonvolatile storage behavior and rewritable resistive switching with a low switching voltage (1.12 V) and high current on/off ratio (1.18 × 103) along with stable cyclic performance during stability test for 200 cycles. Charge-transfer mechanism has been studied by analyzing the relationship between current and voltage in the process of resistance switching.

6.
Arch Virol ; 168(5): 155, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37145192

RESUMEN

Two new RNA viruses were identified in Ageratum conyzoides in China using high-throughput sequencing, and their genome sequences were determined using PCR and rapid amplification of cDNA ends. The new viruses, which have positive-sense, single-stranded RNA genomes, were provisionally named "ageratum virus 1" (AgV1) and "ageratum virus 2" (AgV2). AgV1 has a genome of 3,526 nucleotides with three open reading frames (ORFs) and shares 49.9% nucleotide sequence identity with the complete genome of Ethiopian tobacco bushy top virus (genus Umbravirus, family Tombusviridae). The genome of AgV2 consists of 5,523 nucleotides and contains five ORFs that are commonly observed in members of the genus Enamovirus of the family Solemoviridae. Proteins encoded by AgV2 exhibited the highest amino acid sequence similarity (31.7-75.0% identity) to the corresponding proteins of pepper enamovirus R1 (an unclassified enamovirus) and citrus vein enation virus (genus Enamovirus). Based on their genome organization, sequence, and phylogenetic relationships, AgV1 is proposed to be a new umbra-like virus of the family Tombusviridae, and AgV2 is proposed to be a new member of the genus Enamovirus of the family Solemoviridae.


Asunto(s)
Ageratum , Luteoviridae , Tombusviridae , Genoma Viral , Filogenia , Tombusviridae/genética , Luteoviridae/genética , Genómica , Nucleótidos , China , Sistemas de Lectura Abierta , Enfermedades de las Plantas , ARN Viral/genética
7.
Plant Dis ; 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37165550

RESUMEN

Calystegia hederacea (Convolvulaceae) is one of the most problematic perennial weeds widely distributed around or in crop fields. Our previous studies showed that C. hederacea is natural reservoir of sweet potato chlorotic stunt virus isolate CH (SPCSV-CH) and sweet potato latent virus (SPLV) (Liu et al. 2020; Zhao et al. 2022). To shed further light on the role of C. hederacea in the epidemiology of sweet potato viruses, in May 2021, a total of seven C. hederacea plants (five asymptomatic, one curling and one mild vein-clearing) were collected from two different sweet potato fields in Xinxiang city of Henan Province in China. Total RNA was prepared from a pool of the seven leaf samples using the EZNA Plant RNA Kit (Omega Bio-Tek, Norcross, GA). A library was constructed from the ribosomal-depleted RNA using the NEBNext Ultra Directional RNA Library Prep Kit for Illumina (NEB, MA, USA) and sequenced using the Illumina HiSeq platform (Novogene, Tianjin, China). A total of 139,057,020 paired-end clean reads of 150 bp were obtained after removing adaptor sequences and low-quality reads and used for de novo assembly using the Trinity (v2.2.0) software. Blast searches of the assembled contigs longer than 200 bp against NCBI nucleotide and protein sequence databases revealed the presence of 37 contigs (237 to 4885 bp) and 19 contigs (261 to 758 bp) with high nucleotide (nt) identity with SPLV and SPCSV-CH, respectively. The occurrence of SPLV and SPCSV-CH on C. hederacea was previously reported, and thus the contig sequences related to SPLV and SPCSV-CH were not subjected to further verification in this study. In addition, one contig (2,827 bp) with the highest nt sequence identity of 94.94% with sweet potato leaf curl Hubei virus (SPLCHbV, genus Begomovirus, family Geminiviridae, accession no. MK931304) was assembled from 16,592 reads, with average coverage depth of 740.5X. These results suggested the presence of SPLCHbV in C. hederacea. To further confirm the RNA sequencing result, each of the seven samples was tested by PCR using partially overlapping (italicized nucleotides) forward and reverse primers (SweeIn-F1, 5`-GGAGGAAGCTAAGTACGAGAATCAGTTAGAG-3`; SweeIn-R1, 5`-GCTTCCTCCTTGTGATTGTAAGTAACATGG-3`) that were designed based on the SPLCHbV-related contig for amplification of circular DNA viral genome (approximately 2.7 kb). Two symptomatic and three symptomless C. hederacea samples were SPLCHbV positive, indicating that virus-like symptoms of the two C. hederacea samples were probably not induced by SPLCHbV. Two of the five amplified products were completely sequenced and deposited to GenBank (accession nos. OQ551733 and OQ551734). Sequences analysis showed that the complete genome sequences of two SPLCHbV C. headrace isolates (2,763 nt and 2,761 nt) had 96.53% nt identity with each other and 95.92 to 97.70% nt identity with that of SPLCHbV isolate Shandong7-2017 (MK931304). In August 2021, fourteen C. hederacea plants (three symptomatic, 11 asymptomatic) collected from natural fields from Zhumadian and Pingdingshan cities in Henan Province, were tested by PCR using SweeIn-F1/R1 primers for SPLCHbV, showing that eight samples were SPLCHbV positive. SPLCHbV belongs to the sweepoviruses, a group of phylogenetically distinct begomoviruses infecting sweet potato, and was reported to infect sweet potato from many provinces of China (Wang et al., 2021). To the best of our knowledge, this is the first report of SPLCHbV infection in C. hederacea, which expands the natural host range of SPLCHbV.

8.
J Am Chem Soc ; 144(48): 22000-22007, 2022 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-36376019

RESUMEN

Cocaine, the archetypal tropane alkaloid from the plant genus Erythroxylum, has recently been used clinically as a topical anesthesia of the mucous membranes. Despite this, the key biosynthetic step of the requisite tropane skeleton (methylecgonone) from the identified intermediate 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid (MPOA) has remained, until this point, unknown. Herein, we identify two missing enzymes (EnCYP81AN15 and EnMT4) necessary for the biosynthesis of the tropane skeleton in cocaine by transient expression of the candidate genes in Nicotiana benthamiana. Cytochrome P450 EnCYP81AN15 was observed to selectively mediate the oxidative cyclization of S-MPOA to yield the unstable intermediate ecgonone, which was then methylated to form optically active methylecgonone by methyltransferase EnMT4 in Erythroxylum novogranatense. The establishment of this pathway corrects the long-standing (but incorrect) biosynthetic hypothesis of MPOA methylation first and oxidative cyclization second. Notably, the de novo reconstruction of cocaine was realized in N. benthamiana with the two newly identified genes, as well as four already known ones. This study not only reports a near-complete biosynthetic pathway of cocaine and provides new insights into the metabolic networks of tropane alkaloids (cocaine and hyoscyamine) in plants but also enables the heterologous synthesis of tropane alkaloids in other (micro)organisms, entailing significant implications for pharmaceutical production.


Asunto(s)
Cocaína , Vías Biosintéticas
9.
Plant Dis ; 2022 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-35285258

RESUMEN

Sweet potato is a global root crop, with a worldwide production of 91.5 million tons in 2019 (FAOSTAT, 2019). However, virus diseases cause significant yield losses and quality decline in sweet potato. Up to now, over 30 different viruses have been identified in sweet potato (Clark et al. 2012). Expanding knowledge of the host range of sweet potato viruses will provide a benefit for the understanding of virus occurrence and designing appropriate virus control measures. In August 2019, ten Calystegia hederacea and two Convolvulus arvensis (Convolvulaceae) weed plants with or without symptoms of leaf yellowing symptoms were collected from various virus disease-affected sweet potato fields in four cities (Jiaozuo, Xinxiang, Zhengzhou and Kaifeng) of Henan Province for virus detection. The leaves of these plants were harvested and pooled for total RNA extraction using a Plant Total RNA Purification Kit (GMbiolab, Taichung, Taiwan). A library for high-throughput sequencing (HTS) was constructed and sequenced using the Illumina HiSeq 2000 platform by BGI Tech (Shenzhen, China). Clean reads (n = 100,570,346), each 150 bp in length, were de novo assembled using CLC Genomics Workbench 9.5 (Qiagen, USA). The assembled contigs were analyzed against the viral reference genome database in GenBank using the BLASTN and BLASTX searches. Three contigs related to sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus, family Closteroviridae) were identified (Liu et al. 2021). In addition, a total of 20 contigs, ranging from 1,019 to 9,859 bp in length with an average depth of coverage of 1439.26, showed 74.80-87.59% nucleotide (nt) sequence identities with corresponding sequences of sweet potato latent virus (SPLV, genus Potyvirus, family Potyviridae). The sequence of the 9,859-bp contig covering nearly complete genome sequence for SPLV, was deposited in GenBank (accession no.OL625609). These results demonstrated the presence of genetically diverse isolates of SPLV in the pooled samples. To further confirm the HTS result, each of the 12 samples were tested by RT-PCR using SPLV primers (SPLV-F1: 5'-AATGCCAAGGCTACAAGGAGT-3' and SPLV-R1: 5'-CAAGTAGTGTGTGTATGTTCC-3') that targets a partial conserved region of the coat protein gene in SPLV and SPCSV primers designed based on three contigs (ctg1-F1/R1, ctg2-F1/R1, and ctg3-F1/R1) (Liu et al. 2021), respectively. As a result, four symptomless C. hederacea samples tested positive for SPLV, yielding the expected approximately 500 bp PCR fragment, and one leaf yellowing C. hederacea sample tested positive for SPCSV (Liu et al. 2021). The sequences obtained from two of the four amplicons of SPLV (MZ089700 and OM056706) showed 90.2 and 89.8% nt (100 and 99.4% amino acid) identities with the corresponding sequences of the SPLV isolate Shaanxi1 from sweet potato (HQ844148). In 2021, a further 45 C. hederacea plants collected from Shangqiu (n = 6), Xinxiang (n =30) and Pingdingshan (n = 9) cities in Henan Province, were screened by RT-PCR with SPLV-F1/R1 primers, giving an incidence of 33.33%. SPLV is an important potyvirus infecting sweet potato. SPLV is asymptomatic in most sweet potato cultivars in single infection but is able to mediate synergistic viral disease in co-infection with SPCSV (Untiveros et al. 2007). To the best of our knowledge, this is the first report of SPLV in C. hederacea. The finding reported here indicated that C. hederacea may act as a reservoir of SPLV and possible infection source for the sweet potato crop.

10.
Nat Prod Rep ; 38(9): 1634-1658, 2021 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-33533391

RESUMEN

Covering: 1917 to 2020Tropane alkaloids (TAs) are a remarkable class of plant secondary metabolites, which are characterized by an 8-azabicyclo[3.2.1]octane (nortropane) ring. Members of this class, such as hyoscyamine, scopolamine, and cocaine, are well known for their long history as poisons, hallucinogens, and anaesthetic agents. Since the structure of the tropane ring system was first elucidated in 1901, organic chemists and biochemists have been interested in how these mysterious tropane alkaloids are assembled in vitro and in vivo. However, it was only in 2020 that the complete biosynthetic route of hyoscyamine and scopolamine was clarified, and their de novo production in yeast was also achieved. The aim of this review is to present the innovative ideas and results in exploring the story of tropane alkaloid biosynthesis in plants from 1917 to 2020. This review also highlights that Robinson's classic synthesis of tropinone, which is one hundred years old, is biomimetic, and underscores the importance of total synthesis in the study of natural product biosynthesis.


Asunto(s)
Alcaloides/biosíntesis , Tropanos/metabolismo , Alcaloides/química , Productos Biológicos/metabolismo , Estructura Molecular , Tropanos/química
11.
Arch Virol ; 166(11): 3225-3228, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34519925

RESUMEN

A novel varicosa-like virus was identified in a tall morning glory (Ipomoea purpurea) plant by high-throughput sequencing and tentatively named "morning glory varicosavirus" (MGVV). The complete genome of MGVV contains two segments of negative-sense single-stranded RNA of 6409 (RNA1) and 5288 (RNA2) nucleotides. RNA1 encodes a 224.3-kDa large protein (224K), and RNA2 encodes four putative proteins of 48.6 kDa (49K), 46.4 kDa (46K), 35.7 kDa (36K), and 36.8 kDa (37K), respectively. The 224K and 49K proteins show amino acid sequence similarity to the large protein (39.4%) and the 49K protein (22.6%), respectively, of red clover-associated varicosavirus, and the 36K protein shares 19.6% amino acid sequence similarity with protein 3 of lettuce big-vein associated virus. The 46K and 37K proteins share no significant sequence similarity to known functional viral sequences. Phylogenetic analysis based on the large protein of MGVV and other rhabdoviruses showed that MGVV clustered with the varicosaviruses. These analyses indicate that MGVV is a novel member of the genus Varicosavirus in the family Rhabdoviridae.


Asunto(s)
Genoma Viral , Ipomoea/virología , Filogenia , Rhabdoviridae/genética , Enfermedades de las Plantas/virología , Proteínas Virales/genética , Secuenciación Completa del Genoma
12.
Arch Virol ; 166(7): 2037-2040, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33900471

RESUMEN

Sweet potato chlorotic stunt virus (SPCSV; genus Crinivirus, family Closteroviridae) is one of the most destructive viruses infecting sweet potatoes. In this study, we determined the complete genome sequence of an SPCSV-like isolate (CH) from Calystegia hederacea Wall. (Convolvulaceae), a weed species related to sweet potato, by combining next-generation sequencing and rapid amplification of cDNA ends. Comparisons of genome sequences and organization confirmed the classification of CH as SPCSV. However, the sequences and phylogenetic data revealed substantial genetic divergence between CH and all known SPCSV isolates. The amino acid sequence identity between the putative proteins in SPCSV-CH and the corresponding proteins in other known SPCSV isolates in each case was less than 85.0%. Phylogenetic analysis indicated that SPCSV-CH is separate from the groups of the known SPCSV isolates. Additionally, SPCSV-CH RNA1 lacks a p22 gene. A 10.1-kDa putative protein (p10) encoded by a sequence in the 5'-terminal region of RNA2 in SPCSV-CH is much larger than the corresponding protein in all known SPCSV isolates.


Asunto(s)
Calystegia/virología , Crinivirus/genética , Genoma Viral/genética , Ipomoea batatas/virología , Enfermedades de las Plantas/virología , Secuencia de Aminoácidos , China , ADN Complementario/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Filogenia , ARN Viral/genética , Proteínas Virales/genética , Secuenciación Completa del Genoma/métodos
13.
J Nat Prod ; 82(7): 1813-1819, 2019 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-31310115

RESUMEN

Eight new sulfur-bridged pyranonaphthoquinone (PNQ) dimers, naquihexcins C-J (1-8), a new PNQ monomer, naquihexcin K (10), and three known analogues (9, 11, and 12) were isolated from Streptomyces sp. KIB3133. The new structures were elucidated by interpretation of spectroscopic data. Dimer 4 was synthesized via a cascade SN2 reactions between two monomers and sodium sulfide, an approach motivated by the proposed biosynthetic pathway of dimeric pyranonaphthoquinones. Naquihexcin E (3) exhibited moderate HIV-1 inhibitory activity. Naquihexcins C (1), E (3), and I (7) showed inhibitory effects against two tumor cell lines (HL-60 and MCF-7) with IC50 values ranging from 1.4 to 16.1 µM.


Asunto(s)
Fármacos Anti-VIH/farmacología , Antineoplásicos/farmacología , Naftoquinonas/química , Piranos/química , Microbiología del Suelo , Streptomyces/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Línea Celular Tumoral , Dimerización , Ensayos de Selección de Medicamentos Antitumorales , VIH-1/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Naftoquinonas/farmacología
14.
Small ; 14(14): e1704233, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29473308

RESUMEN

Hollow nanostructures with mesoporous shells are attractive for their advantageous structure-dependent high-efficiency electrochemical catalytic performances. In this work, a novel nanostructure of Fe-doped CoP hollow triangle plate arrays (Fe-CoP HTPAs) with unique mesoporous shells is designed and synthesized through a room-temperature postsynthetic ligand exchange reaction followed by a facile phosphorization treatment. The mild postsynthetic ligand exchange reaction of the presynthesized ZIF-67 TPAs with K4 [Fe(CN)6 ] in an aqueous solution at room temperature is of critical importance in achieving the final hollow nanostructure, which results in the production of CoFe(II)-PBA HTPAs that not only determine the formation of the interior voids in the nanostructure, but also provide the doping of Fe atoms to the CoP lattice. As expected, the as-prepared mesoporous Fe-CoP HTPAs exhibit pronounced activity for water splitting owing to the advantages of abundant active reaction sites, short electron and ion pathways, and favorable hydrogen adsorption free energy (ΔGH* ). For the hydrogen and oxygen evolution reactions with the Fe-CoP HTPAs in alkaline medium, the low overpotentials of 98 and 230 mV are observed, respectively, and the required cell voltage toward overall water splitting is only as low as 1.59 V for the driving current density of 10 mA cm-2 .

15.
Mol Cancer ; 16(1): 20, 2017 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-28137278

RESUMEN

BACKGROUND: Colorectal cancer remains one of the most common malignant tumors worldwide. Colorectal cancer initiating cells (CCICs) are a small subpopulation responsible for malignant behaviors of colorectal cancer. Aberrant activation of the Wnt pathways regulates the self-renewal of CCIC. However, the underlying mechanism(s) remain poorly understood. METHODS: Via retroviral library screening, we identified Nuclear Receptor-Interacting Protein 2 (NRIP2) as a novel interactor of the Wnt pathway from enriched colorectal cancer colosphere cells. The expression levels of NRIP2 and retinoic acid-related orphan receptor ß (RORß) were further examined by FISH, qRT-PCR, IHC and Western blot. NRIP2 overexpressed and knockdown colorectal cancer cells were produced to study the role of NRIP2 in Wnt pathway. We also verified the binding between NRIP2 and RORß and investigated the effect of RORß on CCICs both in vitro and in vivo. Genechip-scanning speculated downstream target HBP1. Western blot, ChIP and luciferase reporter were carried to investigate the interaction between NRIP2, RORß, and HBP1. RESULTS: NRIP2 was significantly up-regulated in CCICs from both cell lines and primary colorectal cancer tissues. Reinforced expression of NRIP2 increased Wnt activity, while silencing of NRIP2 attenuated Wnt activity. The transcription factor RORß was a key target through which NRIP2 regulated Wnt pathway activity. RORß was a transcriptional enhancer of inhibitor HBP1 of the Wnt pathway. NRIP2 prevented RORß to bind with downstream HBP1 promoter regions and reduced the transcription of HBP1. This, in turn, attenuated the HBP1-dependent inhibition of TCF4-mediated transcription. CONCLUSIONS: NRIP2 is a novel interactor of the Wnt pathway in colorectal cancer initiating cells. interactions between NRIP2, RORß, and HBP1 mediate a new mechanism for CCIC self-renewal via the Wnt activity.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Proteínas de Unión al ADN/genética , Proteínas del Grupo de Alta Movilidad/genética , Células Madre Neoplásicas/metabolismo , Proteínas del Tejido Nervioso/genética , Miembro 2 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Proteínas Represoras/genética , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Células HT29 , Proteínas del Grupo de Alta Movilidad/metabolismo , Humanos , Ratones , Trasplante de Neoplasias , Proteínas del Tejido Nervioso/metabolismo , Miembro 2 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Represoras/metabolismo , Vía de Señalización Wnt
16.
Inorg Chem ; 56(24): 14850-14858, 2017 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-29199826

RESUMEN

Four novel three-dimensional (3D) 4d-4f heterometal-organic compounds, [LnCd2(Pbc)4(Meimdc)(H2O)]·3H2O (Ln = Eu, 1a; Tb, 1b; Sm, 1c; Dy, 1d) (HPbc = 4-(4-pyridinyl)benzoic acid; H3Meimdc = 2-methyl-1H-4,5-imidazole-dicarboxylic acid), have been successfully prepared by a hydrothermal method. All the compounds are isostructural and show three-dimensional microporous pillar-layered structures with uncoordinated carboxylate sites hung in the channels. Compound 1a possesses excellent chemical stability. The luminescent investigations show that compounds 1a, 1b, 1c, and 1d display the characteristic emission bands of Ln3+ ions. Compound 1a exhibits a good potential as a luminescent sensor material for multi-responsive Ag+, Cu2+, Zn+, Co2+, and Ni2+ cations and some organic amines. Interestingly, 1a can capture Ag+, Cu2+, Zn+, Co2+, and Ni2+ cations and shows cation-dependent colorimetric response, which indicates the potential for naked sensing.

17.
Org Biomol Chem ; 15(16): 3401-3407, 2017 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-28382349

RESUMEN

A useful enantioselective Friedel-Crafts reaction of 3,5-dimethoxylphenol with nitroolefins catalyzed by a bifunctional quinine derived thiourea catalyst 9 was developed. The Michael addition products could be obtained in good to high yields (68-92%) and with excellent enantioselectivities (89-98% ee). Such a reaction is exceptionally attractive in virtue of its simple protocol, ready availability of the starting materials, and practical applications of the products.


Asunto(s)
Alquenos/química , Floroglucinol/análogos & derivados , Quinina/química , Tiourea/química , Catálisis , Floroglucinol/química , Estereoisomerismo
18.
Plant Dis ; 101(12): 2098-2103, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30677378

RESUMEN

Sweepoviruses (a group of begomoviruses that infect plants in the family Convolvulaceae) have monopartite genomes that consist of a circular, single-stranded DNA molecule. Seventy-three complete genomic sequences of sweepoviruses were characterized from the sweet potato samples collected in China. Eight sweepovirus species, including two novel species with proposed names of Sweet potato leaf curl China virus 2 and Sweet potato leaf curl Sichuan virus 2, were identified among these samples. One species, Sweet potato leaf curl Canary virus, was first identified in China. Among the 13 identified strains of Chinese sweepoviruses, 4 were newly discovered. Sweet potato leaf curl virus had the highest frequency (53.4%) of occurrence in the sweet potato samples from China. The similarities among the 73 sweepovirus genomic sequences were between 77.6 and 100.0%. Multiple recombination events were identified, and 16 recombinant sequences were determined. Recombination was observed between different species and between different strains of the same species. Recombination breakpoints were mainly localized on the intergenic region and in three open reading frames (AC1, AV1, and AV2). This study is the first comprehensive report on the genetic diversity of sweepoviruses in China.


Asunto(s)
Begomovirus , Variación Genética , Genoma Viral , Ipomoea batatas , Begomovirus/clasificación , Begomovirus/genética , China , Genoma Viral/genética , Ipomoea batatas/virología , Filogenia , Recombinación Genética
19.
Molecules ; 22(3)2017 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-28327534

RESUMEN

Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat model was used to evaluate the anti-allergic rhinitis effect of Shenqi. The effect of Shenqi on IgE-mediated degranulation was measured using rat basophilic leukemia (RBL-2H3) cells. Primary spleen lymphocytes were isolated to investigate the anti-allergic mechanism of Shenqi by detecting the expression of transcription factors via Western blot and the level of cytokines (IL-4 and IFN-γ) via ELISA. In OVA-induced AR rat models, Shenqi relieved the allergic rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and reduced the levels of IL-4 and IgE. The results from the in vitro study certified that Shenqi inhibited mast cell degranulation. Furthermore, the results of GATA3, T-bet, p-STAT6, and SOCS1 expression and production of IFN-γ and IL-4 demonstrated that Shenqi balanced the ratio of Th1/Th2 (IFN-γ/IL-4) in OVA-stimulated spleen lymphocytes. In conclusion, these results suggest that Shenqi exhibits an obvious anti-allergic effect by suppressing the mast cell-mediated allergic response and by improving the imbalance of Th1/Th2 ratio in allergic rhinitis.


Asunto(s)
Antialérgicos/farmacología , Degranulación de la Célula/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Mastocitos/efectos de los fármacos , Mastocitos/fisiología , Balance Th1 - Th2 , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Liberación de Histamina/efectos de los fármacos , Inmunoglobulina E/inmunología , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Ratas , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo
20.
Org Biomol Chem ; 14(22): 5059-64, 2016 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-27173844

RESUMEN

Phosphine-catalyzed [4 + 2] annulation between 3-aroylcoumarins and allenones has been developed. In the presence of a dipeptide phosphine catalyst 7, dihydrocoumarin-fused dihydropyrans were prepared in high yields and with excellent enantioselectivities.


Asunto(s)
Cumarinas/química , Cetonas/química , Fosfinas/química , Piranos/química , Piranos/síntesis química , Catálisis , Técnicas de Química Sintética , Estereoisomerismo
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