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1.
Biomol Biomed ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615341

RESUMO

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered on PROSPERO (CRD42022363229).

2.
J Orthop Surg Res ; 19(1): 172, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454504

RESUMO

PURPOSE: The clinical outcomes of patients who received a cervical collar after anterior cervical decompression and fusion were evaluated by comparison with those of patients who did not receive a cervical collar. METHODS: All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 October 2023 were included. All outcomes were analysed using Review Manager 5.4. RESULTS: Four studies with a total of 406 patients were included, and three of the studies were randomized controlled trials. Meta-analysis of the short-form 36 results revealed that wearing a cervical collar after anterior cervical decompression and fusion was more beneficial (P < 0.05). However, it is important to note that when considering the Neck Disability Index at the final follow-up visit, not wearing a cervical collar was found to be more advantageous. There were no statistically significant differences in postoperative cervical range of motion, fusion rate, or neck disability index at 6 weeks postoperatively (all P > 0.05) between the cervical collar group and the no cervical collar group. CONCLUSIONS: This systematic review and meta-analysis revealed no significant differences in the 6-week postoperative cervical range of motion, fusion rate, or neck disability index between the cervical collar group and the no cervical collar group. However, compared to patients who did not wear a cervical collar, patients who did wear a cervical collar had better scores on the short form 36. Interestingly, at the final follow-up visit, the neck disability index scores were better in the no cervical collar group than in the cervical collar group. PROSPERO registration number: CRD42023466583.


Assuntos
Doenças da Coluna Vertebral , Fusão Vertebral , Humanos , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Discotomia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Resultado do Tratamento
3.
J Integr Plant Biol ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517054

RESUMO

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.

4.
Sci Data ; 11(1): 161, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307894

RESUMO

Anisodus tanguticus is a medicinal herb that belongs to the Anisodus genus of the Solanaceae family. This endangered herb is mainly distributed in Qinghai-Tibet Plateau. In this study, we combined the Illumina short-read, Nanopore long-read and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to de novo assemble the A. tanguticus genome. A high-quality chromosomal-level genome assembly was obtained with a genome size of 1.26 Gb and a contig N50 of 25.07 Mb. Of the draft genome sequences, 97.47% were anchored to 24 pseudochromosomes with a scaffold N50 of 51.28 Mb. In addition, 842.14 Mb of transposable elements occupying 66.70% of the genome assembly were identified and 44,252 protein-coding genes were predicted. The genome assembly of A. tanguticus will provide genetic repertoire to understand the adaptation strategy of Anisodus species in the plateau, which will further promote the conservation of endangered A. tanguticus resources.


Assuntos
Genoma de Planta , Plantas Medicinais , Solanaceae , Anotação de Sequência Molecular , Filogenia , Plantas Medicinais/genética , Solanaceae/genética , Tibet , Cromossomos de Plantas
5.
Front Surg ; 11: 1284967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327546

RESUMO

Background: Adjacent segmental degeneration after lumbar fusion is one of the common long-term complications after lumbar fusion. With the continuous development of adjacent segmental degeneration, patients who fail conservative treatment often need reoperation to relieve symptoms. In recent years, the technique of bilateral microdecompression through unilateral approach under microchannel has been widely used in the treatment of lumbar degenerative diseases. However, the efficacy of this procedure for adjacent-segment degeneration after lumbar fusion has not been established. Here, we report a case of bilateral microscopic decompression via a unilateral approach through a microchannel in a patient with adjacent segmental degeneration after lumbar fusion. Case report: A 70-year-old male patient was admitted to hospital because of lumbago accompanied by left lower extremity pain, numbness and weakness for 2 years, which aggravated for 2 months. Ten years ago, he underwent PLIF for lumbar spinal stenosis, and recovered well after the operation. According to imaging data and physical examination, the diagnosis was adjacent segmental degeneration after lumbar fusion. Bilateral microdecompression was performed through a unilateral approach under a microchannel. Good clinical outcomes was observed through 1-year postoperative follow-up. Conclusions: This report reports the successful treatment of a patient with ASD 10 years after lumbar fusion. Bilateral microdecompression via a unilateral approach under a microchannel is a safe and effective method for the treatment of ASD after lumbar fusion with good surgical outcomes.

6.
Sci Rep ; 14(1): 192, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168685

RESUMO

Lumbar disc herniation (LDH) is a clinically common degenerative disease of the spine, and spinal-pelvic sagittal balance and paravertebral muscle degeneration have been a research focus in recent years. To explore the relationship between the degeneration of paravertebral muscle and the changes in the spinal-pelvic sagittal parameters in LDH patients, 105 LDH patients (experimental group) and 63 healthy volunteers (control group) hospitalized in Ordos Central Hospital from January 2020 and January 2023 were included as study subjects. All the patients underwent lumbar magnetic resonance imaging and spinal X-ray using uniform criteria. The correlation between the paravertebral muscle and sagittal-pelvic sagittal parameters of the patients with LDH was obtained from two imaging examinations, and the data were organized and grouped to explore the correlation between these parameters. No significant difference in general data existed between the groups (P > 0.05). In the L4/5 LDH patients group, the ratio of fat infiltration (FIR) in the healthy side [multifidus (MF) and erector spinae (ES)] was negatively correlated with the lumbar lordosis (LL) (r = -0.461, r = -0.486, P < 0.05). The relative cross-sectional area (RCSA) of the bilateral MF was positively correlated with the pelvic tilt (r = 0.549, r = 0.515, P < 0.05). The bilateral ES RCSA was negatively correlated with the sagittal vertical axis (r = -0.579, r = -0.621, P < 0.05). A positive correlation existed between the RCSA and thoracic kyphosis in the healthy side ES (r = 0.614, P < 0.05). In the L5/S1 LDH patients group, a negative correlation existed between the FIR and LL in the healthy side ES (r = -0.579, P < 0.05). Thus, the paravertebral muscle parameters were correlated with the spinal-pelvic sagittal parameters in the patients with LDH.


Assuntos
Deslocamento do Disco Intervertebral , Lordose , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/patologia , Lordose/patologia , Pelve/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Músculos/patologia , Estudos Retrospectivos
7.
Inorg Chem ; 63(2): 1388-1394, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38166363

RESUMO

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.

8.
Exp Ther Med ; 26(4): 479, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37745044

RESUMO

Degenerative lumbar spinal stenosis (DLSS) is a condition in which the body is held in a poor posture for a long period of time, resulting in a change in the stress structure of the lumbar spine that causes degenerative changes in the muscles of the spine. The sagittal balance of the spine and pelvis and the degeneration of the paravertebral muscles have been the focus of recent research. To explore the relationship between paraspinal muscle degeneration and changes in spine-pelvic sagittal parameters in patients with DLSS, 95 patients with DLSS (experimental group) and 70 healthy volunteers (control group) hospitalized in the Ordos Central Hospital between January 2020 and January 2022 were included as study subjects. All patients underwent lumbar magnetic resonance imaging and spinal X-ray using uniform criteria. The correlation between paravertebral muscle parameters and sagittal-pelvic sagittal parameters in patients with DLSS was obtained from two imaging examinations, and the data were organized and grouped in order to explore the correlation between these parameters. There was no significant difference in the general data between the two groups (P>0.05). In the L4-5 DLSS patient group, the ratio of fat infiltration in the right erector spinae (ES) muscle was negatively correlated with thoracic kyphosis (TK) (r=-0.536; P<0.05) but not significantly in the left side. The relative cross-sectional area of the left multifidus muscle (MF RCSA) was positively correlated with TK (r=0.685; r=0.615; P<0.05) but not significantly in the right side. In the L5-S1DLSS patient group, the right MF RCSA and right ES RCSA were significantly positively correlated with TK (r=0.685; r=0.615; P<0.05) but not significant in the left side. Thus, paravertebral muscle parameters were correlated with spinal-pelvic sagittal parameters in patients with DLSS.

9.
J Orthop Surg Res ; 18(1): 479, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400862

RESUMO

PURPOSE: The clinical outcomes of using a tubular microdiscectomy for lumbar disc herniation were evaluated by comparison with conventional microdiscectomy. METHODS: All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 May 2023 were included. All outcomes were analysed using Review Manager 5.4. RESULTS: This meta-analysis included four randomized controlled studies with a total of 523 patients. The results showed that using tubular microdiscectomy for lumbar disc herniation was more effective than conventional microdiscectomy in improving the Oswestry Disability Index (P < 0.05). However, there were no significant differences in operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate (all P > 0.05) between the tubular microdiscectomy and conventional microdiscectomy groups. CONCLUSIONS: Based on our meta-analysis, it was found that the tubular microdiscectomy group had better outcomes than the conventional microdiscectomy group in terms of Oswestry Disability Index. However, there were no significant differences between the two groups in terms of operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate. Current research suggests that tubular microdiscectomy can achieve clinical results similar to those of conventional microdiscectomy. PROSPERO registration number is: CRD42023407995.


Assuntos
Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Perda Sanguínea Cirúrgica , Vértebras Lombares/cirurgia , Microcirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Discotomia/efeitos adversos , Discotomia/métodos , Resultado do Tratamento
10.
Inorg Chem ; 62(27): 10675-10683, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37381902

RESUMO

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.

11.
Arch Virol ; 168(5): 155, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37145192

RESUMO

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.


Assuntos
Ageratum , Luteoviridae , Tombusviridae , Genoma Viral , Filogenia , Tombusviridae/genética , Luteoviridae/genética , Genômica , Nucleotídeos , China , Fases de Leitura Aberta , Doenças das Plantas , RNA Viral/genética
12.
Plant Dis ; 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165550

RESUMO

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.

13.
Proc Natl Acad Sci U S A ; 120(17): e2302448120, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37068250

RESUMO

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.


Assuntos
Cocaína , Hiosciamina , Solanaceae , Filogenia , Simulação de Acoplamento Molecular , Tropanos , Solanaceae/genética , Genômica , Metiltransferases/genética
14.
ACS Chem Biol ; 18(1): 102-111, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36623177

RESUMO

Guvermectin is a novel plant growth regulator that has been registered as a new agrochemical in China. It is an adenosine analogue with an unusual psicofuranose instead of ribose. Herein, the gene cluster responsible for guvermectin biosynthesis in Streptomyces caniferus NEAU6 is identified using gene interruption and heterologous expression experiments. A key intermediate psicofuranine 6'-phosphate (PMP) is chemically synthesized, and the functions of GvmB, C, D, and E are verified by individual stepwise enzyme reactions in vitro. The results also show that the biosynthesis of guvermectin is coupled with adenosine production by a single cluster. The higher catalytic efficiency of GvmB on PMP than AMP ensures the effective biosynthesis of guvermectin. Moreover, a phosphoribohydrolase GvmA is employed in the pathway that can hydrolyze AMP but not PMP and shows higher catalytic efficiency for the AMP hydrolysis than that of the AMP dephosphorylation by GvmB, leading to shunting of adenosine biosynthesis toward the production of guvermectin. Finally, the crystal structure of GvmE in complex with the product PMP has been solved. Glu160 at the C-terminal is identified as the acid/base for protonation/deprotonation of N7 of the adenine ring, demonstrating that GvmE is a noncanonical adenine phosphoribosyltransferase.


Assuntos
Adenina Fosforribosiltransferase , Ácido Glutâmico , Adenina Fosforribosiltransferase/química , Adenosina , Monofosfato de Adenosina/química , Modelos Moleculares
15.
J Am Chem Soc ; 144(48): 22000-22007, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36376019

RESUMO

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.


Assuntos
Cocaína , Vias Biossintéticas
16.
Nat Commun ; 13(1): 4994, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008484

RESUMO

Tropane alkaloids such as hyoscyamine and cocaine are of importance in medicinal uses. Only recently has the hyoscyamine biosynthetic machinery become complete. However, the cocaine biosynthesis pathway remains only partially elucidated. Here we characterize polyketide synthases required for generating 3-oxo-glutaric acid from malonyl-CoA in cocaine biosynthetic route. Structural analysis shows that these two polyketide synthases adopt distinctly different active site architecture to catalyze the same reaction as pyrrolidine ketide synthase in hyoscyamine biosynthesis, revealing an unusual parallel/convergent evolution of biochemical function in homologous enzymes. Further phylogenetic analysis suggests lineage-specific acquisition of polyketide synthases required for tropane alkaloid biosynthesis in Erythroxylaceae and Solanaceae species, respectively. Overall, our work elucidates not only a key unknown step in cocaine biosynthesis pathway but also, more importantly, structural and biochemical basis for independent recruitment of polyketide synthases in tropane alkaloid biosynthesis, thus broadening the understanding of conservation and innovation of biosynthetic catalysts.


Assuntos
Cocaína , Hiosciamina , Filogenia , Policetídeo Sintases/metabolismo , Tropanos/metabolismo
17.
ACS Appl Mater Interfaces ; 14(36): 41577-41587, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36043320

RESUMO

Flexible pressure sensors and aqueous batteries have been widely used in the rapid development of wearable electronics. The synergistic functionalities of versatile materials with multidimensional architectures are recognized to have a significant impact on the performance of flexible electronics. Herein, a facile hydrothermal strategy was demonstrated to conformally grow vanadium dioxide nanosheets on carbonized cotton fabrics (VO2/CCotton), which is a candidate material used in flexible piezoresistive sensors. As a result, the VO2/CCotton-based pressure sensor behaved with high sensitivity (S = 7.12 kPa-1 in the pressure range of 0-2.0 kPa) and a stable sensing ability in a wide pressure scale of 0-120 kPa. Further practical applications were performed in monitoring delicate physiological signals as well, such as twisting, blowing, and voice vibration recognitions. In addition, another application for energy storage was investigated as well. A quasi-solid-state aqueous zinc-ion battery was assembled with VO2/CCotton as the cathode and a film of Zn nanosheets/carbon nanotube as the anode. A capacity as high as 301.5 mAh g-1 and remarkable durability of 88.7% capacity retention after 5000 cycles at 10 A g-1 were found. These exceptional outcomes are attributed to the unique three-dimensional architecture and the prominent synergetic effects of CCotton and VO2 and allow for the proposal of novel guidelines for next-generation multifunctional flexible electronics.

18.
Nat Prod Bioprospect ; 12(1): 15, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426005

RESUMO

Erythroxylum P. Browne is the largest and most representative genus of Erythroxylaceae family. It contains approximately 230 species that are mainly distributed in tropical and subtropical regions. Some species in this genus, such as E. monogynum and E. coca, have been used as folk medicines in India or South America for a long history. It is well known that Erythroxylum plants are rich in tropane alkaloids, and the representative member cocaine shows remarkable activity in human central nervous system. However, many other types of active compounds have also been found in Erythroxylum along with the broadening and deepening of phytochemical research. To date, a total of 383 compounds from Erythroxylum have been reported, among which only 186 tropane alkaloids have been reviewed in 2010. In this review, we summarized all remained 197 compounds characterized from 53 Erythroxylum species from 1960 to 2021, which include diterpenes, triterpenes, alkaloids, flavonoids, and other derivates, providing a comprehensive overview of phytoconstituents profile of Erythroxylum plants. In addition, the biological activities of representative phytochemicals and crude extracts were also highlighted.

19.
Plant Dis ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35285258

RESUMO

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.

20.
Chem Commun (Camb) ; 58(20): 3322-3325, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35179528

RESUMO

Two inorganic-organic hybrid isopolyoxoniobates (1 and 2) based on new high-nuclearity {Nb54O151} clusters have been synthesized under hydrothermal conditions. In particular, the combination of the unique {Nb54O151} clusters with copper-amine complexes has led to rare helical nanotubes, which are further linked by alkali metal cations or copper-amine complexes into two 2D similar bamboo-raft-like layered networks (1 and 2), respectively. Compound 1 exhibits effective base-catalytic decomposition of chemical warfare agent simulants dimethyl methylphosphonate (DMMP) and diethyl cyanophosphonate (DECP).

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