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1.
Cell ; 185(1): 204-217.e14, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34965378

RESUMO

Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.


Assuntos
Epigenoma , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Pinus/genética , Aclimatação/genética , Cromossomos de Plantas/genética , Cycadopsida/genética , Elementos de DNA Transponíveis/genética , Florestas , Redes Reguladoras de Genes , Tamanho do Genoma , Genômica/métodos , Íntrons , Magnoliopsida/genética
2.
EMBO J ; 42(6): e112647, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36740997

RESUMO

Neurogenesis in the developing and adult brain is intimately linked to remodeling of cellular metabolism. However, it is still unclear how distinct metabolic programs and energy sources govern neural stem cell (NSC) behavior and subsequent neuronal differentiation. Here, we found that adult mice lacking the mitochondrial urea metabolism enzyme, Arginase-II (Arg-II), exhibited NSC overactivation, thereby leading to accelerated NSC pool depletion and decreased hippocampal neurogenesis over time. Mechanistically, Arg-II deficiency resulted in elevated L-arginine levels and induction of a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) caused by impaired attachment of hexokinase-I to mitochondria. Notably, selective inhibition of OXPHOS ameliorated NSC overactivation and restored abnormal neurogenesis in Arg-II deficient mice. Therefore, Arg-II-mediated intracellular L-arginine homeostasis directly influences the metabolic fitness of neural stem cells that is essential to maintain neurogenesis with age.


Assuntos
Células-Tronco Neurais , Camundongos , Animais , Proliferação de Células , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Glicólise , Homeostase , Arginina/metabolismo
3.
N Engl J Med ; 388(22): 2025-2036, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37256974

RESUMO

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).


Assuntos
Fibrinolíticos , AVC Isquêmico , Tirofibana , Humanos , Aspirina/efeitos adversos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Tirofibana/efeitos adversos , Tirofibana/uso terapêutico , Resultado do Tratamento , Doenças Arteriais Cerebrais/tratamento farmacológico , Doenças Arteriais Cerebrais/etiologia
4.
PLoS Pathog ; 20(10): e1012579, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39413140

RESUMO

Recognizing the influence of pathogen diversity on infection dynamics is crucial for mitigating emerging infectious diseases. Characterising such diversity is often complex, for instance when multiple pathogen variants exist that interact differently with the environment and host. Here, we explore genotypic and phenotypic variation of Batrachochytrium salamandrivorans (Bsal), an emerging fungal pathogen that is driving declines among an increasing number of European amphibian species. For thirteen isolates, spanning most of the known temporal and geographical Bsal range in Europe, we mapped phenotypic diversity through numerous measurements that describe varying reproductive rates in vitro across a range of temperatures. Bsal isolates are revealed to have different thermal optima and tolerances, with phenotypic variation correlating with genomic diversity. Using a mechanistic niche model of the fire salamander (Salamandra salamandra) as an example, we illustrate how host steady-state body temperature and Bsal thermal range variation may influence pathogen growth through space and time across Europe. Our combined findings show how the identity of emergent pathogen variants may strongly influence when and which host populations are most at risk.

5.
Proc Natl Acad Sci U S A ; 120(14): e2218261120, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36972459

RESUMO

The ability to construct metal single-atom catalysts (SACs) asymmetrically coordinated with organic heteroatoms represents an important endeavor toward developing high-performance catalysts over symmetrically coordinated counterparts. Moreover, it is of key importance in creating supporting matrix with porous architecture for situating SACs as it greatly impacts the mass diffusion and transport of electrolyte. Herein, we report the crafting of Fe single atoms with asymmetrically coordinated nitrogen (N) and phosphorus (P) atoms scaffolded by rationally designed mesoporous carbon nanospheres (MCNs) with spoke-like nanochannels for boosting ring-opening reaction of epoxide to produce an array of pharmacologically important ß-amino alcohols. Notably, interfacial defects in MCN derived from the use of sacrificial template create abundant unpaired electrons, thereby stably anchoring N and P atoms and in turn Fe atoms on MCN. Importantly, the introduction of P atom promotes the symmetry-breaking of common four N-coordinated Fe sites, resulting in the Fe-N3P sites on MCN (denoted Fe-N3P-MCN) with an asymmetric electronic configuration and thus superior catalytic capability. As such, the Fe-N3P-MCN catalysts manifest a high catalytic activity for ring-opening reaction of epoxide (97% yield) over the Fe-N3P docked on nonporous carbon surface (91%) as well as the sole Fe-N4 SACs grounded on the same MCN support (89%). Density functional theory calculations reveal that Fe-N3P SAC lowers the activation barrier for the C-O bond cleavage and the C-N bond formation, thus accelerating the ring-opening of epoxide. Our study provides fundamental and practical insights into developing advanced catalysts in a simple and controllable manner for multistep organic reactions.

6.
Plant Cell ; 34(10): 3961-3982, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35766888

RESUMO

AP-1 and AP-2 adaptor protein (AP) complexes mediate clathrin-dependent trafficking at the trans-Golgi network (TGN) and the plasma membrane, respectively. Whereas AP-1 is required for trafficking to plasma membrane and vacuoles, AP-2 mediates endocytosis. These AP complexes consist of four subunits (adaptins): two large subunits (ß1 and γ for AP-1 and ß2 and α for AP-2), a medium subunit µ, and a small subunit σ. In general, adaptins are unique to each AP complex, with the exception of ß subunits that are shared by AP-1 and AP-2 in some invertebrates. Here, we show that the two putative Arabidopsis thaliana AP1/2ß adaptins co-assemble with both AP-1 and AP-2 subunits and regulate exocytosis and endocytosis in root cells, consistent with their dual localization at the TGN and plasma membrane. Deletion of both ß adaptins is lethal in plants. We identified a critical role of ß adaptins in pollen wall formation and reproduction, involving the regulation of membrane trafficking in the tapetum and pollen germination. In tapetal cells, ß adaptins localize almost exclusively to the TGN and mediate exocytosis of the plasma membrane transporters such as ATP-binding cassette (ABC)G9 and ABCG16. This study highlights the essential role of AP1/2ß adaptins in plants and their specialized roles in specific cell types.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Subunidades beta do Complexo de Proteínas Adaptadoras/metabolismo , Trifosfato de Adenosina/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Clatrina/genética , Clatrina/metabolismo , Exocitose/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Pólen/genética , Pólen/metabolismo , Fator de Transcrição AP-1/metabolismo
7.
Mol Biol Evol ; 40(5)2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37155936

RESUMO

Understanding the genetic basis of pest adaptive evolution and the risk of adaptation in response to climate change is essential for the development of sustainable agricultural practices. However, the genetic basis of climatic adaptation for the Asian corn borer (ACB), Ostrinia furnacalis, the main pest of corn in Asia and Oceania, is poorly understood. Here, we revealed the genomic loci underlying the climatic adaptation and evolution in ACB by integrating population genomic and environmental factors. We assembled a 471-Mb chromosome-scale reference genome of ACB and resequenced 423 individuals covering 27 representative geographic areas. We inferred that the ACB effective population size changes tracked with the global temperature and followed by a recent decline. Based on an integrated analysis of whole-genome selection scans and genome-wide genotype-environment association studies, we revealed the genetic basis of ACB adaption to diverse climates. For diapause traits, we identified a major effect association locus containing a circadian clock gene (period) by analyzing a diapause-segregating population. Moreover, our predictions indicated that the northern populations were more ecologically resilient to climate change than the southern populations. Together, our results revealed the genomic basis for ACB environmental adaptation and provided potential candidate genes for future evolutionary studies and genetic adaptation to climate change, intending to maintain the efficacy and sustainability of novel control techniques.


Assuntos
Mariposas , Zea mays , Animais , Zea mays/genética , Metagenômica , Biodiversidade , Temperatura , Mariposas/genética , Ásia
8.
Funct Integr Genomics ; 24(5): 163, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292359

RESUMO

Cellular proto-oncogene C-Fos forms the AP-1 transcription factor by dimerizing with proto-oncogene c-Jun; this factor upregulates the transcription of genes associated with different malignancies. However, its functions in pancreatic adenocarcinoma (PAAD) remain poorly understood. In this study, the c-Fos was increased in PAAD cells and tissues through bioinformatic analysis, RT-PCR, and WB. In two PAAD cell lines, PANC-1 and BxPC-3, we performed c-Fos knockdown studies using short hairpin RNA (shRNA). Functional analysis indicated that c-Fos depletion in PAAD cells inhibits cell proliferation and promotes ferroptosis. Chromatin Immunoprecipitation (ChIP) and Dual-luciferase experiments showed that c-Fos coupled to the promoter region of SLC7A11 stimulated its transcription, providing mechanistic insight into the process. Moreover, SLC7A11 blocked the decline of proliferation and ferroptosis by c-Fos knockdown in PAAD cells. Furthermore, a xenograft nude mouse model was established to study the impact of c-Fos on tumorigenesis in vivo. Depletion of c-Fos could suppress PC tumor growth and the expressions of SLC7A11, ki-67, and 4HNE, but overexpression of SLC7A11 reversed this process. In summary, our investigation has shown that c-Fos acts as a transcriptional regulator of SLC7A11, which may enhance tumour growth in pancreatic cancer by inhibiting ferroptosis. These results indicate that c-Fos might be a promising target for treating ferroptosis in PAAD.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Ferroptose , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-fos , Animais , Humanos , Masculino , Camundongos , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proto-Oncogene Mas/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo
9.
Anal Chem ; 96(35): 14265-14273, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39167707

RESUMO

Nonylphenol (NP) is an important fine chemical raw material and intermediate that is widely utilized in industry and may be distributed in aquatic ecosystems. Following its entry into the food and water cycles, it can subsequently enter the human body and potentially harm the human reproductive system. For the purpose of monitoring NP in water, it is thus essential to build a straightforward, affordable, and robust electrochemical sensor. Based on a two-step chemical modification proceeding and an electrostatic self-assembly effect, a double-modified ß-cyclodextrin functionalized multiwalled carbon nanotube sensor (HE-ß-CD-CTAC/F-MWCNTs) has been successfully constructed. It incorporates the excellent host-guest interaction ability of ß-cyclodextrin and the high chemical activity of cetyltrimethylammonium chloride (CTAC), and the carbon nanotubes have an enormous particular surface area and strong electrical conductivity. The electrochemical oxidation reaction of NP with the sensor is controlled by a surface adsorption process of equal numbers of protons and electrons. In accordance with the optimized experimental parameters, the limit of detection (LOD) for the sensor is 0.13 µM, and it responds linearly to NP in the concentration range of 1-200 µM. Meanwhile, the sensor has excellent repeatability, stability, and immunity to interference. For the detection of NP in real water samples, the sensor also showed an excellent recovery rate (92.8%-98.5%) and relative standard deviation (1.16%-3.26%).

10.
BMC Plant Biol ; 24(1): 350, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684982

RESUMO

BACKGROUND: Dactylicapnos is a climbing herbaceous vine, distributed from the Himalayas to southwestern China, and some of the species have important medicinal values. However, the chloroplast genomes of Dactylicapnos have never been investigated. In this study, chloroplast genomes of seven Dactylicapnos species covering all three sections and one informal group of Dactylicapnos were sequenced and assembled, and the detailed comparative analyses of the chloroplast genome structure were provided for the first time. RESULTS: The results showed that the chloroplast genomes of Dactylicapnos have a typical quadripartite structure with lengths from 172,344 bp to 176,370 bp, encoding a total of 133-140 genes, containing 88-94 protein-coding genes, 8 rRNAs and 37-39 tRNAs. 31 codons were identified as relative synonymous codon usage values greater than one in the chloroplast genome of Dactylicapnos genus based on 80 protein-coding genes. The results of the phylogenetic analysis showed that seven Dactylicapnos species can be divided into three main categories. Phylogenetic analysis revealed that seven species form three major clades which should be treated as three sections. CONCLUSIONS: This study provides the initial report of the chloroplast genomes of Dactylicapnos, their structural variation, comparative genomic and phylogenetic analysis for the first time. The results provide important genetic information for development of medical resources, species identification, infrageneric classification and diversification of Dactylicapnos.


Assuntos
Genoma de Cloroplastos , Filogenia , Evolução Molecular
11.
Mol Genet Genomics ; 299(1): 37, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494535

RESUMO

Identity by descent (IBD) segments, uninterrupted DNA segments derived from the same ancestral chromosomes, are widely used as indicators of relationships in genetics. A great deal of research focuses on IBD segments between related pairs, while the statistical analyses of segments in irrelevant individuals are rare. In this study, we investigated the basic informative features of IBD segments in unrelated pairs in Chinese populations from the 1000 Genome Project. A total of 5922 IBD segments in Chinese interpopulation unrelated individual pairs were detected via IBIS and the average length of IBD was 3.71 Mb in length. It was found that 17.86% of unrelated pairs shared at least one IBD segment in the Chinese cohort. Furthermore, a total of 49 chromosomal regions where IBD segments clustered in high abundance were identified, which might be sharing hotspots in the human genome. Such regions could also be observed in other ancestry populations, which implies that similar IBD backgrounds also exist. Altogether, these results demonstrated the distribution of common background IBD segments, which helps improve the accuracy in pedigree studies based on IBD analysis.


Assuntos
Povo Asiático , Genoma Humano , Humanos , Povo Asiático/genética , Genoma Humano/genética , Linhagem , Projetos de Pesquisa , China
12.
Small ; 20(27): e2311884, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38412403

RESUMO

Efficient and affordable price bifunctional electrocatalysts based on transition metal oxides for oxygen and hydrogen evolution reactions have a balanced efficiency, but it remains a significant challenge to control their activity and durability. Herein, a trace Ru (0.74 wt.%) decorated ultrathin CoOOH nanosheets (≈4 nm) supported on the surface of nickel foam (Ru/CoOOH@NF) is rationally designed via an electrochemically induced strategy to effectively drive the electrolysis of alkaline overall water splitting. The as-synthesized Ru/CoOOH@NF electrocatalysts integrate the advantages of a large number of different HER (Ru nanoclusters) and OER (CoOOH nanosheets) active sites as well as strong in-suit structure stability, thereby exhibiting exceptional catalytic activity. In particular, the ultra-low overpotential of the HER (36 mV) and the OER (264 mV) are implemented to achieve 10 mA cm-2. Experimental and theoretical calculations also reveal that Ru/CoOOH@NF possesses high intrinsic conductivity, which facilitates electron release from H2O and H-OH bond breakage and accelerates electron/mass transfer by regulating the charge distribution. This work provides a new avenue for the rational design of low-cost and high-activity bifunctional electrocatalysts for large-scale water-splitting technology and expects to help contribute to the creation of various hybrid electrocatalysts.

13.
Appl Environ Microbiol ; 90(2): e0157423, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38236018

RESUMO

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.


Assuntos
Trifosfato de Adenosina , Epsilonproteobacteria , Fosfotransferases (Aceptor do Grupo Fosfato) , Trifosfato de Adenosina/metabolismo , Temperatura , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Nucleotídeos
14.
Electrophoresis ; 45(5-6): 505-516, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38037287

RESUMO

Insertion/deletion polymorphisms (InDels) are a category of highly prevalent markers in the human genome, characterized by their distinctive attributes, including short amplicon sizes and low mutation rates, which have shown great potential in forensic applications. Multi-allelic InDel and multi-InDel markers, collectively abbreviated as MM-InDels, were developed to enhance polymorphism by the introduction of novel alleles. Nevertheless, the relatively low mutation rates of InDels, coupled with the founder effect, result in distinct allele frequency distributions among populations. The divergent characteristics of InDels in different populations also pose challenges to the establishment of universally efficient InDel multiplex assays. To enhance the system efficiency of the InDel assay and its applicability across diverse populations, 39 MM-InDels with high polymorphism in five different ancestry superpopulations were selected from the 1000 Genomes Project dataset and combined with an amelogenin gender marker to construct a multiplex assay (named MMIDplex). The combined power of discrimination and the cumulative probability of exclusion of 39 MM-InDels were 1 - 1.3 × 10-23 and 1 - 9.83 × 10-6 in the Chinese Han population, and larger than 1-10-19 and 1-10-4 in the reference populations, relatively. These results demonstrate that the MMIDplex assay has the potential to obtain sufficient power for individual identification and paternity test in global populations.


Assuntos
Genética Forense , Polimorfismo Genético , Humanos , Genética Forense/métodos , Frequência do Gene/genética , Povo Asiático , Mutação INDEL , Genética Populacional , China
15.
Anal Biochem ; 686: 115422, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38070664

RESUMO

Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 × 10-13 M for chlorpyrifos and 7.6 × 10-15 M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.


Assuntos
Técnicas Biossensoriais , Inseticidas , Metil Paration , Nanocompostos , Praguicidas , Óxido de Zinco , Compostos Organofosforados , Nitrogênio , Acetilcolinesterase/química , Técnicas Biossensoriais/métodos
16.
Biotechnol Bioeng ; 121(7): 2133-2146, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634289

RESUMO

L-cysteine is an important sulfur-containing amino acid being difficult to produce by microbial fermentation. Due to the lack of high-throughput screening methods, existing genetically engineered bacteria have been developed by simply optimizing the expression of L-cysteine-related genes one by one. To overcome this limitation, in this study, a biosensor-based approach for multilevel biosynthetic pathway optimization of L-cysteine from the DecR regulator variant of Escherichia coli was applied. Through protein engineering, we obtained the DecRN29Y/C81E/M90Q/M99E variant-based biosensor with improved specificity and an 8.71-fold increase in dynamic range. Using the developed biosensor, we performed high-throughput screening of the constructed promoter and RBS combination library, and successfully obtained the optimized strain, which resulted in a 6.29-fold increase in L-cysteine production. Molecular dynamics (MD) simulations and electrophoretic mobility shift analysis (EMSA) showed that the N29Y/C81E/M90Q/M99E variant had enhanced induction activity. This enhancement may be due to the increased binding of the variant to DNA in the presence of L-cysteine, which enhances transcriptional activation. Overall, our biosensor-based strategy provides a promising approach for optimizing biosynthetic pathways at multiple levels. The successful implementation of this strategy demonstrates its potential for screening improved recombinant strains.


Assuntos
Técnicas Biossensoriais , Cisteína , Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Cisteína/metabolismo , Cisteína/genética , Cisteína/biossíntese , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Engenharia Metabólica/métodos , Engenharia de Proteínas/métodos , Vias Biossintéticas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Fish Shellfish Immunol ; 145: 109354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171431

RESUMO

MicroRNAs (miRNAs) are small non-coding RNA molecules that modulate target-genes expression and play crucial roles in post-transcriptional regulation and immune system regulation. The Hong Kong oyster (Crassostrea hongkongesis), as the main marine aquaculture shellfish in the South China Sea, not only has high economic and ecological value, but also is an ideal model for conducting research on pathogen host interaction. Vibrio harveyi, a Gram negative luminescent marine bacterium, is widely distributed in coastal water environments and can cause large-scale death of C. hongkongesis. However, little in formation is available on the immune regulatory mechanisms of C. hongkongesis infected with V. harveyi. Therefore, we performed microRNA transcriptome analysis for elucidating the immunoregulation mechanism of C. hongkongesis infected with V. harveyi. The results show that a total of 308468208 clean reads and 288371159 clean tags were obtained. 222 differentially expressed miRNAs were identified. A total of 388 target genes that were differentially expressed and negatively correlated with miRNA expression were predicted by 222 DEmiRs. GO enrichment analysis of 388 DETGs showed that they were mainly enriched in the immune-related term of membrane-bounded vesicle, endocytic vesicle lumen, antigen processing and presentation of exogenous peptide antigen via MHC class I, antigen processing and presentation of peptide antigen via MHC class I, and other immune-related term. KEGG enrichment analysis showed that DETGs were mainly enriched in the Complement and coagulation cascades, Herpes simplex virus 1 infection, Bacterial invasion of epithelial cells, Antigen processing and presentation and NOD-like receptor signaling pathway. The 16 key DEmiRs and their target genes form a regulatory network for seven immune-related pathways. These results suggest that V. harveyi infection induces a complex miRNA response with wide-ranging effects on immune gene expression in the C. hongkongesis. This study explored the immune response of C. hongkongesis to V. harveyi infection at the level of miRNAs, which provides new ideas for the healthy culture and selective breeding of C. hongkongesis.


Assuntos
Crassostrea , MicroRNAs , Vibrioses , Vibrio , Animais , MicroRNAs/genética , Transcriptoma , Crassostrea/genética , Vibrio/fisiologia , Perfilação da Expressão Gênica , Peptídeos/genética
18.
J Math Biol ; 88(3): 38, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436782

RESUMO

In this paper, we study a time-delayed nonlocal reaction-diffusion model of within-host viral infections. We introduce the basic reproduction number R 0 and show that the infection-free steady state is globally asymptotically stable when R 0 ≤ 1 , while the disease is uniformly persistent when R 0 > 1 . In the case where all coefficients and reaction terms are spatially homogeneous, we obtain an explicit formula of R 0 and the global attractivity of the positive constant steady state. Numerically, we illustrate the analytical results, conduct sensitivity analysis, and investigate the impact of drugs on curtailing the spread of the viruses.


Assuntos
Viroses , Humanos , Número Básico de Reprodução , Difusão
19.
Skin Res Technol ; 30(6): e13769, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887837

RESUMO

BACKGROUND: The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV). MATERIALS AND METHODS: The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up. RESULTS: The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements. CONCLUSION: The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.


Assuntos
Glucosídeos , Paeonia , Terapia Ultravioleta , Vitiligo , Humanos , Vitiligo/terapia , Vitiligo/radioterapia , Vitiligo/tratamento farmacológico , Feminino , Masculino , Adulto , Terapia Ultravioleta/métodos , Estudos Retrospectivos , Paeonia/química , Glucosídeos/administração & dosagem , Glucosídeos/uso terapêutico , Terapia Combinada/métodos , Pessoa de Meia-Idade , Adulto Jovem , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Resultado do Tratamento , Administração Oral , Extratos Vegetais/administração & dosagem , Adolescente , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação
20.
Nucleic Acids Res ; 50(D1): D758-D764, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34614159

RESUMO

With their photosynthetic ability and established genetic modification systems, cyanobacteria are essential for fundamental and biotechnological research. Till now, hundreds of cyanobacterial genomes have been sequenced, and transcriptomic analysis has been frequently applied in the functional genomics of cyanobacteria. However, the massive omics data have not been extensively mined and integrated. Here, we describe CyanoOmicsDB (http://www.cyanoomics.cn/), a database aiming to provide comprehensive functional information for each cyanobacterial gene. CyanoOmicsDB consists of 8 335 261 entries of cyanobacterial genes from 928 genomes. It provides multiple gene identifiers, visualized genomic location, and DNA sequences for each gene entry. For protein-encoding genes, CyanoOmicsDB can provide predicted gene function, amino acid sequences, homologs, protein-domain super-families, and accession numbers for various public protein function databases. CyanoOmicsDB integrates both transcriptional and translational profiles of Synechocystis sp. PCC 6803 under various environmental culture coditions and genetic backgrounds. Moreover, CyanoOmicsDB includes 23 689 gene transcriptional start sites, 94 644 identified peptides, and 16 778 post-translation modification sites obtained from transcriptomes or proteomes of several model cyanobacteria. Compared with other existing cyanobacterial databases, CyanoOmicsDB comprises more datasets and more comprehensive functional information. CyanoOmicsDB will provide researchers in this field with a convenient way to retrieve functional information on cyanobacterial genes.


Assuntos
Proteínas de Bactérias/genética , Cianobactérias/genética , Bases de Dados Genéticas , Genoma Bacteriano , Software , Synechocystis/genética , Proteínas de Bactérias/classificação , Proteínas de Bactérias/metabolismo , Cianobactérias/classificação , Cianobactérias/metabolismo , Mineração de Dados , Perfilação da Expressão Gênica , Genômica/métodos , Internet , Fotossíntese/genética , Proteômica/métodos , Synechocystis/metabolismo , Transcriptoma
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