Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
1.
Sci Adv ; 10(27): eadl6428, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959319

RESUMO

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.


Assuntos
Regulação Bacteriana da Expressão Gênica , Homeostase , Ferro , Regiões Promotoras Genéticas , Synechocystis , Ferro/metabolismo , Synechocystis/metabolismo , Synechocystis/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Cianobactérias/metabolismo , Cianobactérias/genética , Perfilação da Expressão Gênica
2.
Anal Chim Acta ; 1315: 342797, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879209

RESUMO

BACKGROUND: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance. RESULTS: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL). SIGNIFICANCE: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs.


Assuntos
Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Recombinases/metabolismo , Proliferação Nociva de Algas , Ouro/química , Proteínas Associadas a CRISPR/genética , Endodesoxirribonucleases/genética , Proteínas de Bactérias/genética
3.
Plant Physiol ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38796833

RESUMO

Recent global marine lipidomic analysis reveals a strong relationship between ocean temperature and phytoplanktonic abundance of omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential for human nutrition and primarily sourced from phytoplankton in marine food webs. In phytoplanktonic organisms, EPA may play a major role in regulating the phase transition temperature of membranes, while the function of DHA remains unexplored. In the oleaginous diatom Phaeodactylum tricornutum, DHA is distributed mainly on extraplastidial phospholipids, which is very different from the EPA enriched in thylakoid lipids. Here, CRISPR/Cas9-mediated knockout of delta-5 elongase (ptELO5a), which encodes a delta-5 elongase (ELO5) catalyzing the elongation of EPA to synthesize DHA, led to a substantial interruption of DHA synthesis in P. tricornutum. The ptELO5a mutants showed some alterations in transcriptome and glycerolipidomes, including membrane lipids and triacylglycerols under normal temperature (22°C), and were more sensitive to elevated temperature (28°C) than wild type. We conclude that PtELO5a-mediated synthesis of small amounts of DHA has indispensable functions in regulating membrane lipids, indirectly contributing to storage lipid accumulation, and maintaining thermomorphogenesis in P. tricornutum. This study also highlights the significance of DHA synthesis and lipid composition for environmental adaptation of P. tricornutum.

4.
Nat Plants ; 10(4): 618-632, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38409290

RESUMO

Effector proteins secreted by plant pathogenic fungi are important artilleries against host immunity, but there is no precedent of such effectors being explored as antifungal targets. Here we demonstrate that MoErs1, a species-specific effector protein secreted by the rice blast fungus Magnaporthe oryzae, inhibits the function of rice papain-like cysteine protease OsRD21 involved in rice immunity. Disrupting MoErs1-OsRD21 interaction effectively controls rice blast. In addition, we show that FY21001, a structure-function-based designer compound, specifically binds to and inhibits MoErs1 function. FY21001 significantly and effectively controls rice blast in field tests. Our study revealed a novel concept of targeting pathogen-specific effector proteins to prevent and manage crop diseases.


Assuntos
Proteínas Fúngicas , Oryza , Doenças das Plantas , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Interações Hospedeiro-Patógeno , Papaína/metabolismo , Ascomicetos , Magnaporthe
5.
Cell Rep Med ; 5(1): 101373, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38232699

RESUMO

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.


Assuntos
Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/genética , Síndrome de Fadiga Crônica/diagnóstico , Exercício Físico/fisiologia , Perfilação da Expressão Gênica , Transcriptoma , Monócitos
6.
Nat Commun ; 15(1): 825, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280845

RESUMO

Prime editing allows precise installation of any single base substitution and small insertions and deletions without requiring homologous recombination or double-strand DNA breaks in eukaryotic cells. However, the applications in bacteria are hindered and the underlying mechanisms that impede efficient prime editing remain enigmatic. Here, we report the determination of vital cellular factors that affect prime editing in bacteria. Genetic screening of 129 Escherichia coli transposon mutants identified sbcB, a 3'→5' DNA exonuclease, as a key genetic determinant in impeding prime editing in E. coli, combinational deletions of which with two additional 3'→5' DNA exonucleases, xseA and exoX, drastically enhanced the prime editing efficiency by up to 100-fold. Efficient prime editing in wild-type E. coli can be achieved by simultaneously inhibiting the DNA exonucleases via CRISPRi. Our results pave the way for versatile applications of prime editing for bacterial genome engineering.


Assuntos
Proteínas de Escherichia coli , Exodesoxirribonucleases , Exodesoxirribonucleases/genética , Escherichia coli/genética , Escherichia coli/metabolismo , DNA/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Quebras de DNA de Cadeia Dupla , Sistemas CRISPR-Cas/genética
7.
Nucleic Acids Res ; 52(2): 967-976, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38096062

RESUMO

Pseudomonas aeruginosa harbors sophisticated transcription factor (TF) networks to coordinately regulate cellular metabolic states for rapidly adapting to changing environments. The extraordinary capacity in fine-tuning the metabolic states enables its success in tolerance to antibiotics and evading host immune defenses. However, the linkage among transcriptional regulation, metabolic states and antibiotic tolerance in P. aeruginosa remains largely unclear. By screening the P. aeruginosa TF mutant library constructed by CRISPR/Cas12k-guided transposase, we identify that rccR (PA5438) is a major genetic determinant in aminoglycoside antibiotic tolerance, the deletion of which substantially enhances bacterial tolerance. We further reveal the inhibitory roles of RccR in pyruvate metabolism (aceE/F) and glyoxylate shunt pathway (aceA and glcB), and overexpression of aceA or glcB enhances bacterial tolerance. Moreover, we identify that 2-keto-3-deoxy-6-phosphogluconate (KDPG) is a signal molecule that directly binds to RccR. Structural analysis of the RccR/KDPG complex reveals the detailed interactions. Substitution of the key residue R152, K270 or R277 with alanine abolishes KDPG sensing by RccR and impairs bacterial growth with glycerol or glucose as the sole carbon source. Collectively, our study unveils the connection between aminoglycoside antibiotic tolerance and RccR-mediated central carbon metabolism regulation in P. aeruginosa, and elucidates the KDPG-sensing mechanism by RccR.


Assuntos
Proteínas de Bactérias , Carbono , Pseudomonas aeruginosa , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Carbono/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias/metabolismo , Redes Reguladoras de Genes
8.
ACS Synth Biol ; 13(1): 269-281, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38061052

RESUMO

CRISPR-Cas9 systems have been widely harnessed for diverse genome editing applications because of their ease of use and high efficiency. However, the large molecular sizes and strict PAM requirements of commonly used CRISPR-Cas9 systems restrict their broad applications in therapeutics. Here, we report the molecular basis and genome editing applications of a novel compact type II-A Eubacterium ventriosum CRISPR-Cas9 system (EvCas9) with 1107 residues and distinct 5'-NNGDGN-3' (where D represents A, T, or G) PAM specificity. We determine the cryo-EM structure of EvCas9 in a complex with an sgRNA and a target DNA, revealing the detailed PAM recognition and sgRNA and target DNA association mechanisms. Additionally, we demonstrate the robust genome editing capacity of EvCas9 in bacteria and human cells with superior fidelity compared to SaCas9 and SpCas9, and we engineer it to be efficient base editors by fusing a cytidine or adenosine deaminase. Collectively, our results facilitate further understanding of CRISPR-Cas9 working mechanisms and expand the compact CRISPR-Cas9 toolbox.


Assuntos
Sistemas CRISPR-Cas , Eubacterium , Edição de Genes , Humanos , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , DNA/genética
9.
Nat Commun ; 14(1): 6519, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845234

RESUMO

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization.


Assuntos
Cromatina , RNA , Humanos , Cromatina/genética , RNA/genética , Cromossomos , DNA , RNA Nuclear Pequeno , Genoma Humano/genética
10.
Ultrason Sonochem ; 100: 106583, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708743

RESUMO

In a plane acoustic field, a model involving the radial and translational motions of bubble is derived, which is used to numerically investigate the translation of two interacting spherical cavitation bubbles. For the smaller initial distance between bubble centers, we investigate the dynamics of two bubbles, and find that they could come into contact but the velocities of closing to each other are different when the equilibrium radius is different. The results show that when the wavelength of plane acoustic field is much larger than the initial distance, the bubbles are approximately pulsating in phase. Moreover, the velocity of contact process of two bubbles can be changed by adjusting the parameters of plane acoustic field. For increasing in the initial distance, the bubbles would present two translation motions: close to each other for the pulsating in phase and away from each other for the pulsating out of phase, which could be verified by calculating the secondary Bjerknes force. Meanwhile, the larger the initial distance, the smaller the secondary Bjerknes force value is. Understanding the translation of bubble is of great significance for helpful explaining formation of streamer structures in ultrasonic cavitation.

11.
Plant Physiol Biochem ; 202: 107989, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37651953

RESUMO

The plant cadmium resistance (PCR) family proteins play important roles in maintaining metal homeostasis and detoxification. However, few functional PCR genes have been well-characterized in plants. In this study, we identified and cloned 26 BnPCR genes from the rapeseed (Brassica napus) genome. They were divided into four groups (I-IV) based on their phylogenetic relationship. Yeast functional complementation experiments showed that BnPCRs can transport copper (Cu) and cadmium (Cd) in yeast. The expression levels of the BnPCRs were variable among different organs. Moreover, most of the genes were induced by Cu2+ and Cd2+ stress. Among these genes, BnPCR10.1 was highly expressed in various organs and induced by Cu2+ and Cd2+. Therefore, we studied the function of BnPCR10.1 in more detail. BnPCR10.1 was localized to the plasma membrane (PM), and expression in yeast enhanced yeast cells to export Cu and Cd. Furthermore, overexpression of BnPCR10.1 transgenic lines pro35S::BnPCR10.1;athma5 had lower concentration of Cu in roots than athma5 mutants. In addition, transgenic plants pro35S::BnPCR10.1;atpdr8 had lower concentration of Cd in shoots and roots than atpdr8 mutants. Net Cu2+ and Cd2+ efflux assay showed that there was decreased absorption of Cu2+ and Cd2+ in the transgenic Arabidopsis elongation zone of roots than in athma5 and atpdr8 mutants, respectively. These results provide new information on BnPCRs and their roles in response to heavy metals and reveal the mechanism used by BnPCR10.1 to detoxify Cu and Cd. Our findings facilitate a theoretical basis for the genetic improvement of Cu-Cd tolerance in rapeseed.


Assuntos
Arabidopsis , Brassica napus , Brassica rapa , Brassica napus/genética , Cádmio/toxicidade , Cobre/toxicidade , Saccharomyces cerevisiae/genética , Filogenia , Proteínas de Plantas/genética , Arabidopsis/genética
12.
Mol Cell ; 83(15): 2768-2780.e6, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37402371

RESUMO

Type V CRISPR-associated systems (Cas)12 family nucleases are considered to have evolved from transposon-associated TnpB, and several of these nucleases have been engineered as versatile genome editors. Despite the conserved RNA-guided DNA-cleaving functionality, these Cas12 nucleases differ markedly from the currently identified ancestor TnpB in aspects such as guide RNA origination, effector complex composition, and protospacer adjacent motif (PAM) specificity, suggesting the presence of earlier evolutionary intermediates that could be mined to develop advanced genome manipulation biotechnologies. Using evolutionary and biochemical analyses, we identify that the miniature type V-U4 nuclease (referred to as Cas12n, 400-700 amino acids) is likely the earliest evolutionary intermediate between TnpB and large type V CRISPR systems. We demonstrate that with the exception of CRISPR array emergence, CRISPR-Cas12n shares several similar characteristics with TnpB-ωRNA, including a miniature and likely monomeric nuclease for DNA targeting, origination of guide RNA from nuclease coding sequence, and generation of a small sticky end following DNA cleavage. Cas12n nucleases recognize a unique 5'-AAN PAM sequence, of which the A nucleotide at the -2 position is also required for TnpB. Moreover, we demonstrate the robust genome-editing capacity of Cas12n in bacteria and engineer a highly efficient CRISPR-Cas12n (termed Cas12Pro) with up to 80% indel efficiency in human cells. The engineered Cas12Pro enables base editing in human cells. Our results further expand the understanding regarding type V CRISPR evolutionary mechanisms and enrich the miniature CRISPR toolbox for therapeutic applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Endonucleases/genética , DNA/genética , RNA
13.
ACS Infect Dis ; 9(8): 1534-1545, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37493514

RESUMO

Microscopic examination of thick and thin blood smears stained with Giemsa dye is considered the primary diagnostic tool for the confirmation and management of suspected clinical malaria. However, detecting gametocytes is relatively insensitive, particularly in asymptomatic individuals with low-density Plasmodium infections. To complement existing diagnostic methods, a rapid and ultrasensitive point-of-care testing (POCT) platform for malaria detection is urgently needed and necessary. A platform based on recombinase polymerase amplification (RPA) followed by CRISPR/Cas12a (referred to as RPA-CRISPR/Cas12a) was developed and optimized for the determination of Plasmodium spp. parasites, particularly Plasmodium falciparum, using a fluorescence-based assay (FBDA), lateral flow test strips (LFTS), or naked eye observation (NEO). Then, the established platform was assessed with clinical malaria isolates. Under optimal conditions, the detection threshold was 1 copy/µL for the plasmid, and the limit of detection was 3.11-7.27 parasites/µL for dried blood spots. There was no cross-reactivity against blood-borne pathogens. For the accuracies of RPA-CRISPR/Cas12a, Plasmodium spp. and P. falciparum testing were 98.68 and 94.74%, respectively. The method was consistent with nested PCR results and superior to the qPCR results. RPA-CRISPR/Cas12a is a rapid, ultrasensitive, and reliable platform for malaria diagnosis. The platform requires no or minimal instrumentation for nucleic acid amplification reactions and can be read with the naked eye. Compared with similar diagnostic methods, this platform improves the reaction speed while reducing detection requirements. Therefore, this platform has the potential to become a true POCT for malaria parasites.

14.
Heliyon ; 9(6): e17023, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37389071

RESUMO

"Double circulation" is an important strategic choice under the development of the new situation. The transformation of university scientific and technological achievements and the coordinated development of regional economy are of great significance to the construction and development of the new paradigm. In this paper, DEA method is used to measure the transformation efficiency of scientific and technological achievements of universities in 31 provinces and autonomous regions (excluding Hong Kong, Macao and Taiwan), and the entropy weight-Topsis model is used to evaluate the quality of regional economic development. The comprehensive scores of the two systems are coupled and coordinated finally. It is found that the transformation efficiency of scientific and technological achievements of universities in 31 provinces and autonomous regions (excluding Hong Kong, Macao and Taiwan) is mostly DEA effective, and the transformation ability of scientific and technological achievements of universities is strong in the regions where university resources are concentrated and the economically developed regions, meanwhile there is a big gap between regions. The transformation ability of scientific and technological achievements in the central and western regions has a big room for improvement. The transformation level of scientific and technological achievements of universities in most provinces is still at a middle level of coordination with the level of regional economic development. In view of the above research conclusions, some countermeasures and suggestions are put forward in order to promote the transformation of scientific and technological achievements and regional economic development can be more coordinated.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 301: 122979, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295381

RESUMO

A facile fluorescence probe BQBH was synthesized and investigated on its spectrum property. The result showed that the BQBH had high sensitivity and selectivity for Cd2+ with lowest detection determined as 0.14 µM by fluorescence response. The 1: 1 binding ratio between BQBH and Cd2+ was determined by Job's plot, and the binding details were further confirmed by 1H NMR titration, FT-IR spectrum and HRMS analysis. The applications including on test paper, smart phone and cell image were all also investigated.


Assuntos
Cádmio , Corantes Fluorescentes , Corantes Fluorescentes/química , Cádmio/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Ressonância Magnética
16.
Micromachines (Basel) ; 14(6)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37374809

RESUMO

A thin Silicon-On-Insulator (SOI) LDMOS with ultralow Specific On-Resistance (Ron,sp) is proposed, and the physical mechanism is investigated by Sentaurus. It features a FIN gate and an extended superjunction trench gate to obtain a Bulk Electron Accumulation (BEA) effect. The BEA consists of two p-regions and two integrated back-to-back diodes, then the gate potential VGS is extended through the whole p-region. Additionally, the gate oxide Woxide is inserted between the extended superjunction trench gate and N-drift. In the on-state, the 3D electron channel is produced at the P-well by the FIN gate, and the high-density electron accumulation layer formed in the drift region surface provides an extremely low-resistance current path, which dramatically decreases the Ron,sp and eases the dependence of Ron,sp on the drift doping concentration (Ndrift). In the off-state, the two p-regions and N-drift deplete from each other through the gate oxide Woxide like the conventional SJ. Meanwhile, the Extended Drain (ED) increases the interface charge and reduces the Ron,sp. The 3D simulation results show that the BV and Ron,sp are 314 V and 1.84 mΩ∙cm-2, respectively. Consequently, the FOM is high, reaching up to 53.49 MW/cm2, which breaks through the silicon limit of the RESURF.

17.
Adv Sci (Weinh) ; 10(20): e2206744, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37171793

RESUMO

The importance of mRNA N6-methyladenosine (m6 A) modification during tumor metastasis is controversial as it plays distinct roles in different biological contexts. Moreover, how cancer cell plasticity is shaped by m6 A modification is interesting but remains uncharacterized. Here, this work shows that m6 A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is remarkably upregulated in metastatic lung adenocarcinoma (LUAD) and indicates worse prognosis of patients. Interestingly, IGF2BP3 induces partial epithelial-mesenchymal-transition (EMT) and confers LUAD cells plasticity to metastasize through m6 A-dependent overactivation of Notch signaling. Mechanistically, IGF2BP3 recognized m6 A-modified minichromosome maintenance complex component (MCM5) mRNAs to prolong stability of them, subsequently upregulating MCM5 protein, which competitively inhibits SIRT1-mediated deacetylation of Notch1 intracellular domain (NICD1), stabilizes NICD1 protein and contributes to m6 A-dependent IGF2BP3-mediated cellular plasticity. Notably, a tight correlation of the IGF2BP3/MCM5/Notch axis is evidenced in clinical LUAD specimens. Therefore, this study elucidates a critical role of m6 A modification on LUAD cell plasticity in fostering tumor metastasis via the above axis, providing potential targets for metastatic LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenosina , Proteínas de Ciclo Celular , Neoplasias Pulmonares/genética , RNA Mensageiro
18.
Nanoscale Adv ; 5(8): 2238-2243, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37056620

RESUMO

A novel Cu-assisted photoelectron-chemical etching is proposed to fabricate GaN nanowires. The functional mechanism of assisted metals, etchant concentrations, and the addition of H2O2 was investigated based on theoretical analysis and experiments. The low-cost metal-assisted etchant (CuSO4) proved more favorable than the conventional noble one (AgNO3) for the preparation of GaN nanowires in this work. The formed Ag dendrite blocked the etching when adopting the Ag-assisted etchant, while the Cu-assisted one did not. Moreover, the etchant consisting of 0.01 M CuSO4 and 5 M HF was demonstrated to realize a relatively good surface morphology and fast etching rate. In addition, the common oxidant H2O2 introduced a quasi-stable configuration between the Cu deposition and dissolution, slowing down the formation of the GaN nanowires. The proposed Cu-assisted photoelectron-chemical etching with the advantages of low cost, room temperature, and controllability could offer a new way to fabricate GaN nano-devices.

19.
Microbiol Spectr ; : e0447622, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36975799

RESUMO

Antimicrobial resistance (AMR) has posed a global threat to public health. The Staphylococcus aureus strains have especially developed AMR to practically all antimicrobial medications. There is an unmet need for rapid and accurate detection of the S. aureus AMR. In this study, we developed two versions of recombinase polymerase amplification (RPA), the fluorescent signal monitoring and lateral flow dipstick, for detecting the clinically relevant AMR genes retained by S. aureus isolates and simultaneously identifying such isolates at the species level. The sensitivity and specificity were validated with clinical samples. Our results showed that this RPA tool was able to detect antibiotic resistance for all the 54 collected S. aureus isolates with high sensitivity, specificity, and accuracy (all higher than 92%). Moreover, results of the RPA tool are 100% consistent with that of PCR. In sum, we successfully developed a rapid and accurate AMR diagnostic platform for S. aureus. The RPA might be used as an effective diagnostic test in clinical microbiology laboratories to improve the design and application of antibiotic therapy. IMPORTANCE Staphylococcus aureus is a species of Staphylococcus and belongs to Gram-positive. Meanwhile, S. aureus remains one of the most common nosocomial and community-acquired infections, causing blood flow, skin, soft tissue, and lower respiratory tract infections. The identification of the particular nuc gene and the other eight genes of drug-resistant S. aureus can reliably and quickly diagnose the illness, allowing doctors to prescribe treatment regimens sooner. The detection target in this work is a particular gene of S. aureus, and a POCT is built to simultaneously recognize S. aureus and analyze genes representing four common antibiotic families. We developed and assessed a rapid and on-site diagnostic platform for the specific and sensitive detection of S. aureus. This method allows the determination of S. aureus infection and 10 different AMR genes representing four different families of antibiotics within 40 min. It was easily adaptable in low-resource circumstances and professional-lacking circumstances. It should be supported in overcoming the continuous difficulty of drug-resistant S. aureus infections, which is a shortage of diagnostic tools that can swiftly detect infectious bacteria and numerous antibiotic resistance indicators.

20.
Int J Hypertens ; 2023: 1432727, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959846

RESUMO

Objectives: Previous studies reported that there were disparities in hypertension management among different ethnic groups, and this study aimed to systematically determine the prevalence, awareness, treatment, and control rates of hypertension in multiple Chinese ethnic groups. Methods: We searched Embase, PubMed, and Web of Science for articles up to 25 October, 2022. The pooled prevalence, awareness, treatment, and control rates of hypertension were estimated with 95% confidence intervals (CI). The heterogeneity of estimates among studies was assessed by the Cochran Q test and I 2 statistic. Meta-regression analyses were conducted to identify the factors influencing the heterogeneity of the pooled prevalence, awareness, treatment, and control rate of hypertension. Results: In total, 45 publications including 193,788 cases and 587,826 subjects were eligible for the analyses. The lowest prevalence was found in the Han group (27.0%), and the highest prevalence was in the Mongolian population (39.8%). The awareness rates ranged from 24.4% to 58.0% in the four ethnic groups. Both the highest treatment and control rates were found in the Mongolian population (50.6% and 16.0%, respectively), whereas the Yi group had the lowest control rate (8.0%). In addition, the study year, the mean age of subjects, mean body mass index of subjects, tobacco use (%), alcohol use (%), residence (urban%), and education (primary school%) had varied effects on heterogeneity. Conclusions: These findings highlight the disparities in prevalence, awareness, treatment, and control rates of hypertension in a different ethnic population of China, which could provide suggestions for making targeted prevention measures.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...