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1.
PLoS Pathog ; 20(6): e1012311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38885273

RESUMO

The majority of rod-shaped and some filamentous plant viruses encode a cysteine-rich protein (CRP) that functions in viral virulence; however, the roles of these CRPs in viral infection remain largely unknown. Here, we used barley stripe mosaic virus (BSMV) as a model to investigate the essential role of its CRP in virus morphogenesis. The CRP protein γb directly interacts with BSMV coat protein (CP), the mutations either on the His-85 site in γb predicted to generate a potential CCCH motif or on the His-13 site in CP exposed to the surface of the virions abolish the zinc-binding activity and their interaction. Immunogold-labeling assays show that γb binds to the surface of rod-shaped BSMV virions in a Zn2+-dependent manner, which enhances the RNA binding activity of CP and facilitates virion assembly and stability, suggesting that the Zn2+-dependent physical association of γb with the virion is crucial for BSMV morphogenesis. Intriguingly, the tightly binding of diverse CRPs to their rod-shaped virions is a general feature employed by the members in the families Virgaviridae (excluding the genus Tobamovirus) and Benyviridae. Together, these results reveal a hitherto unknown role of CRPs in the assembly and stability of virus particles, and expand our understanding of the molecular mechanism underlying virus morphogenesis.


Assuntos
Vírion , Zinco , Zinco/metabolismo , Vírion/metabolismo , Proteínas do Capsídeo/metabolismo , Montagem de Vírus/fisiologia , Vírus de Plantas/metabolismo , Vírus de Plantas/fisiologia , Doenças das Plantas/virologia , Cisteína/metabolismo , Proteínas Virais/metabolismo , Morfogênese
2.
Crit Rev Immunol ; 44(4): 91-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505924

RESUMO

Osteoarthritis (OA) is a prevalent degenerative joint disease that is closely associated with functions of ubiquitination and immune cells, yet the mechanism remains ambiguous. This study aimed to find core ubiquitination-related genes and their correlative immune infiltration in OA using weighted gene co-expression network analysis (WGCNA). The ubiquitination-related genes, datasets GSE55235 and GSE143514 were obtained from open databases. WGCNA got used to investigate key co-expressed genes. Then, we screened differentially expressed miRNAs by "limma" package in R, and constructed mRNA-miRNA network. We conducted function enrichment analysis on the identified genes. CIBERSORT was then utilized to analyze the relevance between immune infiltration and genes. Lastly, RT-qPCR was further used to verify the prediction of bioinformatics. A sum of 144 ubiquitination-related genes in OA were acquired. Enrichment analysis indicated that obtained genes obviously involved in mTOR pathway to regulate the OA development. GRB2 and SEH1L and L-arginine synergistically regulate the mTOR signaling pathway in OA. Moreover, GRB2 and SEH1L were remarkably bound up with immune cell infiltration. Additionally, GRB2 expression was upregulated and SEH1L level was downregulated in the OA development by RT-qPCR experiment. The present study identified GRB2 and SEH1L as key ubiquitination-related genes which were involved in immune infiltration in OA patients, thereby providing new drug targets for OA.


Assuntos
MicroRNAs , Osteoartrite , Humanos , MicroRNAs/genética , RNA Mensageiro/genética , Serina-Treonina Quinases TOR , Transdução de Sinais , Osteoartrite/genética
3.
Am J Hematol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980207

RESUMO

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

4.
J Chem Phys ; 160(4)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38265088

RESUMO

The aging phenomenon is commonly observed in quantum-dot light emitting diodes (QLEDs), involving complex chemical or physical processes. Resolving the underlying mechanism of these aging issues is crucial to deliver reliable electroluminescent devices in future display applications. Here, we report a reversible positive aging phenomenon that the device brightness and efficiency significantly improve after device operation, but recover to initial states after long-time storage or mild heat treatment, which can be termed as warming-up effects. Steady and transient equivalent circuit analysis suggest that the radiative recombination current dramatically increases but electron leakage from the quantum dots (QDs) to hole transport layer becomes more accessible during the warming-up process. Further analysis discloses that the notable enhancement of device efficiency can be ascribed to the filling of shell traps in gradient alloyed QDs. This work reveals a distinct positive aging phenomenon featured with reversibility, and further guidelines would be provided to achieve stable QLED devices in real display applications.

5.
Nucleic Acids Res ; 50(15): 8580-8598, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36007892

RESUMO

Bacterial adaptation is largely shaped by horizontal gene transfer, xenogeneic silencing mediated by lineage-specific DNA bridgers (H-NS, Lsr2, MvaT and Rok), and various anti-silencing mechanisms. No xenogeneic silencing DNA bridger is known for α-proteobacteria, from which mitochondria evolved. By investigating α-proteobacterium Sinorhizobium fredii, a facultative legume microsymbiont, here we report the conserved zinc-finger bearing MucR as a novel xenogeneic silencing DNA bridger. Self-association mediated by its N-terminal domain (NTD) is required for DNA-MucR-DNA bridging complex formation, maximizing MucR stability, transcriptional silencing, and efficient symbiosis in legume nodules. Essential roles of NTD, CTD (C-terminal DNA-binding domain), or full-length MucR in symbiosis can be replaced by non-homologous NTD, CTD, or full-length protein of H-NS from γ-proteobacterium Escherichia coli, while NTD rather than CTD of Lsr2 from Gram-positive Mycobacterium tuberculosis can replace the corresponding domain of MucR in symbiosis. Chromatin immunoprecipitation sequencing reveals similar recruitment profiles of H-NS, MucR and various functional chimeric xenogeneic silencers across the multipartite genome of S. fredii, i.e. preferring AT-rich genomic islands and symbiosis plasmid with key symbiosis genes as shared targets. Collectively, the convergently evolved DNA bridger MucR predisposed α-proteobacteria to integrate AT-rich foreign DNA including symbiosis genes, horizontal transfer of which is strongly selected in nature.


Assuntos
Alphaproteobacteria , Regulação Bacteriana da Expressão Gênica , Alphaproteobacteria/genética , Proteínas de Bactérias/metabolismo , DNA , Escherichia coli/genética , Escherichia coli/metabolismo , Simbiose
6.
J Integr Plant Biol ; 66(7): 1481-1499, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38695653

RESUMO

Vicinal oxygen chelate (VOC) proteins are members of an enzyme superfamily with dioxygenase or non-dioxygenase activities. However, the biological functions of VOC proteins in plants are poorly understood. Here, we show that a VOC in Nicotiana benthamiana (NbVOC1) facilitates viral infection. NbVOC1 was significantly induced by infection by beet necrotic yellow vein virus (BNYVV). Transient overexpression of NbVOC1 or its homolog from Beta vulgaris (BvVOC1) enhanced BNYVV infection in N. benthamiana, which required the nuclear localization of VOC1. Consistent with this result, overexpressing NbVOC1 facilitated BNYVV infection, whereas, knockdown and knockout of NbVOC1 inhibited BNYVV infection in transgenic N. benthamiana plants. NbVOC1 interacts with the basic leucine zipper transcription factors bZIP17/28, which enhances their self-interaction and DNA binding to the promoters of unfolded protein response (UPR)-related genes. We propose that bZIP17/28 directly binds to the NbVOC1 promoter and induces its transcription, forming a positive feedback loop to induce the UPR and facilitating BNYVV infection. Collectively, our results demonstrate that NbVOC1 positively regulates the UPR that enhances viral infection in plants.


Assuntos
Nicotiana , Proteínas de Plantas , Resposta a Proteínas não Dobradas , Nicotiana/virologia , Nicotiana/genética , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Doenças das Plantas/virologia , Regulação da Expressão Gênica de Plantas , Regiões Promotoras Genéticas/genética , Dioxigenases/metabolismo , Dioxigenases/genética
7.
J Biol Chem ; 298(11): 102555, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36183831

RESUMO

Inhibitors targeting Bruton's tyrosine kinase (BTK) have revolutionized the treatment for various B-cell malignancies but are limited by acquired resistance after prolonged treatment as a result of mutations in BTK. Here, by a combination of structural modeling, in vitro assays, and deep phospho-tyrosine proteomics, we demonstrated that four clinically observed BTK mutations-C481F, C481Y, C481R, and L528W-inactivated BTK kinase activity both in vitro and in diffused large B-cell lymphoma (DLBCL) cells. Paradoxically, we found that DLBCL cells harboring kinase-inactive BTK exhibited intact B cell receptor (BCR) signaling, unperturbed transcription, and optimal cellular growth. Moreover, we determined that DLBCL cells with kinase-inactive BTK remained addicted to BCR signaling and were thus sensitive to targeted BTK degradation by the proteolysis-targeting chimera. By performing parallel genome-wide CRISPR-Cas9 screening in DLBCL cells with WT or kinase-inactive BTK, we discovered that DLBCL cells with kinase-inactive BTK displayed increased dependence on Toll-like receptor 9 (TLR9) for their growth and/or survival. Our study demonstrates that the kinase activity of BTK is not essential for oncogenic BCR signaling and suggests that BTK's noncatalytic function is sufficient to sustain the survival of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Tirosina Quinase da Agamaglobulinemia/genética , Tirosina Quinase da Agamaglobulinemia/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia
8.
J Chem Phys ; 158(13): 131101, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37031138

RESUMO

The operational stability is a current bottleneck facing the quantum dot light-emitting diodes (QLEDs). In particular, the device working around turn-on voltage suffers from unbalanced charge injection and heavy power loss. Here, we investigate the operational stability of red emissive CdSe QLEDs operated at different applied voltages. Compared to the rising luminance at higher voltages, the device luminance quickly decreases when loaded around the turn-on voltage, but recovers after unloading or slight heat treatment, which is termed fatigue effects of operational QLED. The electroluminescence and photoluminescence spectra before and after a period of operation at low voltages show that the abrupt decrease in device luminance derives from the reduction of quantum yield in quantum dots. Combined with transient photoluminescence and electroluminescence measurements, as well as equivalent circuit model analysis, the electron accumulation in quantum dots mainly accounts for the observed fatigue effects of a QLED during the operation around turn-on voltage. The underlying mechanisms at the low-voltage working regime will be very helpful for the industrialization of QLED.

9.
Appl Opt ; 62(6): 1475-1482, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821307

RESUMO

This study aims to discover whether temperature has an effect on axial dispersion in a photopolymer-based holographic lens. A typical coaxial holographic lens is recorded in the acrylamide polymer system. The axial dispersion spectrum is read and collected by using a supercontinuum source and spectrometer. The temperature effects on axial dispersion in a photopolymer-based holographic lens are investigated experimentally. With increasing temperature from 23°C to 70°C, the diffraction spectrum shifts, and the axial dispersion is shortened evidently. The peak wavelength of the dispersion spectrum shifts from 629.05 to 612.50 nm with an obvious blueshift of 16.55 nm. The spatial position of the peak wavelength also decreases from around 40 to 22 mm from the material surface. Simultaneously, the position sensitivity of the device reduces from 2.53 to 1.50 nm/mm. The shortening of the effective focal length and reduction of the diffraction intensity indicate that the high temperature above 40°C is a disadvantageous factor for actual use of a holographic lens-based spectral confocal measuring device. In practical application, a constant temperature is a significant means to ensure the measurement accuracy and range.

10.
Int J Mol Sci ; 24(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36614229

RESUMO

Primary congenital hypothyroidism (CH) is a common neonatal endocrine disorder characterized by elevated concentrations of thyroid stimulating hormone (TSH) and low concentrations of free thyroxine (FT4). PAX8 and NKX2-1 are important transcription factors involved in thyroid development. In this study, we detected three novel variants in PAX8 (c.149A > C and c.329G > A) and NKX2-1 (c.706A > G) by whole exome sequencing (WES) in three unrelated CH patients with variable phenotypes. The results of Western blot and immunofluorescence analysis showed that the three variants had no effect on protein expression and subcellular localization. However, the results of the electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter assay suggested that the three variants in PAX8 and NKX2-1 both affected their DNA-binding ability and reduced their transactivation capacity. Moreover, a dominant-negative effect in K236E−NKX2-1 was identified by dual-luciferase reporter assay. To sum up, our findings extend our knowledge of the current mutation spectrum of PAX8 and NKX2-1 and provide important information for diagnosing, treating, and preventing CH in these families.


Assuntos
Hipotireoidismo Congênito , Humanos , Hipotireoidismo Congênito/genética , Fatores de Transcrição Box Pareados/genética , Fator de Transcrição PAX8/genética , Mutação
11.
Water Sci Technol ; 87(1): 304-317, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640039

RESUMO

In this study, a novel peroxydisulfate (PDS) activator (CF-nZVI-JE) was prepared via in-situ loading nano zero-valent iron (nZVI) on Juncus effusus (JE) followed with wrapping a layer of cellulose film (CF). The CF-nZVI-JE had the same 3D structure as the JE, being easy to separate from aqueous solution. The loaded nZVI existed single nanoparticles with a size of 60-100 nm except chain-type agglomeration of nanoparticles due to the stabilization of JE fibers. The activation performance of the CF-nZVI-JE for PDS was evaluated with Rhodamine B (Rh B) as a representative pollutant. Under the optimal activating conditions, the degradation rate of Rh B reached 99% within 30 min in the CF-nZVI-JE/PDS system. After five cycles, the degradation rate of Rh B was still over 85%, suggesting that the CF-nZVI-JE had good reusability. More interestingly, SO4·- and ·OH radicals were simultaneously detected in the CF-nZVI-JE/PDS system, but only SO4·- existed in the JE-ZVI/PDS system, suggesting the different activation mechanism. Meanwhile, the introduction of CF not only facilitated to the mineralization of Rh B but also significantly reduced the release amount of iron ions. Hence, the CF-nZVI-JE can be employed as a promising PDS activator for the treatment of organic wastewater.


Assuntos
Ferro , Poluentes Químicos da Água , Ferro/química , Rodaminas , Águas Residuárias , Água , Poluentes Químicos da Água/química
12.
Small ; 18(6): e2106215, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35018711

RESUMO

Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Animais , Fluorescência , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete
13.
Plant Physiol ; 186(4): 2152-2168, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33871645

RESUMO

The genomic shock of whole-genome duplication (WGD) and hybridization introduces great variation into transcriptomes, for both coding and noncoding genes. An altered transcriptome provides a molecular basis for improving adaptation during the evolution of new species. The allotetraploid cotton, together with the putative diploid ancestor species compose a fine model for study the rapid gene neofunctionalization over the genome shock. Here we report on Drought-Associated Non-coding gene 1 (DAN1), a long intergenic noncoding RNA (lincRNA) that arose from the cotton progenitor A-diploid genome after hybridization and WGD events during cotton evolution. DAN1 in allotetraploid upland cotton (Gossypium hirsutum) is a drought-responsive lincRNA predominantly expressed in the nucleoplasm. Chromatin isolation by RNA purification profiling and electrophoretic mobility shift assay analysis demonstrated that GhDAN1 RNA can bind with DNA fragments containing AAAG motifs, similar to DNA binding with one zinc finger transcription factor binding sequences. The suppression of GhDAN1 mainly regulates genes with AAAG motifs in auxin-response pathways, which are associated with drought stress regulation. As a result, GhDAN1-silenced plants exhibit improved tolerance to drought stress. This phenotype resembles the drought-tolerant phenotype of the A-diploid cotton ancestor species, which has an undetectable expression of DAN1. The role of DAN1 in cotton evolution and drought tolerance regulation suggests that the genomic shock of interspecific hybridization and WGD stimulated neofunctionalization of non-coding genes during the natural evolutionary process.


Assuntos
Secas , Gossypium/genética , Poliploidia , RNA Longo não Codificante/genética , RNA de Plantas/genética , Estresse Fisiológico/genética
14.
Plant Dis ; 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35286127

RESUMO

Tobacco streak virus (TSV) is a member of the genus Ilarvirus in the family Bromoviridae (Vinodkumar et al. 2017). TSV is transmitted by thrips, seeds, pollen, and mechanical injury and has a broad host range, causing severe damage to several horticultural, oil and food crops including tobacco, sunflower, peanut, cotton, and soybean (Zambrana-Echevarría et al. 2021). TSV is now distributed mainly in the United States (McDaniel et al. 1992; Zambrana-Echevarría et al. 2021), India (Jain et al. 2008), Iran (Hosseini et al. 2012), Australia (Sharman et al. 2009) and Mexico (Silva-Rosales et al. 2013). Purple coneflower (Echinacea purpurea L.) is widely grown in China as an important herbal ornamental plant. In June 2020, Echinacea purpurea with the symptoms of necrosis lesions, malformation, and stunting were observed in the field of Haidian district, Beijing, China (40°2'69″ N, 116°28'28″ E) (Supplementary Fig. 1A). Total RNA of leaf tissue extracted using the hot borate method (Liang et al. 2020) was used for high-throughput sequencing on Illumina HiSeq X-10 platform at Biomarker Technologies (Beijing, China). Overall, 23,988,298 reads were generated. The final contigs assembled by Mega-Hit (v1.2.9) and Cap3 (Version Date: 02/10/15) were subjected to BLAST against GenBank using BLASTn and BLASTx algorithms. Of these contigs, 297 shared high nucleotide sequence similarities to the genomic sequence of broad bean wilt virus 2, while 9 contigs showed high nt sequence similarities (95-100%) to the genomic sequence of TSV. To confirm the presence of TSV, 30 randomly selected samples from Haidian district (40°2'69″ N, 116°28'28″ E) were tested by the double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) using a TSV specific monoclonal antibody (Agdia, SAR 25500/0500), where 18 samples were positive. In addition, total RNAs from 4 DAS-ELISA positive plants were extracted for TSV detection by reverse transcription-polymerase chain reactions (RT-PCR) using primer pair specific for the coat protein gene of TSV (TSV-CP-F, 5'-ATGAATACTTTGATCCAAGGTCC-3'; TSV-CP-R, 5'-TCAGTCTTGATTCACCAGAAAA-3'). The fragment with the expected size (~700 bp) was amplified in all 4 plants (Supplementary Fig. 1B) and subjected to direct Sanger sequencing. The CP gene of TSV CNB isolate was deposited in GenBank (MZ542767) and shared 100% sequence identity at the nucleotide level with the Gyp isolate infecting Ajuga reptans from Australia (JX463347.1). Furthermore, the local lesion host Chenopodium quinoa was used to purify and propagate TSV by mechanical inoculation with infected leaf sap. A pure culture of the TSV CNB isolate was obtained by single local lesion isolation after 3 serial passages on C. quinoa and back inoculated on E. purpurea seedlings. Systemic symptomology including leaf malformation was observed on E. purpurea three weeks post-inoculation (Supplementary Fig. 2A). The existence of TSV in two symptomatic leaf samples of E. purpurea was further verified by RT-PCR using specific primer pair (TSV-CP-F/R) (Supplementary Fig. 2B). In addition, the purified TSV CNB isolate was also inoculated to Nicotiana tabacum (Supplementary Fig. 2C). As previously reported (More et al. 2017), the Nicotiana tabacum plants infected with TSV developed typical streaks in systemic leaves. To the best of our knowledge, this is the first report of TSV on E. purpurea in China. This finding will assist further investigation into the epidemiology of diseases caused by TSV in China. Future studies are required to determine the incidence and impact that TSV might have on E. purpurea and other hosts in China.

15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(1): 109-115, 2022 Jan 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-35545370

RESUMO

N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications for eukaryotic mRNA. Under the catalytic regulation of relevant enzymes, m6A participates in the body's pathophysiological processes via mediating RNA transcription, splicing, translation, and decay. In the past, we mainly focused on the regulation of m6A in tumors such as hematological tumors, cervical cancer, breast cancer. In recent years, it has been found that m6A is enriched in mRNAs of neurogenesis, cell cycle, and neuron differentiation. Its regulation in the nervous system is gradually being recognized. When the level of m6A modification and the expression levels of relevant enzyme proteins are changed, it will cause neurological dysfunction and participate in the occurrence and conversion of neurological diseases. Recent studies have found that the m6A modification and its associated enzymes were involved in major depressive disorder, Parkinson's disease, Alzheimer's disease, Fragile X syndrome, amyotrophic lateral sclerosis, and traumatic brain injury, and they also play a key role in the development of neurological diseases and many other neurological diseases. This paper mainly reviewed the recent progress of m6A modification-related enzymes, focusing on the impact of m6A modification and related enzyme-mediated regulation of gene expression on the central nervous system diseases, so as to provide potential targets for the prevention of neurological diseases.


Assuntos
Transtorno Depressivo Maior , Adenosina/metabolismo , Epigênese Genética , Humanos , Metilação , RNA Mensageiro/metabolismo
16.
J Proteome Res ; 20(1): 270-278, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33118822

RESUMO

Comprehensive characterization of therapeutic monoclonal antibody (mAb) structures is critical for drug development but remains challenging due to the inherent structural heterogeneity. In this study, an integrated strategy has been developed to characterize trastuzumab structural heterogeneity, which has prominent advantages in fast sample preparation with minimal artifacts, and complementary information obtained from intact mass and middle-down analyses. Our methods were all developed on an electron transfer dissociation (ETD)-enabled Q-TOF instrument. As a result, more than 13 structurally different proteoforms were easily identified and quantified through native and denatured intact mass analysis, which may result from the collective differences in glycosylation and C-terminal lysine clipping. Based on collision-induced dissociation and ETD-combined middle-down analysis, sequence coverage values of 28, 45, and 41% for trastuzumab Fc/2, Lc, and Fd subunits, respectively, were reached in a single LC run. The main glycan structure and relative abundance level were determined, and the glycosylation site was confirmed to be on the Fc fragment Asn 61. We finally integrated the native MS and middle-down results to have a more realistic detection of molecular weight, sequence variants, and glycosylation variants of trastuzumab. Applying the integrated strategy, we successfully completed the comprehensive characterization of adalimumab and found unexpected C-terminal lysine-modified variants (dataset identifier PXD021287). Overall, our integration strategy can be easily implemented for in-depth mAb structural heterogeneity characterization during pharmaceutical development and quality control.


Assuntos
Anticorpos Monoclonais , Adalimumab , Glicosilação , Espectrometria de Massas , Trastuzumab
17.
BMC Genomics ; 22(1): 443, 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120591

RESUMO

BACKGROUND: An evolutionary model using diploid and allotetraploid cotton species identified 80 % of non-coding transcripts in allotetraploid cotton as being uniquely activated in comparison with its diploid ancestors. The function of the lncRNAs activated in allotetraploid cotton remain largely unknown. RESULTS: We employed transcriptome analysis to examine the relationship between the lncRNAs and mRNAs of protein coding genes (PCGs) in cotton leaf tissue under abiotic stresses. LncRNA expression was preferentially associated with that of the flanking PCGs. Selected highly-expressed lncRNA candidates (n = 111) were subjected to a functional screening pilot test in which virus-induced gene silencing was integrated with abiotic stress treatment. From this low-throughput screen, we obtained candidate lncRNAs relating to plant height and tolerance to drought and other abiotic stresses. CONCLUSIONS: Low-throughput screen is an effective method to find functional lncRNA for further study. LncRNAs were more active in abiotic stresses than PCG expression, especially temperature stress. LncRNA XLOC107738 may take a cis-regulatory role in response to environmental stimuli. The degree to which lncRNAs are constitutively expressed may impact expression patterns and functions on the individual gene level rather than in genome-wide aggregate.


Assuntos
Gossypium , RNA Longo não Codificante , Secas , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Filogenia , Proteínas de Plantas/genética , RNA Longo não Codificante/genética , Estresse Fisiológico/genética
18.
Sleep Breath ; 25(4): 2259-2267, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33532989

RESUMO

OBJECTIVES: Currently, mobile penetration is high amongst college students. The aims of this study were to investigate the characteristics of mobile phone use and to explore the influence of mobile phone use characteristics on sleep quality amongst college students. METHODS: From December 2016 to January 2017, we collected mobile phone use characteristics and sleep quality data using the Pittsburgh Sleep Quality Index (PSQI) and standardised questionnaires that were answered by 4500 medical university students in Liaoning Province (actual response rate of 94%, n = 4234 college students). This study used the SPSS 21.0 software to establish the database and perform the statistical analysis. RESULTS: One hundred percent of the college students had mobile phones and used mobile phones for entertainment (91%), work (51%), obtaining information (61%), and other purposes (23%). Additionally, there was a statistically significant difference in the PSQI score between students who held the phone at a distance of more than 10 cm from their eyes and those who held it a distance of less than 10 cm (P = 0.002). Multiple logistic regression analysis showed that the risk of poor sleep quality was 1.21-1.53 times higher for those who spent more than 5 h a day using their phones and 1.41-1.59 times higher for those who used their phones for more than half an hour before going to bed when the lights were off. CONCLUSIONS: Daily cumulative mobile phone use and use with the lights off before sleep are associated with poorer sleep quality.


Assuntos
Uso do Telefone Celular/estatística & dados numéricos , Escolas para Profissionais de Saúde/estatística & dados numéricos , Qualidade do Sono , Estudantes/estatística & dados numéricos , Adulto , China , Feminino , Humanos , Masculino , Universidades , Adulto Jovem
19.
Ultrason Imaging ; 43(4): 175-185, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957822

RESUMO

Portable ultrasound has been extensively used for diagnostic applications in health monitoring, emergency rooms, and ambulances. However, these handheld ultrasound systems may suffer from heat and battery issues attributed to the large power consumption of the transmitter. Additionally, the largest portion of the direct current (DC) power consumption can be attributed to the amplifier in the digital-to-analog converter (DAC) of the transmitter and to the analog-to-digital converter (ADC) of the receiver. Therefore, the number of transmit/receive channels in a portable ultrasound instrument is one of the crucial design factors regarding heat and battery related issues. To address these problems, we propose an acoustic-field beamforming (AFB) technique for low-power portable ultrasound systems with a single receive and five transmit channels. Finally, the simulation, experimental, and in vivo results verified the feasibility of this approach.


Assuntos
Acústica , Simulação por Computador , Ultrassonografia
20.
BMC Plant Biol ; 20(1): 219, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414380

RESUMO

BACKGROUND: Phased small interfering RNA (phasiRNA) is primarily derived from the 22-nt miRNA targeting loci. GhMYB2, a gene with potential roles in cotton fiber cell fate determination, is a target gene of miR828 and miR858 in the generation of phasiRNAs. RESULTS: In the presented work, through the evaluation of phasing scores and phasiRNA distribution pattern, we found that phasiRNAs from GhMYB2 were derived from the 3' cleavage fragments of 22-nt miR828 and 21-nt miR858 respectively. These two miRNA targeting sites initiated two phasing frames on transcripts of one locus. By means of RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE), we further demonstrated that phasiRNAs derived from the two phasing frames played a role in cis-regulation of GhMYB2. The phasiRNAs derived from GhMYB2 were expressed in the somatic tissues, especially in anther and hypocotyl. We further employed our previous small RNA sequencing data as well as the degradome data of cotton fiber bearing ovules, anthers, hypocotyls and embryogenic calli tissues published in public databases, to validate the expression, phasing pattern and functions of phasiRNAs. CONCLUSIONS: The presenting research provide insights of the molecular mechanism of phasiRNAs in regulation of GhMYB2 loci.


Assuntos
Regulação da Expressão Gênica de Plantas , Loci Gênicos , Gossypium/genética , Proteínas de Plantas/genética , RNA de Plantas/metabolismo , Transativadores/genética , Gossypium/metabolismo , Proteínas de Plantas/metabolismo , Transativadores/metabolismo
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