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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554671

RESUMO

Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. RTV is mainly metabolized by cytochrome P450 3A4 (CYP3A4) in the liver. HNF4A antisense RNA 1 (HNF4A-AS1) and HNF1A antisense RNA 1 (HNF1A-AS1) are long noncoding RNAs (lncRNAs) that regulate the expression of pregnane X receptor (PXR) and CYP3A4. This study investigated the role and molecular mechanisms of HNF4A-AS1 and HNF1A-AS1 in RTV-induced hepatotoxicity. Small hairpin RNAs were used to knock down HNF4A-AS1 and HNF1A-AS1 in Huh7 and HepG2 cells. Lactate dehydrogenase and reactive oxygen species assays were performed to assess RTV-induced hepatotoxicity. Chromatin immunoprecipitation qPCR was used to detect PXR enrichment and histone modifications in the CYP3A4 promoter. HNF4A-AS1 knockdown increased PXR and CYP3A4 expression and exacerbated RTV-induced cytotoxicity, whereas HNF1A-AS1 knockdown generated the opposite phenotype. Mechanistically, enrichment of PXR and trimethylation of histone 3 lysine 4 (H3K4me3) in the CYP3A4 promoter was increased, and trimethylation of histone 3 lysine 27 (H3K27me3) was decreased after HNF4A-AS1 knockdown. However, PXR and H3K4me3 enrichment decreased after HNF1A-AS1 knockdown. Alterations in RTV-induced hepatotoxicity caused by decreasing HNF4A-AS1 or HNF1A-AS1 were reversed by knockdown or overexpression of PXR. Increased susceptibility to RTV-induced liver injury caused by the PXR activator rifampicin was attenuated by HNF4A-AS1 overexpression or HNF1A-AS1 knockdown. Taken together, these results revealed that HNF4A-AS1 and HNF1A-AS1 modulated RTV-induced hepatotoxicity by regulating CYP3A4 expression, primarily by affecting the binding of PXR and histone modification status in the CYP3A4 promoter.

2.
ACS Macro Lett ; 11(1): 26-32, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35574802

RESUMO

Here, we report a distinct approach for regulating the substrate specificity of enzymes immobilized in microgels by a phase transition in polymer networks. The finding is demonstrated on glucose oxidase that is immobilized in thermoresponsive poly(N-isopropylacrylamide)-based microgels. Laser light scattering and enzymatic oxidation tests indicate that the broadened specificity appears at low temperatures, at which the gel matrix is in the relatively swollen state relative to its state at microgel synthesis temperature; upon heating to the relative higher temperatures, the gel matrix is not able to shrink further that offers a tight space in which the enzyme resides to retain high glucose specificity. It is proposed that polymer phase transition in the gel matrix mainly alter protein gates that control passage of substrates into active sites, making them open or close to a certain extent that enable reversible regulating the substrate specificity. The finding is also observed on bulk gels under a rational design, making it of potential interest in enzymatic biofuel cell applications.

3.
Ying Yong Sheng Tai Xue Bao ; 33(4): 1109-1117, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543066

RESUMO

In order to understand the effects of lucerne cropping rotation on the bacterial community of loess soil, a long-term field experiment was conducted in rain-fed agricultural area of Loess Plateau. The cropping systems included continuous lucerne (Medicago sativa, LC), lucerne removed and rotated with spring wheat (Triticum aestivum, LFW), lucerne removed and rotated with corn (Zea mays, LFC), lucerne removed and rotated with potato (Solanum tuberosum, LP), and lucerne removed and rotated with continuous millet (Panicum miliaceum, LM). Based on 16S rRNA high-throughput sequencing technology, we investigated soil bacterial community structure and diversity in different cropping systems, and predicted ecological function using PICRUSt method. The results showed that the dominant phyla of loess soil bacteria were Actinomycetes (20.3%-32.0%), Proteobacteria (19.2%-23.0%), Acidobacteria (12.4%-14.2%) and Chloroflexus (11.0%-12.7%). The dominant genus was Bacillus (1.9%) in lucerne-corn system and Pseudarthrobacter (2.5%) in other treatments. Rotation with annual crops decreased the relative abundance of Actinobacteria and increased that of Chloroflexi and Firmicutes. Redundancy analysis showed that the main soil factors driving soil bacterial community structure were nitrate, ammonium, and total nitrogen. PICRUSt function prediction results showed that metabolism (78.6%-79.1%) was the main function of soil bacterial communities in loess soil. Rotation with continued annual crops significantly decreased the abundance of soil bacterial carbohydrate metabolism functional genes, and significantly increased the abundance of functional genes for soil bacterial cofactors and vitamin metabolism, neurodegenerative diseases, and immune system. In conclusion, lucerne removed and rotated with continuous annual crops changed soil bacterial community structure and ecological functions. This study provided theoretical reference to explore succession characteristics of soil bacteria and to select succeeding crops for alfalfa in loess soil.


Assuntos
Actinobacteria , Solo , Actinobacteria/genética , Bactérias/genética , China , Produção Agrícola , Produtos Agrícolas , Medicago sativa , RNA Ribossômico 16S/genética , Microbiologia do Solo , Triticum/genética , Zea mays/genética
4.
Sci Total Environ ; : 155817, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561930

RESUMO

Carbonaceous aerosols (CAs) are major components of fine particulate matter (PM2.5) that dramatically influence the energy budget of Earth. However, accurate assessment of the climatic impacts of CAs is still challenging due to the large uncertainties remaining in the measurement of their optical properties. In this respect, a modified versatile aerosol concentration enrichment system integrated into optical instruments (VACES-OPTS) was set up to increase particle concentration and amplify signal-noise ratio during optical measurement. Based on the novel technique, this study was able to lower the detection limit of CAs by an order of magnitude under high temporal resolution (2 h) and small sampling flow (6 L min-1). Besides, stable and reliable optical data were obtained for absorption apportionment and source identification of black carbon (BC) and brown carbon (BrC). In the field application of the new system, high absorption coefficient of CAs in Shanghai, China was witnessed. Further analysis of the contribution of black carbon BC and BrC to light absorption revealed that BrC could account for over 15% of the total absorption at 370 nm. According to the potential source contribution function model (PSCF) classification, CAs with strong light absorption in urban Shanghai originated not only from highly polluted inland China but also from active marine ship emissions.

5.
Plant Physiol ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522008

RESUMO

Conjugation of the small ubiquitin-like modifier (SUMO) peptide to target proteins is an important post-translational modification. SAP AND MIZ1 DOMAIN- CONTAINING LIGASE1 (MdSIZ1) is an apple (Malus domestica Borkh.) SUMO E3 ligase that mediates sumoylation of its targets during plant growth and development under adverse environmental conditions. However, it is unclear how MdSIZ1 senses the various environmental signals and whether sumoylation is regulated at the transcriptional level. In this study, we analyzed the MdSIZ1 promoter and found that it contained an MBS (MYB Binding Site) motif that was essential for the response of MdSIZ1 to low temperature and drought. Subsequently, we used yeast one-hybridization screening to demonstrate that a MYB transcription factor, MdMYB2, directly bound to the MBS motif in the MdSIZ1 promoter. Phenotypic characterization of MdMYB2 and MdSIZ1 suggested that the expression of both MdMYB2 and MdSIZ1 substantially improved cold tolerance in plants. MdMYB2 was induced by low temperature and further activated the expression of MdSIZ1, thereby promoting the sumoylation of MdMYB1, a key regulator of anthocyanin biosynthesis in apple. MdMYB2 promoted anthocyanin accumulation in apple fruits, apple calli, and Arabidopsis (Arabidopsis thaliana) in an MdSIZ1-dependent manner. In addition, the interaction of MdMYB2 and the MdSIZ1 promoter substantially improved plant tolerance to cold stress. Taken together, our findings reveal an important role for transcriptional regulation of sumoylation and provide insights into plant anthocyanin biosynthesis regulation mechanisms and stress response.

6.
Plant Direct ; 6(5): e393, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35600998

RESUMO

Efficient acquisition and use of available phosphorus from the soil is crucial for plant growth, development, and yield. With an ever-increasing acreage of croplands with suboptimal available soil phosphorus, genetic improvement of sorghum germplasm for enhanced phosphorus acquisition from soil is crucial to increasing agricultural output and reducing inputs, while confronted with a growing world population and uncertain climate. Sorghum bicolor is a globally important commodity for food, fodder, and forage. Known for robust tolerance to heat, drought, and other abiotic stresses, its capacity for optimal phosphorus use efficiency (PUE) is still being investigated for optimized root system architectures (RSA). Whilst a few RSA-influencing genes have been identified in sorghum and other grasses, the epigenetic impact on expression and tissue-specific activation of candidate PUE genes remains elusive. Here, we present transcriptomic, epigenetic, and regulatory network profiling of RSA modulation in the BTx623 sorghum background in response to limiting phosphorus (LP) conditions. We show that during LP, sorghum RSA is remodeled to increase root length and surface area, likely enhancing its ability to acquire P. Global DNA 5-methylcytosine and H3K4 and H3K27 trimethylation levels decrease in response to LP, while H3K4me3 peaks and DNA hypomethylated regions contain recognition motifs of numerous developmental and nutrient responsive transcription factors that display disparate expression patterns between different root tissues (primary root apex, elongation zone, and lateral root apex).

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 278: 121328, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35537262

RESUMO

Thermally activated delayed fluorescence (TADF) molecules with aggregation-induced emission (AIE) properties have attracted great attention in recent studies. In this study, three isomeric emitters DPAC-4PYPM, DPAC-TRZ and DPAC-6PYPM with TADF are studied in toluene and crystal with the combination of polarizable continuum model (PCM) and quantum mechanics and molecular mechanics (QM/MM) method. Results show that tiny difference of intramolecular interaction is induced due to the variation in the acceptor group, thus similar geometries and stacking patterns in crystal are obtained for three molecules. Our calculation also indicates that the energy diagram is quite different for three molecules in both toluene and crystal state, while the participation of higher triplet excited states provide additional decay channels for the reverse intersystem crossing (RISC) process, which favors the generation of TADF. In addition, the bending vibrations of the phenyl in the donor and the stretching vibrations of the C=C and C-H bonds are suppressed due to the intermolecular interactions in crystal state, thus block the excited-state energy consumption pathway. It indicates that all three molecules are typical AIE systems. Our calculation results agree with experimental measurements and provide more useful information for TADF emitters with AIE properties.

8.
Gene ; 832: 146558, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35569773

RESUMO

Amino acid permeases (AAPs) play important roles in plant amino acid transport and nitrogen metabolism. In this study, we carried a comprehensive analysis for apple genes encoding AAPs using bioinformatics and molecular biology. Eleven MdAAPs were identified by a genome-wide search and comparative genomic analysis revealed relatively conserved gene composition, transmembrane characteristics, and protein structures. Phylogenetic tree construction and analysis of the conserved motifs of MdAAPs and AtAAPs showed that AAPs can be classified into three groups (I, II, and III). We compared the promoters of the identified genes and did gene functional annotation and qRT-PCR and found a relationship between apple AAPs and nitrogen deficiency. The expression profile data implied that MdAAPs exhibit diversified distributions and functions in different tissues.

9.
BMC Musculoskelet Disord ; 23(1): 417, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509097

RESUMO

BACKGROUND: This study aimed to investigate the prevalence of preoperative deep venous thrombosis (DVT) following intertrochanteric fractures in the elderly and identify the associated factors, based on which a risk prediction model was developed. METHOD: This was a retrospective single-center study of elderly patients presenting with intertrochanteric fractures between our institution between January 2017 and December 2020. Patients' duplex ultrasound (DUS) or venography results were retrieved to evaluate whether they had a preoperative deep venous thrombosis (DVT) of bilateral extremities, whereby patients were dichotomized. Various variables of interest on demographics, comorbidities, injury and biomarkers were extracted and their relationship between DVT were investigated. Statistically significant variables tested in multivariate logistics regression analyses were used to develop a risk prediction model. RESULTS: There were 855 patients eligible to be included in this study, and 105 were found to have preoperative DVT, with a prevalence rate of 12.3%. Ten factors were tested as significantly different and 2 marginally significant between DVT and non-DVT groups in the univariate analyses, but only 6 demonstrated the independent effect on DVT occurrence, including history of a VTE event (OR, 4.43; 95%CI, 2.04 to 9.62), time from injury to DVT screening (OR, 1.19; 95%CI, 1.13 to 1.25), BMI (OR, 1.11; 95%CI, 1.04-1.18), peripheral vascular disease (OR, 2.66; 95%CI, 1.10 to 6.40), reduced albumin (2.35; 95%CI, 1.48 to 3.71) and D-Dimer > 1.0 mg/L(OR, 1.90; 95%CI, 1.13 to 3.20). The DVT risk model showed an AUC of 0.780 (95%CI, 0.731 to 0.829), with a sensitivity of 0.667 and a specificity of 0.777. CONCLUSION: Despite without a so high prevalence rate of DVT in a general population with intertrochanteric fracture, particular attention should be paid to those involved in the associated risk factors above. The risk prediction model exhibited the improved specificity, but its validity required further studies to verify.


Assuntos
Fraturas do Quadril , Trombose Venosa , Idoso , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Incidência , Prevalência , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia
10.
J Exp Bot ; 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526197

RESUMO

Plants have evolved complex mechanisms to cope with fluctuating environmental nitrogen availability. However, potential genes modulating plant response to nitrate have yet to be characterized. Here, a poplar GATA transcription factor gene PdGNC was found to be greatly induced by low nitrate. Overexpressing PdGNC in poplar clone 717-1B4 (P. tremula x alba) significantly improved nitrate uptake, remobilization, and assimilation with higher nitrogen-use efficiency (NUE) and faster growth, particularly in a low nitrate condition. Conversely, CRISPR/Cas9-mediated poplar mutant gnc exhibited decreased nitrate uptake, relocation, and assimilation with lower NUE and slower growth. Assays with yeast one-hybrid, electrophoretic mobility shift, and a dual-luciferase reporter showed that PdGNC directly activated the promoters of nitrogen use pathway genes PdNRT2.4b, PdNR, PdNiR, and PdGS2, leading to a significant increase in nitrate utilization in poplar. Expectedly, the enhanced NUE promoted the growth under low nitrate availability. Taken together, PdGNC plays an important role in regulation of NUE and growth by improving nitrate acquisition, remobilization, and assimilation in poplar, and our research provides a promising strategy for tree molecular breeding to improve productivity under nitrogen limitation.

11.
Nat Neurosci ; 25(4): 515-529, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35361973

RESUMO

Prefrontal cortex (PFC) is the cognitive center that integrates and regulates global brain activity. However, the whole-brain organization of PFC axon projections remains poorly understood. Using single-neuron reconstruction of 6,357 mouse PFC projection neurons, we identified 64 projectome-defined subtypes. Each of four previously known major cortico-cortical subnetworks was targeted by a distinct group of PFC subtypes defined by their first-order axon collaterals. Further analysis unraveled topographic rules of soma distribution within PFC, first-order collateral branch point-dependent target selection and terminal arbor distribution-dependent target subdivision. Furthermore, we obtained a high-precision hierarchical map within PFC and three distinct functionally related PFC modules, each enriched with internal recurrent connectivity. Finally, we showed that each transcriptome subtype corresponds to multiple projectome subtypes found in different PFC subregions. Thus, whole-brain single-neuron projectome analysis reveals organization principles of axon projections within and outside PFC and provides the essential basis for elucidating neuronal connectivity underlying diverse PFC functions.


Assuntos
Neurônios , Córtex Pré-Frontal , Animais , Axônios , Encéfalo , Interneurônios , Camundongos , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia
12.
Front Plant Sci ; 13: 812988, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432436

RESUMO

A total of 60 WRKY family genes of ramie were identified in the ramie. The genes were unevenly distributed across 14 chromosomes in the specie and highly concentrated (72%) in the distal telomeric region. Phylogenetic analysis placed these genes into seven distinct subfamilies groups: I, II (a, b, c, d, e), and III, with group IIc containing only the variant of heptapetide sequence (WRKYGKK). Segmental duplication events (41.7%) was found to be the main driver of BnGWRKY evolution. Thirty eight from among the genes showed collinear relationships with WRKY genes from Arabidopsis thaliana, Cannabis sativa, Oryza sativa, and Zea mays. The number and density of stress and hormone responsives cis-acting elements were comparably higher than other elements, with abundant ARE and rare LTR cis-acting elements indicating the long-standing adaptability of ramie to its natural environment. GO and KEGG enrichment analysis of the WRKY target genes revealed their involvement in response to stimuli, immune system processes, transporter protein activity and antioxidant activity. Expression analysis show that most WRKYs were activated by the cadmium stress, more especially the BnGWRKY2, BnGWRKY15, BnGWRKY20, BnGWRKY50 and BnGWRKY58. Combining transcriptome, orthologous gene relationships and qPCR result, we established the possible involvement of BnGWRKY50 and BnGWRKY58 in crosstalk mechanism between secondary cell wall thickening and Cd2+ stress. This provided information into the role of BnGWRKY proteins in ramie secondary wall development and cadmium stress response to, and could serve as basis for improvement of the ramie.

13.
Biochem Pharmacol ; 201: 115057, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35489393

RESUMO

KRAS mutation and NF-κB both play crucial role in pancreatic cancer; in addition, defensin, the peptide mediator in innate immunity, can inhibit NF-κB. Assuming a strategy that targets both NF-κB and concomitantly the mutated KRAS indirectly via intensive macropinocytosis, we designed and generated a recombinant protein DF2-HSA which consists of two molecules of human beta-defensin 2 (HBD2) and a moiety of human serum albumin (HSA). As shown, the recombinant protein DF2-HSA markedly down-regulated NF-κB in both KRAS mutant MIA PaCa-2 cells and wild type BxPC-3 cells. Determined by confocal microscopy, the uptake of DF2-HSA in MIA PaCa-2 cells was more intense than that in BxPC-3 cells. The uptake was blocked by the specific inhibitor EIPA, indicating that DF2-HSA internalized via macropinocytosis. DF2-HSA displayed more potent cytotoxicity to cancer cells than HBD2. DF2-HSA induced apoptosis in cancer cells. Notably, DF2-HSA inhibited tumor cell spheroid formation, an effect comparable to that of salinomycin. DF2-HSA inhibited tumor cell migration and invasion. As detected with scanning electron microscopy, DF2-HSA strongly depleted filopodia on cell surface; and salinomycin induced similar changes. By in vivo imaging, DF2-HSA displayed intense tumor-site accumulation and lasting retention for over 14 days; however, HBD2 showed much less tumor-site accumulation and a shorter retention time for only 24 h. DF2-HSA suppressed the growth of pancreatic cancer MIA PaCa-2 xenograft in athymic mice; and its combination with gemcitabine achieved higher antitumor efficacy. In summary, the recombinant defensin/HSA fusion protein that inhibits NF-κb associated with intensive macropinocytosis is highly effective against pancreatic cancer.

14.
Genes (Basel) ; 13(4)2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35456366

RESUMO

The genus Malus is rich in species and many of its plastid genomes have been released. However, limited resources and few markers are not conducive to the comparison of differences among species and resource identification and evaluation. In this study, the complete chloroplast genome of Malus zhaojiaoensis was studied by NGS sequencing, with a total length of 159998 bp. It consists of four regions, LSC (88,070 bp), IRB (26,359 bp), SSC (19,210 bp) and IRA (26,359 bp). M. zhaojiaoensis cp genome contained a total of 111 genes made up of three classes: 78 coding sequences, 29 tRNA genes, and four rRNA genes. In addition, a total of 91 SSRs and 43 INEs were found in the M. zhaojiaoensis cp genome, which was slightly different from M. baccata and M. hupehensis in number. The analysis of codon usage and RNA editing showed that high-frequency codons tended to end at A/U bases and RNA editing mainly occurred at the second codon. Comparative genome analysis suggested that the cp genomes of eight Malus species had higher overall similarity, but there were more variation hotspots (rps16_trnK-UUU, trnG-UCC_atpA, atpH_atpF, trnT-GGU_psbD, etc.) in the LSC region. By building evolutionary trees, it can be clearly observed that M. zhaojiaoensis formed a large group with eight species of Malus, but was relatively independent in differentiation. In conclusion, this study provides high-quality chloroplast genome resources of M. zhaojiaoensis and discusses the genetic variation characteristics of Malus genus. The findings of this study will provide a good reference for plastid genome assembly and interspecific comparison in the future.


Assuntos
Genoma de Cloroplastos , Malus , Códon/genética , Uso do Códon/genética , Genoma de Cloroplastos/genética , Filogenia
15.
Opt Lett ; 47(9): 2198-2201, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486759

RESUMO

Asymmetrical directional couplers aided with subwavelength sidewall corrugations are used to realize ultra-compact silicon mode (de)multiplexers at C-band. Three mode (de)multiplexers with ultra-short coupling lengths of 5.6/6.5/7.7 µm are designed to enable low-loss mode conversions between TE0 and TE1/2/3 modes. They are then cascaded to build a four-channel mode-division-multiplexing (MDM) link. The four mode channels present minimal on-chip insertion losses of 0.2/0.7/0.7/0.9 dB at their peak wavelengths. Measured cross talk levels of the four mode channels are better than -18.0/-19.1/-16.0/-18.2 dB within the wavelength range from 1530 nm to 1580 nm.

16.
Front Plant Sci ; 13: 845662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401615

RESUMO

Rosa beggeriana 'Aurea' is a yellow-green leaf (yl) mutant and originated from Rosa beggeriana Schrenk by 60Co-γ irradiation, which is an important ornamental woody species. However, the molecular mechanism of the yl mutant remains unknown. Herein, comparative transcriptome profiling was performed between the yl type and normal green color type (WT) by RNA sequencing. A total of 3,372 significantly differentially expressed genes (DEGs) were identified, consisting of 1,585 upregulated genes and 1,787 downregulated genes. Genes that took part in metabolic of biological process (1,090), membrane of cellular component (728), catalytic (1,114), and binding of molecular function (840) were significantly different in transcription level. DEGs involved in chlorophyll biosynthesis, carotenoids biosynthesis, cutin, suberine, wax biosynthesis, photosynthesis, chloroplast development, photosynthesis-antenna proteins, photosystem I (PSI) and photosystem II (PSII) components, CO2 fixation, ribosomal structure, and biogenesis related genes were downregulated. Meanwhile, linoleic acid metabolism, siroheme biosynthesis, and carbon source of pigments biosynthesis through methylerythritol 4-phosphate (MEP) pathways were upregulated. Moreover, a total of 147 putative transcription factors were signification different expression, involving NAC, WRKY, bHLH, MYB and AP2/ERF, C2H2, GRAS, and bZIP family gene. Our results showed that the disturbed pigments biosynthesis result in yl color by altering the ratio of chlorophylls and carotenoids in yl mutants. The yl mutants may evoke other metabolic pathways to compensate for the photodamage caused by the insufficient structure and function of chloroplasts, such as enhanced MEP pathways and linoleic acid metabolism against oxidative stress. This research can provide a reference for the application of leaf color mutants in the future.

17.
Front Genet ; 13: 846559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401662

RESUMO

Paclobutrazol Resistance (PRE) genes encode atypical basic helix-loop-helix (bHLH) transcription factor family. Typical bHLH proteins contain a bifunctional structure with a basic region involved in DNA binding and an adjacent helix-loop-helix domain involved in protein-protein interaction. PRE members lack the basic region but retain the HLH domain, which interacts with other typical bHLH proteins to suppress or enhance their DNA-binding activity. PRE proteins are involved in phytohormone responses, light signal transduction, and fruit pigment accumulation. However, apple (Malus domestica) PRE protein functions have not been studied. In this study, nine MdPRE genes were identified from the apple GDDH13 v1.1 reference genome and were mapped to seven chromosomes. The cis-acting element analysis revealed that MdPRE promoters possessed various elements related to hormones, light, and stress responses. Expression pattern analysis showed that MdPRE genes have different tissue expression profiles. Hormonal and abiotic stress treatments can induce the expression of several MdPRE genes. Moreover, we provide molecular and genetic evidence showing that MdPRE4.3 increases the apple's sensitivity to NaCl, abscisic acid (ABA), and indoleacetic acid (IAA) and improves tolerance to brassinosteroids (BR); however, it does not affect the apple's response to gibberellin (GA). Finally, the protein interaction network among the MdPRES proteins was predicted, which could help us elucidate the molecular and biological functions of atypical bHLH transcription factors in the apple.

18.
Biomed Res Int ; 2022: 4846279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372576

RESUMO

Aim: In this study, we aimed to investigate the efficacy of catheter directed thrombolysis (CDT) and peripheral intravenous thrombolysis (PIT) in the treatment of patients with acute pulmonary embolism (APE) and assess its effect on the prognosis of patients. Methods: We recruited 74 patients with APE, who were assigned to CDT and PIT groups, according to the treatments received by them. The arterial partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (Pa CO2), pulmonary artery pressure (PAP), pulmonary artery obstruction index (PAOI), thrombus volume, pain score, and therapeutic benefits were compared between the two groups before and after treatment, and the factors affecting patient prognoses were also analyzed. Results: Using the clinical data before treatment as the baseline, it was found that changes in indicators of plasma, thrombus volume, and pain scores were significantly better in the CDT group than in the PIT group after treatment. The total effective rate of CDT was higher than that of PIT in the treatment of APE. The mean follow-up time for both the CDT and PIT groups was 41.08 ± 9.12 months, and the total mortality rate was 14.8% and 31%, respectively. The logistic regression analysis revealed the significant impacts of previous incidences of pulmonary embolism (PE), concurrent deep vein thrombosis (DVT), and pulmonary arterial hypertension (PAH) on the occurrence and progression of APE, and these factors were subsequently identified as risk factors for APE using Kaplan-Meier survival analysis. Observations from PAE onset to the end of follow-up revealed that there was a difference in survival rates between the CDT and PIT groups. Conclusions: Taken together, CDT is an effective treatment strategy for APE and can provide effective symptomatic relief. In addition, the previous incidences of PE, concurrent DVT, and PAH are important risk factors that affect the survival rates of patients with APE.


Assuntos
Embolia Pulmonar , Terapia Trombolítica , Doença Aguda , Cateteres/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemodinâmica , Humanos , Dor/tratamento farmacológico , Prognóstico , Fatores de Tempo , Resultado do Tratamento
19.
Signal Transduct Target Ther ; 7(1): 114, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383141

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Assuntos
Anticorpos Monoclonais , Anticorpos Antivirais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Anticorpos Monoclonais/química , Anticorpos Antivirais/química , COVID-19 , Microscopia Crioeletrônica , Humanos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia
20.
Nurs Res ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35417442

RESUMO

BACKGROUND: The randomized clinical trial is generally considered the most rigorous study design for evaluating overall intervention effects. Due to patient heterogeneity, subgroup analysis is often used to identify differential intervention effects. In research of behavioral interventions, such subgroups often depend on a latent construct measured by multiple correlated observed variables. OBJECTIVES: The purpose of this article is to illustrate latent class analysis/latent profile analysis as a helpful tool to characterize latent subgroups, conduct exploratory subgroup analysis, and identify potential differential intervention effects using clinical trial data. METHODS: After reviewing different approaches for subgroup analysis, latent class analysis/latent profile analysis was chosen to identify heterogeneous patient groups based on multiple correlated variables. This approach is superior in this specific scenario because of its ability to control type I error, assess intersection of multiple moderators, and improve interpretability. We used a case study example to illustrate the process of identifying latent classes as potential moderators based on both clinical and perceived risk scores and then tested the differential effects of health coaching in improving health behavior for patients with elevated risk of developing coronary heart disease. RESULTS: We identified three classes based on one clinical risk score and four perceived risk measures for individuals with high risk of developing coronary heart disease. Compared to other classes we assessed, individuals in the class with low clinical risk and low perceived risk benefit most from health coaching to improve their physical activity levels. DISCUSSION: Latent class analysis/latent profile analysis offers a person-centered approach to identifying distinct patient profiles that can be used as moderators for subgroup analysis. This offers tremendous opportunity to identify differential intervention effects in behavioral research.

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