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1.
BMC Genomics ; 23(1): 651, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100883

RESUMO

BACKGROUND: Alfalfa (Medicago sativa) is a widely cultivated plant. Unlike many crops, the main goal of breeding alfalfa is to increase its aboveground biomass rather than the biomass of its seeds. However, the low yield of alfalfa seeds limits alfalfa production. Many studies have explored the factors affecting seed development, in which phytohormones, especially ABA and GAs, play an important role in seed development. RESULTS: Here, we performed a transcriptome analysis of alfalfa seeds at five development stages. A total of 16,899 differentially expressed genes (DEGs) were identified and classified into 10 clusters, and the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined. The contents of ABA, GA1, GA3, GA4 and GA7 in alfalfa seeds at five development stages were determined. In addition, 14 ABA-related DEGs and 20 GA-related DEGs were identified and analysed. These DEGs are involved in plant hormone pathways and play an important role in seed development. Moreover, morphological and physiological analyses revealed the dynamic changes during the development of alfalfa seeds. CONCLUSION: Overall, our study is the first to analyse the transcriptome across various stages of seed development in alfalfa. The results of our study could be used to improve alfalfa seed yield. The key ABA and GA related-genes are potential targets for improving alfalfa seed yield via genetic engineering in the future.


Assuntos
Ácido Abscísico , Giberelinas , Ácido Abscísico/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Giberelinas/metabolismo , Medicago sativa/genética , Melhoramento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Sementes/metabolismo
2.
Front Plant Sci ; 13: 967432, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110352

RESUMO

Mining novel and less utilized thousand grain weight (TGW) related genes are useful for improving wheat yield. In this study, a recombinant inbred line population from a cross between Zhongkemai 138 (ZKM138, high TGW) and Chuanmai 44 (CM44, low TGW) was used to construct a new Wheat 50K SNP array-derived genetic map that spanned 1,936.59 cM and contained 4, 139 markers. Based on this map, ninety-one quantitative trait loci (QTL) were detected for eight grain-related traits in six environments. Among 58 QTLs, whose superior alleles were contributed by ZKM138, QTgw.cib-6A was a noticeable major stable QTL and was also highlighted by bulked segregant analysis with RNA sequencing (BSR-Seq). It had a pyramiding effect on TGW enhancement but no significant trade-off effect on grain number per spike or tiller number, with two other QTLs (QTgw.cib-2A.2 and QTgw.cib-6D), possibly explaining the excellent grain performance of ZKM138. After comparison with known loci, QTgw.cib-6A was deduced to be a novel locus that differed from nearby TaGW2 and TaBT1. Seven simple sequence repeat (SSR) and thirty-nine kompetitive allele-specific PCR (KASP) markers were finally developed to narrow the candidate interval of QTgw.cib-6A to 4.1 Mb. Only six genes in this interval were regarded as the most likely candidate genes. QTgw.cib-6A was further validated in different genetic backgrounds and presented 88.6% transmissibility of the ZKM138-genotype and a 16.4% increase of TGW in ZKM138 derivatives. And the geographic pattern of this locus revealed that its superior allele is present in only 6.47% of 433 Chinese modern wheat varieties, indicating its potential contribution to further high-yield breeding.

3.
Opt Lett ; 47(18): 4838-4841, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36107103

RESUMO

Dissipative Kerr soliton microcombs are believed to be a promising technique to build a dual-comb source for applications including precision laser metrology, fast laser spectroscopy, and high-speed optical signal processing. In this Letter, we conduct a detailed experimental investigation on the phase coherence between two on-chip Kerr soliton microcombs, where the underlying physical and technical origins that lead to the mutual phase noise between microcombs are analyzed. Moreover, the techniques of 2-point locking and optical frequency division are explored to enhance the dual-microcomb phase coherence, and we demonstrate the best phase noise down to -50 dBc/Hz at 1-Hz offset, -90 dBc/Hz at 1-kHz offset, and -120 dBc/Hz at 1-MHz offset. Our study provides a basic reference for both fundamental studies and practical applications of Kerr soliton dual microcombs that entail high mutual phase coherence.

4.
Plants (Basel) ; 11(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36079635

RESUMO

With the development of the economy and society, more attention is being paid to energy costs and the potential environmental pollution caused by vegetable cultivation. The aim of this study was to investigate the impacts of zero discharge of nutrient solutions on cucumber growth, leaf photosynthesis, and the yield and quality of cucumber under greenhouse conditions. The results show that zero discharge treatment did not change plant height, stem diameter, internode length, leaf area, net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr), and leaf relative chlorophyll content on the most measurement days. Only Pn and relative chlorophyll content were significantly reduced after 16 days of treatment but soon recovered over time. Cucumber plants can adapt to treatment circumstances over the course of days. Leaf mineral element contents showed significant differences on some treatment days compared to the control, and trace elements of Fe, Mn, Cu, and Mo can be appropriately supplied during the treatment days. The cucumber yield and fruit quality in the zero discharge treatment did not change during the whole experimental period. This study confirmed that the irrigation method of a nutrient solution with zero discharge can be applied in cucumber cultivation practices. The strict management of irrigation strategy, plant growth, and greenhouse climate are very important for zero discharge cultivation. The cultivation method with zero discharge of nutrient solution can reduce the energy costs of disinfection, save water and fertilizers, and reduce the environmental pollution in cucumber cultivation.

5.
Contrast Media Mol Imaging ; 2022: 6318051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051921

RESUMO

The anesthetic effect and safety of propofol in craniotomy patients by meta-analysis is investigated. Relevant studies consistent with the anesthetic effect and safety of propofol in craniotomy patients are searched and screened from domestic and foreign literature databases such as Wanfang Medical Center, CNKI, VIP, and PubMed, and meta-analysis is performed by RevMan 5.2 software. Experimental results show that the recovery time, intracranial pressure, cerebral edema, partial cerebral oxygen pressure, glutamate, and MDA in the propofol group are better than those in the control group (P < 0.05), and the incidence of superoxide dismutase, TNF-α, and adr in the propofol group is better than that in the control group (P > 0.05). Intravenous anesthesia with propofol in patients with craniotomy has the advantage of rapid recovery, and this program can improve intracranial pressure, brain edema, and brain oxygen partial pressure and help to improve oxidative stress and inflammatory reaction.


Assuntos
Anestésicos , Propofol , Anestesia Intravenosa , Craniotomia/métodos , Humanos , Oxigênio , Propofol/efeitos adversos
6.
Dalton Trans ; 51(37): 14214-14220, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36062936

RESUMO

In this work, a series of Cr3+-doped A2NaYF6 (denoted as ANYF:Cr; A = K, Rb, and Cs) fluoroyttrate double-perovskites with broad blue excitation and near-infrared (NIR) emission bands were prepared using a high-temperature solid-state reaction method. The physicochemical and spectroscopic properties of the as-prepared products, including crystal structure, bandgap, morphology, luminescence behaviour and optical performance, were studied in detail. The results show that the Cr3+ activators undergo a decreasing crystal field in ANYF in the direction from K to Cs, yielding a red shift of the emission peak position from 758 to 786 nm, whilst the full-width-at-half-maximum (FWHM) expands from 98 to 104 nm. By virtue of the broadband NIR emission, clear structural images of the tangerine section, mini LED flashlight and circuit board were obtained by merging the optimal RNYF:Cr phosphor on a blue InGaN chip, implying its potential use in light-emitting diodes for non-destructive testing.

7.
Infect Drug Resist ; 15: 4887-4898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051656

RESUMO

Background: Candida bloodstream infection (BSI), the fourth most common nosocomial BSI, is an urgent global health challenge with the tremendous growth in antifungal resistance rate and mortality rate. Purpose: To establish the epidemiology, species distribution, risk factors, and 30-day mortality of candidaemia among 115 patients in this 6-year surveillance study. Materials and Methods: We retrospectively analyzed the clinical characteristics, epidemiology, antifungal susceptibility patterns, and risk factors for morbidity and mortality of 115 candidaemia cases diagnosed in one tertiary care hospital from January 2016 through December 2021. Results: Of the 115 candidaemia cases, the most prevalent species were Candida tropicalis (33.0%), followed by Candida albicans (27.8%), Candida parapsilosis complex (19.1%), and others. The overall incidence was 0.21 cases/1000 admissions. The overall crude resistance rate of Candida spp. against azoles was 20.0% (23/115), while Candida tropicalis showed a significant increase in the resistance rate to azoles (from 1/6, 16.7% in 2017 to 6/10, 60.0% in 2021). Multivariate analyses demonstrated that hematological malignancy and neutropenia were significantly associated with Candida tropicalis BSI than Candida non-tropicalis BSI. Candida albicans BSI had a significantly higher rate of previous surgery than Candida non-albicans BSI. Candida parapsilosis BSI had a significantly higher rate of receiving total parenteral nutrition (TPN). The overall 30-day mortality rate was 27.0% (31/115). The presence of high age-adjusted Charlson comorbidity index (aCCI), neutropenia, and septic shock were factors independently associated with increased 30-day mortality. Conclusion: Candida tropicalis are emerging as the predominant isolate in candidaemia. Of note, the unexpectedly increased resistance rate to azoles in Candida tropicalis BSI was observed. The aCCI scores, neutropenia, and septic shock were independently associated with 30-day mortality. Prompt, adequate antifungal treatment among high-risk patients may lead to a reduction in mortality.

8.
World Neurosurg ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36058485

RESUMO

BACKGROUND: Microsurgical techniques are increasingly being recommended for the treatment of symptomatic Tarlov cysts (TCs) due to improved long-term outcomes compared to those of other strategies. However, these techniques are associated with a high risk of cyst recurrence and cerebrospinal fluid (CSF) leakage, resulting in the surgical strategy of TCs remaining controversial. We hypothesize that incomplete closure of the ostium between the cyst and the subarachnoid space is the probable cause of surgical failure. Accordingly, we present a novel method of cyst separation and ostium closure that aims to block the ostium more firmly and reliably. METHODS: Thirty-five consecutive patients (21 females) underwent the modified ostium obstruction surgery due to symptomatic TCs. We collected and compared their outcomes at the final follow-up to evaluate the surgical effect. RESULTS: Thirty-five patients had 74 TCs (S2 level, 48.7%; mean diameter, 2.0 ± 1.0 cm); ostia nerve root fibers were found in all TCs. The mean follow-up duration was 37.8 (range, 13.5-76.8) months. At the final follow-up, 33 patients experienced complete or substantial resolution of the preoperative symptoms. The symptom with the highest improvement rate was radicular pain. Both the modified evaluation criteria for the efficacy of lumbar function criterion and Japanese Orthopedic Association score 29 showed an overall improvement rate of 94.3%. Two patients experienced surgery-related neurological dysfunction. No cyst recurrence or CSF leakage was observed. Magnetic resonance imaging showed that all cysts disappeared or significantly reduced postoperatively. CONCLUSIONS: The microscopic fenestration of cysts and modified ostium obstruction described herein is a safe and effective strategy for management of patients with symptomatic TCs and is associated with a low incidence of cyst recurrence and CSF leakage since it achieves complete closure of cyst ostium.

9.
J Med Virol ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127294

RESUMO

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

10.
Front Mol Neurosci ; 15: 974060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157079

RESUMO

Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA-DEmiRNA-DEmRNA and DElncRNA-DEmiRNA-DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI.

11.
Theor Appl Genet ; 135(10): 3643-3660, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057866

RESUMO

KEY MESSAGE: Rht22 was fine mapped in the interval of 0.53-1.48 Mb on 7AS, which reduces cell number of internode to cause semi-dwarfism in Jianyangailanmai. As a valuable germplasm resource for wheat genetic improvement, tetraploid wheat has several reduced height (Rht) and enhanced harvest index genes. Rht22, discovered in Jianyangailanmai (JAM, Triticum turgidum L., 2n = 4x = 28, AABB), significantly increases the spikelet number per spike, but its accurate chromosomal position is still unknown. In this study, a high-density genetic map was constructed using specific-length amplified fragment sequencing in an F7 RIL_DJ population, which was derived from a cross between dwarf Polish wheat (T. polonicum L., 2n = 4x = 28, AABB) and JAM. Two plant height loci, Qph.sicau-4B and Qph.sicau-7A, were mapped on chromosomes 4BS and 7AS, respectively. Qph.sicau-7A was mapped to the 0.33-4.46 Mb interval on 7AS and likely represents the candidate region of Rht22. Fine mapping confirmed and narrowed Rht22 on chromosome arm 7AS between Xbag295.s53 and Xb295.191 in three different populations. The physical region ranged from 0.53 to 1.48 Mb and included 18 candidate genes. Transcriptome analysis of two pairs of near-isogenic lines revealed that 135 differentially expressed genes (DEGs) were associated with semi-dwarfism. Of these, the expression of 83 annotated DEGs involved in hormones synthesis and signal transduction, cell wall composition, DNA replication, microtubule and phragmoplast arrays was significantly down-regulated in the semi-dwarf line. Therefore, Rht22 causes semi-dwarfism in JAM by disrupting these cellular processes, which impairs cell proliferation and reduces internode cell number.


Assuntos
Nanismo , Triticum , Mapeamento Cromossômico , Nanismo/genética , Hormônios , Fenótipo , Locos de Características Quantitativas , Tetraploidia , Triticum/genética
12.
Int J Nanomedicine ; 17: 4277-4292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36134200

RESUMO

Purpose: The objective of this study was to evaluate and compare the histopathological implications of silica nanoparticles (Nano-SiO2) and indium-tin oxide nanoparticles (Nano-ITO), in vivo. Methods: Male Sprague-Dawley rats were exposed to Nano-SiO2 (50 mg/kg) and Nano-ITO (6 mg/kg) by a single intratracheal instillation, respectively. Broncho-alveolar lavage fluid (BALF) and lung tissue were obtained at 7, 14, 28, and 56 days post exposure for analysis of BALF inflammatory factors, total protein, and for lung tissue pathology. Histopathological and ultrastructural change in lungs were investigated by hematoxylin and eosin, Masson's trichrome, sirius red staining, periodic acid Schiff stain, and transmission electron microscopy. The expression of SP-A, collagen type I and III in lung tissue was determined by immunohistochemistry and ELISA. Results: The rats in both models exhibited obvious collagen fibrosis and the severity of the lung injury increased with time after exposure to respective dosage increased. Several parameters of pulmonary inflammation and fibrosis significantly increased in both groups, which was reflected by increased LDH activity, total proteins, TNF-α, and IL-6 levels in BALF, and confirmed by histopathological examination. The results also showed that the two models exhibited different features. Exposure to Nano-ITO caused persistent chronic lung inflammation, illustrated by the infiltration of a large amount of enlarged and foamy macrophages and neutrophils into the lung parenchyma. In Nano-SiO2 exposed rat lung tissue, granulomatous inflammation was most prominent followed by progressive and massive fibrotic nodules. Compared with the Nano-SiO2 rats, Nano-ITO exposed rats exhibited significantly severe pulmonary alveolar proteinosis (PAP) pathological changes, lower fibrosis, and higher levels of inflammatory biomarkers. However, Nano-SiO2 exposed rats had greater fibrosis pathological changes and more severe granulomas than Nano-ITO exposed rats. Conclusion: This study suggests that the Nano-SiO2-induced model has greater value in research into granulomas and fibrosis, while the Nano-ITO-induced model has greater repeatability in area of PAP.


Assuntos
Nanopartículas , Pneumonia , Animais , Líquido da Lavagem Broncoalveolar , Colágeno Tipo I/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Fibrose , Hematoxilina/metabolismo , Índio , Interleucina-6/metabolismo , Pulmão/patologia , Masculino , Nanopartículas Metálicas , Nanopartículas/toxicidade , Ácido Periódico/metabolismo , Pneumonia/patologia , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/toxicidade , Compostos de Estanho , Fator de Necrose Tumoral alfa/metabolismo
13.
Front Genet ; 13: 978880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092872

RESUMO

Wheat is one of the most important staple crops for supplying nutrition and energy to people world. A new genetic map based on the Wheat 55 K SNP array was constructed using recombinant inbred lines derived from a cross between Zhongkemai138 and Kechengmai2 to explore the genetic foundation for wheat grain features. This new map covered 2,155.72 cM across the 21 wheat chromosomes with 11,455 markers. And 2,846 specific markers for this genetic map and 148 coincident markers among different maps were documented, which was helpful for improving and updating wheat genetic and genomic information. Using this map, a total of 68 additive QTLs and 82 pairs of epistatic QTLs were detected for grain features including yield, nutrient composition, and quality-related traits by QTLNetwork 2.1 and IciMapping 4.1 software. Fourteen additive QTLs and one pair of epistatic QTLs could be detected by both software programs and thus regarded as stable QTLs here, all of which explained higher phenotypic variance and thus could be utilized for wheat grain improvement. Additionally, thirteen additive QTLs were clustered into three genomic intervals (C4D.2, C5D, and C6D2), each of which had at least two stable QTLs. Among them, C4D.2 and C5D have been attributed to the famous dwarfing gene Rht2 and the hardness locus Pina, respectively, while endowed with main effects on eight grain yield/quality related traits and epistatically interacted with each other to control moisture content, indicating that the correlation of involved traits was supported by the pleotropic of individual genes but also regulated by the gene interaction networks. Additionally, the stable additive effect of C6D2 (QMc.cib-6D2 and QTw.cib-6D2) on moisture content was also highlighted, potentially affected by a novel locus, and validated by its flanking Kompetitive Allele-Specific PCR marker, and TraesCS6D02G109500, encoding aleurone layer morphogenesis protein, was deduced to be one of the candidate genes for this locus. This result observed at the QTL level the possible contribution of grain water content to the balances among yield, nutrients, and quality properties and reported a possible new locus controlling grain moisture content as well as its linked molecular marker for further grain feature improvement.

14.
BMC Genomics ; 23(1): 639, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076168

RESUMO

BACKGROUND: Sinosenecio B. Nordenstam (Asteraceae) currently comprises 44 species. To investigate the interspecific relationship, several chloroplast markers, including ndhC-trnV, rpl32-trnL, matK, and rbcL, are used to analyze the phylogeny of Sinosenecio. However, the chloroplast genomes of this genus have not been thoroughly investigated. We sequenced and assembled the Sinosenecio albonervius chloroplast genome for the first time. A detailed comparative analysis was performed in this study using the previously reported chloroplast genomes of three Sinosenecio species. RESULTS: The results showed that the chloroplast genomes of four Sinosenecio species exhibit a typical quadripartite structure. There are equal numbers of total genes, protein-coding genes and RNA genes among the annotated genomes. Per genome, 49-56 simple sequence repeats and 99 repeat sequences were identified. Thirty codons were identified as RSCU values greater than 1 in the chloroplast genome of S. albonervius based on 54 protein-coding genes, indicating that they showed biased usage. Among 18 protein-coding genes, 46 potential RNA editing sites were discovered. By comparing these chloroplast genomes' structures, inverted repeat regions and coding regions were more conserved than single-copy and non-coding regions. The junctions among inverted repeat and single-copy regions showed slight difference. Several hot spots of genomic divergence were detected, which can be used as new DNA barcodes for species identification. Phylogenetic analysis of the whole chloroplast genome showed that the four Sinosenecio species have close interspecific relationships. CONCLUSIONS: The complete chloroplast genome of Sinosenecio albonervius was revealed in this study, which included a comparison of Sinosenecio chloroplast genome structure, variation, and phylogenetic analysis for related species. These will help future research on Sinosenecio taxonomy, identification, origin, and evolution to some extent.


Assuntos
Asteraceae , Genoma de Cloroplastos , Asteraceae/genética , Cloroplastos/genética , Repetições de Microssatélites/genética , Filogenia
15.
Exp Neurol ; 358: 114224, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36089058

RESUMO

Memory extinction and renewal are major factors that limits the efficacy of exposure therapy. The dorsal dentate gyrus (dDG) plays a crucial role in spatial memory, and epigenetic modifications in the dDG play an important role in fear memory renewal. However, whether dDG activity regulates fear memory extinction and renewal remains unclear. In this study, we showed that an extinction procedure that prevents fear memory renewal (extinction within the reconsolidation window) leads to increased c-fos expression in the dDG. Chemicogenetic activation of dDG excitatory neurons during extinction training elevated fear memory extinction and prevented renewal, whereas inhibition of dDG excitatory neurons inhibited fear memory extinction. We also demonstrated that inhibiting fear engram cells (neurons active during fear acquisition) during extinction training inhibits fear memory extinction. Therefore, dDG activity during fear extinction plays an important role in fear memory extinction and renewal.

17.
Ecotoxicol Environ Saf ; 245: 114100, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36155331

RESUMO

Silicosis is a severe progressive lung disease without effective treatment methods. Previous evidence has demonstrated that endothelial cell to mesenchymal transition (EndoMT) plays an essential role in pulmonary fibrosis, and pulmonary fibrosis is associated with dysregulation of autophagy, while the relationship between autophagy and EndoMT has not yet been adequately studied. Herein, we established a mouse model of silicosis, and we found that the pharmacological induction of the AMPK/mTOR-dependent pathway using 100 mg/kg Metformin (Met) enhanced autophagy in vivo, and results of the Western blot showed that autophagy-related proteins, LC3 II/I ratio, and Beclin-1 increased while p62 decreased. In addition, Met treatment attenuated silica-induced pulmonary inflammation and decreased collagen deposition by suppressing EndoMT, and the proliferation of human umbilical vein endothelial cells (HUVECs) was also inhibited. Notably, the tube forming assay showed that Met also protected the vascular endothelial cells from silica-induced morphological damage. In conclusion, Met can alleviate inflammatory response and collagen deposition in the process of pulmonary fibrosis induced by silica via suppressing EndoMT through the AMPK/mTOR signaling pathway.

18.
Redox Biol ; 56: 102458, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116159

RESUMO

Guanosine triphosphate binding protein 4 (GTPBP4) is a key regulator of cell cycle progression and MAPK activation. However, how its biological properties intersect with cellular metabolism in hepatocellular carcinoma (HCC) development remains poorly unexplained. Here, high GTPBP4 expression is found to be significantly associated with worse clinical outcomes in patients with HCC. Moreover, GTPBP4 upregulation is paralleled by DNA promoter hypomethylation and regulated by DNMT3A, a DNA methyltransferase. Additionally, both gain- and loss-of-function studies demonstrate that GTPBP4 promotes HCC growth and metastasis in vitro and in vivo. Mechanically, GTPBP4 can induce dimeric pyruvate kinase M2 (PKM2) formation through protein sumoylation modification to promote aerobic glycolysis in HCC. Notably, active GTPBP4 facilitates SUMO1 protein activation by UBA2, and acts as a linker bridging activated SUMO1 protein and PKM2 protein to induce PKM2 sumoylation. Furthermore, SUMO-modified PKM2 relocates from the cytoplasm to the nucleus may also could contribute to HCC progression through activating epithelial-mesenchymal transition (EMT) and STAT3 signaling pathway. Shikonin, a PKM2-specific inhibitor, can attenuate PKM2 dependent HCC glycolytic reprogramming, growth and metastasis promoted by GTPBP4, which offers a promising therapeutic candidate for HCC patients. Our findings indicate that GTPBP4-PKM2 regulatory axis plays a vital role in promoting HCC proliferation as well as metastasis by aerobic glycolysis and offer a promising therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular , Proteínas de Ligação ao GTP , Neoplasias Hepáticas , Proteínas Nucleares , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , DNA/metabolismo , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Glucose/metabolismo , Glicólise , Humanos , Neoplasias Hepáticas/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas Nucleares/metabolismo , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo
19.
J Exp Clin Cancer Res ; 41(1): 253, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986343

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, the potential mechanisms of the immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear. METHODS: The candidate long non-coding RNAs (lncRNAs) were screened by Smart-seq based scRNA-seq method and then validated by qPCR. Immunostaining analysis was done to examine the levels of markers for TAMs and glycolysis. Exosomes from primary TAMs of human HCC tissues were isolated by centrifugation, and their internalization with lncRNAs was confirmed by immunofluorescence. The underlying mechanism of TAMs-derived exosomal lncRNA to HCC was confirmed by luciferase reporter assay and RNA immunoprecipitation. Metabolism regulation was evaluated through glucose consumption, lactate productions and extracellular acidification rates (ECARs). Mouse xenograft models were used to elucidate the in vivo effect of candidate lncRNAs on tumor growth. RESULTS: TAMs augment the aerobic glycolysis in HCC cells and their proliferation by the extracellular exosome transmission of a myeloid-derived lncRNA, M2 macrophage polarization associated lncRNA (lncMMPA). Mechanistically, lncMMPA not only could polarize M2 macrophage, but also could act as an microRNA sponge to interact with miR-548 s and increase the mRNA level of ALDH1A3, then further promote glucose metabolism and cell proliferation in HCC. Moreover, lncMMPA increased HCC cell multiplication through interacting with miR-548 s in vivo. Clinically, lncMMPA expression associates with glycolysis in TAMs and reduced survival of HCC patients. CONCLUSION: LncMMPA plays an important role in regulating HCC malignancy and metabolic reprogramming of miR-548 s/ALDH1A3 pathway.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Neoplasias Hepáticas/patologia , Camundongos , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor
20.
Anal Bioanal Chem ; 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36018334

RESUMO

Exhaled volatile organic compounds (VOCs) have been widely applied for the study of disease biomarkers. Oral exhalation and nasal exhalation are two of the most common sampling methods. However, VOCs released from food residues and bacteria in the mouth or upper respiratory tract were also sampled and usually mistaken as that produced from body metabolism. In this study, exhalation from deep airway was first directly collected through intubation sampling and analyzed. The exhalation samples of 35 subjects were collected through a catheter, which was inserted into the trachea or bronchus through the mouth and upper respiratory tract. Then, the VOCs in these samples were detected by proton transfer reaction mass spectrometry (PTR-MS). In addition, fast gas chromatography proton transfer reaction mass spectrometry (FGC-PTR-MS) was used to further determine the VOCs with the same mass-to-charge ratios. The results showed that there was methanol, acetonitrile, ethanol, methyl mercaptan, acetone, isoprene, and phenol in the deep airway. Compared with that in oral exhalation, ethanol, methyl mercaptan, and phenol had lower concentrations. In detail, the median concentrations of ethanol, methyl mercaptan, and phenol were 7.3, 0.6, and 23.9 ppbv, while those in the oral exhalation were 80.0, 5.1, and 71.3 ppbv, respectively, which meant the three VOCs mainly originated from the food residues and bacteria in the mouth or upper respiratory tract, rather than body metabolism. The research results in our study can provide references for expiratory VOC research based on oral and nasal exhalation samplings, which are more feasible in clinical practice.

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