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1.
PLoS Genet ; 20(4): e1011237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38662763

RESUMO

An animal's skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR-14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.


Assuntos
Conexinas , Dendritos , Proteínas de Drosophila , Epiderme , Larva , MicroRNAs , Nociceptores , Animais , Larva/genética , Dendritos/metabolismo , Dendritos/fisiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Nociceptores/metabolismo , Epiderme/metabolismo , Drosophila melanogaster/genética , Células Epidérmicas/metabolismo , Nociceptividade/fisiologia , Drosophila/genética
2.
Plant J ; 118(2): 549-564, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38184780

RESUMO

Epigenetic regulation of gene expression plays a crucial role in plant development and environmental adaptation. The H3K4me3 and H3K27me3 have not only been discovered in the regulation of gene expression in multiple biological processes but also in responses to abiotic stresses in plants. However, evidence for the presence of both H3K4me3 and H3K27me3 on the same nucleosome is sporadic. Cold-induced deposition of bivalent H3K4me3-H3K27me3 modifications and nucleosome depletion over a considerable number of active genes is documented in potato tubers and provides clues on an additional role of the bivalent modifications. Limited by the available information of genes encoding PcG/TrxG proteins as well as their corresponding mutants in potatoes, the molecular mechanism underlying the cold-induced deposition of the bivalent mark remains elusive. In this study, we found a similar deposition of the bivalent H3K4me3-H3K27me3 mark over 2129 active genes in cold-treated Arabidopsis Col-0 seedlings. The expression levels of the bivalent mark-associated genes tend to be independent of bivalent modification levels. However, these genes were associated with greater chromatin accessibility, presumably to provide a distinct chromatin environment for gene expression. In mutants clf28 and lhp1, failure to deposit H3K27me3 in active genes upon cold treatment implies that the CLF is potentially involved in cold-induced deposition of H3K27me3, with assistance from LHP1. Failure to deposit H3K4me3 during cold treatment in atx1-2 suggests a regulatory role of ATX1 in the deposition of H3K4me3. In addition, we observed a cold-induced global reduction in nucleosome occupancy, which is potentially mediated by LHP1 in an H3K27me3-dependent manner.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Histonas/genética , Histonas/metabolismo , Nucleossomos/genética , Nucleossomos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Epigênese Genética , Proteínas de Arabidopsis/metabolismo , Cromatina/genética , Cromatina/metabolismo , Regulação da Expressão Gênica de Plantas/genética
3.
Thromb J ; 22(1): 11, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229151

RESUMO

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

4.
Xenobiotica ; 54(5): 248-256, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38634734

RESUMO

Prostate inflammation is often treated with drugs which are ineffective. Antibacterial agents fail to reach the prostate epithelium, and the blood-prostate barrier (BPB) may affect the drug transport process. Factors affecting drug efficacy remain unclear.Rats were categorised into groups A and B, corresponding to adulthood and puberty, respectively. Group C included the model of chronic prostate infection. Dialysates of levofloxacin and cefradine were collected from the prostate gland and jugular vein and evaluated. Pharmacokinetic analysis was conducted.The free concentrations of antimicrobials in the prostate and plasma samples of all groups peaked at 20 min, then gradually decreased. The mean AUC0-tprostate/AUC0-tplasma ratio in the levofloxacin group were 0.86, 0.53, and 0.95, and the mean values of AUC0-∞prostate/AUC0-∞plasma ratio were 0.85, 0.63, and 0.97. The corresponding values in the cefradine group were 0.67, 0.30 and 0.84, and 0.66, 0.31, and 0.85, respectively. The mean values in group B were lower than those in group A, and those in group C were higher than those in group B.The maturity of the prostate may affect the ability of the drug to cross the BPB. Infection may disrupt the BPB, affecting drug permeability.


Assuntos
Antibacterianos , Levofloxacino , Próstata , Masculino , Animais , Próstata/metabolismo , Ratos , Levofloxacino/farmacocinética , Antibacterianos/farmacocinética
5.
Photodermatol Photoimmunol Photomed ; 40(1): e12950, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288763

RESUMO

AIM: Lithospermum erythrorhizon and Pueraria lobata exhibit promising potential as cosmetic additives for mitigating skin barrier impairment induced by photoaging. Despite their potential, the precise mechanisms underlying their protective and ameliorative effects remain elusive. This study sought to assess the reparative properties of Lithospermum erythrorhizon and Pueraria lobata extracts (LP) on UVB-irradiated human skin keratinocytes (HaCaT cells) and explore the therapeutic potential of LP as a skin barrier protection agent. MATERIALS AND METHODS: Antioxidant activities were gauged through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reactive oxygen species (ROS) assays. The expression levels of skin barrier-related markers, encompassing metalloproteinases (MMPs) and hyaluronidase (HYAL) were scrutinized using enzyme-linked immunosorbent assay (ELISA), reverse transcriptase (RT)-PCR, and Western blotting, with a particular focus on the involvement of the transforming growth factor (TGF)-ß/Smad and nuclear factor-κB (NF-κB) signaling pathways. RESULTS: The study revealed that LP effectively scavenges free radicals, diminishes ROS production in a dose-dependent manner, and significantly attenuates UVB-induced expression of MMP-1 and MMP-3 through modulation of the hyaluronan synthase (HAS)2/HYAL1 signaling axis in UVB-irradiated HaCaT cells. Additionally, LP demonstrated enhanced TGF-ß signaling activation, fostering procollagen type I synthesis, and concurrently exhibited mitogen-activated protein kinases (MAPK)/NF-κB signaling inactivation, thereby mitigating pro-inflammatory cytokine release and alleviating UVB-induced cellular damage. CONCLUSION: In conclusion, the observed protective effects of LP on skin cellular constituents highlight its substantial biological potential for shielding against UVB-induced skin photoaging, positioning it as a promising candidate for both pharmaceutical and cosmetic applications.


Assuntos
Lithospermum , Pueraria , Envelhecimento da Pele , Dermatopatias , Humanos , Pueraria/metabolismo , Lithospermum/metabolismo , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Raios Ultravioleta/efeitos adversos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fibroblastos/metabolismo
6.
Chin Med Sci J ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38769053

RESUMO

Objectives Renal replacement therapy (RRT) is increasingly adopted for critically ill patients diagnosed with acute kidney injury, but the optimal time for initiation remains unclear and prognosis is uncertain, leading to medical complexity, ethical conflicts, and decision dilemmas in intensive care unit (ICU) settings. This study aimed to develop a decision aid (DA) for family surrogate of critically ill patients to support their engagement in shared decision-making process with clinicians. Methods Development of DA employed a systematic process with user-centered design (UCD) principle, which included: (i) competitive analysis: searched, screened, and assessed the existing DAs to gather insights for design strategies, developmental techniques, and functionalities; (ii) user needs assessment: interviewed family surrogates to explore target user group's decision-making experience and identify their unmet needs; (iii) evidence syntheses: integrate latest clinical evidence and pertinent information to inform the content development of DA.Results The competitive analysis included 16 relevant DAs, from which we derived valuable insights from existing resources. User decision needs were explored among a cohort of 15 family surrogates, revealing four thematic issues in decision-making, including stuck into dilemmas, sense of uncertainty, limited capacity, and delayed decision confirmation. A total of 27 articles were included for evidence syntheses. Relevant decision-making knowledge on disease and treatment, as delineated in the literature sourced from decision support system or clinical guidelines, were formatted as the foundational knowledge base. Twenty-one items of evidence were extracted and integrated into the content panels of benefits and risks of RRT, possible outcomes, and reasons to choose. The DA was drafted into a web-based phototype using the elements of UCD. This platform could guide users make preparation of decision-making through a sequential four-step progress: identifying treatment options, weighing the benefits and risks, clarifying personal preferences and values, and formulating a schedule for formal shared decision-making with clinicians.Conclusions We developed a rapid prototype of DA tailored for family surrogate decision makers of critically ill patients in need of RRT in ICU setting. Future studies are needed to evaluate its usability, feasibility, and clinical effects of this intervene.

7.
Chemistry ; 29(29): e202300184, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36894502

RESUMO

Carboxylic acids are abundant, low cost and environmentally friendly, direct convert carboxylic acids into valued-added compounds are in high demand. Herein, we report a Rh(I) catalyzed direct decarbonylative borylation of aryl and alkyl carboxylic acid using TFFH as activator. This protocol features excellent functional-group tolerance and a broad substrate scope including natural product and drugs. A gram-scale decarbonylative borylation reaction of Probenecid is also presented. In addition, the utility of this strategy is highlighted by a one-pot decarbonylative borylation/ derivatization sequence.

8.
Microb Ecol ; 85(4): 1434-1447, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35420314

RESUMO

The efficacy of nitrification inhibitors (NIs) dicyandiamide (DCD) and 3,4-dimethylpyrazole phosphate (DMPP) varies with soil types. Understanding the microbial mechanisms for this variation may lead to better modelling of NI efficacy and therefore on-farm adoption. This study addressed the response patterns of mineral nitrogen, nitrous oxide (N2O) emission, abundances of N-cycling functional guilds and soil microbiota characteristics, in relation to urea application with or without DCD or DMPP in two arable soils (an alkaline and an acid soil). The inhibition of nitrification rate and N2O emission by NI application occurred by suppressing ammonia-oxidizing bacteria (AOB) abundances and increasing the abundances of nosZI-N2O reducers; however, abundances of ammonia-oxidizing archaea (AOA) were also stimulated with NIs-added in these two arable soils. DMPP generally had stronger inhibition efficiency than DCD, and both NIs' addition decreased Nitrobacter, while increased Nitrospira abundance only in alkaline soil. N2O emissions were positively correlated with AOB and negatively correlated with nosZI in both soils and AOA only in acid soil. Moreover, N2O emissions were also positively correlated with nirK-type denitrifiers in alkaline soil, and clade A comammox in acid soil. Amendment with DCD or DMPP altered soil microbiota community structure, but had minor effect on community composition. These results highlight a crucial role of the niche differentiation among canonical ammonia oxidizers (AOA/AOB), Nitrobacter and Nitrospira, as well as nosZI- and nosZII-N2O reducers in determining the varying efficacies of DCD and DMPP in different arable soils.


Assuntos
Betaproteobacteria , Solo , Solo/química , Nitrificação , Iodeto de Dimetilfenilpiperazina/farmacologia , Fosfatos , Amônia , Microbiologia do Solo , Archaea , Bactérias , Oxirredução
9.
Int J Mol Sci ; 24(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37569498

RESUMO

Bile acids (BAs) are well known to facilitate the absorption of dietary fat and fat-soluble molecules. These unique steroids also function by binding to the ubiquitous cell membranes and nuclear receptors. As chemical signals in gut-liver axis, the presence of metabolic disorders such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and even tumors have been reported to be closely related to abnormal levels of BAs in the blood and fecal metabolites of patients. Thus, the gut microbiota interacting with BAs and altering BA metabolism are critical in the pathogenesis of numerous chronic diseases. This review intends to summarize the mechanistic links between metabolic disorders and BAs in gut-liver axis, and such stage-specific BA perturbation patterns may provide clues for developing new auxiliary diagnostic means.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Ácidos e Sais Biliares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Biomarcadores/metabolismo
10.
Int J Mol Sci ; 24(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37629094

RESUMO

Large White pigs are extensively utilized in China for their remarkable characteristics of rapid growth and the high proportion of lean meat. The economic traits of pigs, comprising reproductive and meat quality traits, play a vital role in swine production. In this study, 2295 individuals, representing three different genetic backgrounds Large White pig populations were used: 500 from the Canadian line, 295 from the Danish line, and 1500 from the American line. The GeneSeek 50K GGP porcine HD array was employed to genotype the three pig populations. Firstly, genomic selective signature regions were identified using the pairwise fixation index (FST) and locus-specific branch length (LSBL). By applying a top 1% threshold for both parameters, a total of 888 candidate selective windows were identified, harbouring 1571 genes. Secondly, the investigation of regions of homozygosity (ROH) was performed utilizing the PLINK software. In total, 25 genomic regions exhibiting a high frequency of ROHs were detected, leading to the identification of 1216 genes. Finally, the identified potential functional genes from candidate genomic regions were annotated, and several important candidate genes associated with reproductive traits (ADCYAP1, U2, U6, CETN1, Thoc1, Usp14, GREB1L, FGF12) and meat quality traits (MiR-133, PLEKHO1, LPIN2, SHANK2, FLVCR1, MYL4, SFRP1, miR-486, MYH3, STYX) were identified. The findings of this study provide valuable insights into the genetic basis of economic traits in Large White pigs and may have potential use in future pig breeding programs.


Assuntos
Genômica , MicroRNAs , Animais , Suínos/genética , Canadá , Homozigoto , Genótipo
11.
Theor Appl Genet ; 135(9): 3265-3276, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35882642

RESUMO

KEY MESSAGE: Twelve QTL associated with pre-harvest sprouting tolerance were identified using association analysis in wheat. Two markers were validated and a candidate gene TaNAC074 for Qgpf.cas-3B.2 was verified using Agrobacterium-mediated transformation. Pre-harvest sprouting (PHS) is a considerable global threat to wheat yield and quality. Due to this threat, breeders must identify quantitative trait loci (QTL) and genes conferring PHS-tolerance (PHST) to reduce the negative effects of PHS caused by low seed dormancy. In this study, we evaluated a panel of 302 diverse wheat genotypes for PHST in four environments and genotyped the panel with a high-density wheat 660 K SNP array. By using a genome-wide association study (GWAS), we identified 12 stable loci significantly associated with PHST (P < 0.0001), explaining 3.34 - 9.88% of the phenotypic variances. Seven of these loci co-located with QTL and genes reported previously. Five loci (Qgpf.cas-3B.2, Qgpf.cas-3B.3, Qgpf.cas-3B.4, Qgpf.cas-7B.2, and Qgpf.cas-7B.3), located in genomic regions with no known PHST QTL or genes, are likely to be new QTL conferring PHST. Additionally, two molecular markers were developed for Qgpf.cas-3A and Qgpf.cas-7B.3, and validated using a different set of 233 wheat accessions. Finally, the PHST-related function of candidate gene TaNAC074 for Qgpf.cas-3B.2 was confirmed by CAPS (cleaved amplified polymorphic sequences) marker association analysis in 233 wheat accessions and by expression and phenotypic analysis of transgenic wheat. Overexpression of TaNAC074 significantly reduced seed dormancy in wheat. This study contributes to broaden the genetic basis and molecular marker-assisted breeding of PHST.


Assuntos
Estudo de Associação Genômica Ampla , Triticum , Mapeamento Cromossômico , Marcadores Genéticos , Melhoramento Vegetal , Fatores de Transcrição/genética , Triticum/genética
12.
Eur Radiol ; 32(8): 5179-5188, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35175380

RESUMO

OBJECTIVES: To explore downstream management and outcomes of machine learning (ML)-based CT derived fractional flow reserve (FFRCT) strategy compared with an anatomical coronary computed tomography angiography (CCTA) alone assessment in participants with intermediate coronary artery stenosis. METHODS: In this prospective study conducted from April 2018 to March 2019, participants were assigned to either the CCTA or FFRCT group. The primary endpoint was the rate of invasive coronary angiography (ICA) that demonstrated non-obstructive disease at 90 days. Secondary endpoints included coronary revascularization and major adverse cardiovascular events (MACE) at 1-year follow-up. RESULTS: In total, 567 participants were allocated to the CCTA group and 566 to the FFRCT group. At 90 days, the rate of ICA without obstructive disease was higher in the CCTA group (33.3%, 39/117) than that (19.8%, 19/96) in the FFRCT group (risk difference [RD] = 13.5%, 95% confidence interval [CI]: 8.4%, 18.6%; p = 0.03). The ICA referral rate was higher in the CCTA group (27.5%, 156/567) than in the FFRCT group (20.3%, 115/566) (RD = 7.2%, 95% CI: 2.3%, 12.1%; p = 0.003). The revascularization-to-ICA ratio was lower in the CCTA group than that in the FFRCT group (RD = 19.8%, 95% CI: 14.1%, 25.5%, p = 0.002). MACE was more common in the CCTA group than that in the FFRCT group at 1 year (HR: 1.73; 95% CI: 1.01, 2.95; p = 0.04). CONCLUSION: In patients with intermediate stenosis, the FFRCT strategy appears to be associated with a lower rate of referral for ICA, ICA without obstructive disease, and 1-year MACE when compared to the anatomical CCTA alone strategy. KEY POINTS: • In stable patients with intermediate stenosis, ML-based FFRCT strategy was associated with a lower referral ICA rate, a lower normalcy rate of ICA, and higher revascularization-to-ICA ratio than the CCTA strategy. • Compared with the CCTA strategy, ML-based FFRCTshows superior outcome prediction value which appears to be associated with a lower rate of 1-year MACE. • ML-based FFRCT strategy as a non-invasive "one-stop-shop" modality may be the potential to change diagnostic workflows in patients with suspected coronary artery disease.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Angiografia por Tomografia Computadorizada/métodos , Constrição Patológica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Valor Preditivo dos Testes , Estudos Prospectivos , Tomografia Computadorizada por Raios X
13.
Cryobiology ; 109: 37-43, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36181861

RESUMO

The frozen semen of Erhualian pig can promote the continuous improvement of commercial pigs, but currently, frozen semen fails to satisfy the practical application requirement. Oxidative damage is one of the crucial factors affecting the quality of frozen semen; besides, there are individual differences in boar sperm freezability. Based on the previous analysis of the proteomic differences of Erhualian boar sperm with different freezability, two differentially abundant proteins (DAPs) in boar sperm, albumin (ALB) and protein disulfide isomerase family A member 4 (PDIA4), were selected as the research objects in the current study. It is assumed that redox-related proteins ALB and PDIA4 can be used as markers to predict Erhualian boar sperm freezability. We cryopreserved the semen of 14 Erhualian boars. According to the difference of frozen semen quality, boars with good and poor freezability ejaculates (GFE and PFE, n = 3) were selected respectively. The relative contents of ALB and PDIA4 in GFE and PFE were analyzed by Western blot, and the localization patterns of ALB and PDIA4 in pre-frozen and frozen-thawed sperm were detected by immunofluorescence. The results showed that the abundances of ALB and PDIA4 in GFE were significantly higher than PFE, and there was a significant correlation between the relative contents of ALB and PDIA4 and frozen-thawed sperm quality parameters. Additionally, the freezing process had no effect on the localization patterns of ALB and PDIA4 in spermatozoa. In conclusion, these results suggest that ALB and PDIA4 are related to boar sperm cryotolerance and may be used as novel freezability markers.


Assuntos
Análise do Sêmen , Preservação do Sêmen , Suínos , Animais , Masculino , Criopreservação/métodos , Isomerases de Dissulfetos de Proteínas/metabolismo , Proteômica , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Espermatozoides/metabolismo , Albuminas , Motilidade dos Espermatozoides
14.
Anim Genet ; 53(6): 897-900, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36086871

RESUMO

Tail type is an important trait that influences meat quality and consumer purchasing attitudes. As a novel genetic marker, the study of genomic copy number variations (CNVs) provides a new research method to study the genetic mechanisms underlying trait formation. In the present paper, we conducted CNV-based association studies for sheep tail type and growth traits in Hulunbuir sheep. A total of 167 CNVs and 288 individuals were analyzed at the marker and individual level, respectively. Association studies of 10 traits were carried out using two mixed linear models. We found that three, one and one CNV loci were significantly associated with tail type, tail length and tail fat weight, respectively, which together contained a total of 52 candidate genes. Out of these genes, five have been documented to be associated with fat metabolism in sheep. Our findings provide a reference for further studies on fat deposition in sheep as well as a theoretical basis for breeding Hulunbuir sheep with the required tail type.


Assuntos
Variações do Número de Cópias de DNA , Ovinos , Cauda , Animais , Variações do Número de Cópias de DNA/genética , Fenótipo , Ovinos/genética , Cruzamento
15.
Ophthalmic Res ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36436501

RESUMO

BACKGROUND: Due to its progressive nature, early evaluation and timely prediction of legal blindness are important in patients with neovascular age-related macular degeneration (nAMD). We examined the association between early-stage variation in central retinal thickness (CRT) and long-term visual outcomes in patients with nAMD. METHODS: We included 103 nAMD patients who were administered anti-vascular endothelial growth factor (anti-VGEF). Participants were considered qualified if they were: 1) 50 years and older, 2) treatment-naïve, 3) received standard anti-VEGF treatment and had complete baseline information. We further excluded patients with less than one-year follow-up data and those who experienced best-corrected visual acuity (BCVA) ≤35. Early-stage variability in CRT was measured as the first-year coefficient of variability (CV) of CRT. Patients were then classified into the high-variability and the low-variability groups according to the X-tile. A product-limit plot was used to demonstrate the differences and tested with the log-rank test. The association between first-year variability and visual outcomes was quantified using Cox regression models. Time-to-event primary endpoint was the overall visual preservation (OVP) rate, defined as the time from the first injection to legal blindness, i.e., BCVA ≤ 35 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. RESULTS: A threshold of 20% of first-year CV in CRT was used to categorized 76 qualified patients into high-variability (35, 46.1%) and low-variability (41, 53.9%). The 5- and 10-year OVPs for patients with high- vs. low-variability were 76% vs. 48%, and 59% vs. 22%, respectively. High early-stage CRT variability showed a significantly higher risk of legal blindness. Even after adjusting for the demographic and clinical features, the variability remained significant (HR=2.39, 95% CI: 1.20 to 4.78). CONCLUSIONS: First-year variability of CRT was predictive of long-term visual outcomes in patients with nAMD, and 20% of the variability could be used as a clinically convenient threshold to qualitatively classify patients into high- and low-variability groups. The current study is important for identifying high-risk populations and for long-term disease management.

16.
Water Sci Technol ; 86(5): 1193-1206, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36358055

RESUMO

Considering the urgent need for the analysis of trace-level pollutants in water samples, the pre-concentration of micropollutants in water samples has been the focus of extensive research. Among current pretreatment methods, the solid phase extraction (SPE) technique has received enormous attention because of its low cost, ease of operation and high efficiency. In this work, a new adsorbent (Fe3O4@Au@DTC NPs) was acquired through modification of Fe3O4 nanoparticles (NPs) with gold (Au) and dithiocarbamate (DTC). To investigate their application ability, the adsorbent were utilized as an SPE adsorbent to enrich polycyclic aromatic hydrocarbons in water (PAHs, fluoranthene, pyrene, benzo anthracene, benzo fluoranthene, benzo pyrene). The obtained Fe3O4@Au@DTC NPs were confirmed by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), and UV-Vis spectrum. Under optimal conditions, the calibration curves were obtained in the range of 10-500 ng L-1, while the limit of detection (LOD) ranged in 1.17-2.31 ng L-1. Furthermore, 50 mg of Fe3O4@Au@DTC NPs could extract trace PAHs from 500 mL real water samples into 1 mL eluent, and the spiked recoveries of five PAHs in river water and tap water reached 72-106% with relative standard deviations varying between 3.3-5.18%. Through the conversion of amines into DTC, we acquire desiring group modified Fe3O4 NPs, which showed great prospects in magnetic solid-phase extraction sphere and environmental field.


Assuntos
Nanopartículas de Magnetita , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Nanopartículas de Magnetita/química , Poluentes Químicos da Água/análise , Extração em Fase Sólida/métodos , Limite de Detecção , Água , Pirenos/análise
17.
Appl Microbiol Biotechnol ; 105(24): 9403-9418, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34837124

RESUMO

Phosphorus (P) accumulation in croplands resulting from ever-increasing input of P fertilizer strongly influences soil microbial growth and activities, which is expected to alter the soil priming effect (PE) induced by plant residue. However, the effect of P availability on the magnitude and direction of PE remains largely unexplored and the underlying microbial mechanisms are still unclear. Therefore, a 40-day incubation experiment was established by adding C4-maize straw to C3-soils with or without long-term P fertilizer inputs to investigate PE and accompanied dynamics of microbiota. The results revealed that in both soils, straw application caused positive real PEs via a "microbial co-metabolism" mechanism, accompanied by a microbial succession from the dominance of r- and K-strategists to K-strategists (mainly fungi). In addition, long-term amendment with P increased PE by 83.2% compared with no P fertilization control, which was mainly mediated by K-strategists, especially the fungal families Chaetomiaceae and Myrmecridiaceae. The increased PE was accompanied by enhanced microbial biomass carbon, extracellular enzyme activities, and bacterial gene abundance, confirming the "stoichiometric decomposition" theory. Meanwhile, deviating from the conventional paradigm, higher phosphatase activity and lower enzymatic stoichiometry of carbon (C)-to-P ratios in high-P soil compared with that in low-P soil suggested stronger "P mining" with high-P availability.


Assuntos
Microbiologia do Solo , Solo , Carbono , Produtos Agrícolas , Fertilizantes , Fungos , Humanos , Nitrogênio/análise
18.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430468

RESUMO

Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.


Assuntos
Diabetes Mellitus Tipo 2/genética , Intolerância à Glucose/genética , Glucose/genética , MicroRNAs/genética , Animais , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Glicólise/genética , Humanos , Camundongos , Camundongos Knockout , Família Multigênica/genética , NAD/metabolismo , Taxa Respiratória/genética , Transdução de Sinais/genética
19.
Phys Chem Chem Phys ; 22(28): 16236-16243, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32643728

RESUMO

Two-dimensional boron structures, due to their diverse properties, have attracted great attention because of their potential applications in nanoelectronic devices. A series of TiBn (2 ≤ n ≤ 13) monolayers are efficiently constructed through our motif based method and theoretically investigated through high-throughput first-principles calculations. The configurations are generated based on the motifs of boron dimeric/triangular/quadrilateral fragments and multi-coordinate titanium-centered boron molecular wheels. Besides previously reported TiB4 and TiB9 which were discovered by the global search method, we predict that high symmetry monolayer TiB7 (Cmmm), which is octa-coordinate titanium boride, is dynamically stable. The TiB7 monolayer is a BCS superconductor with a transition temperature Tc of up to 8.3 K. The motif based approach is proved to be efficient in searching stable structures with prior knowledge so that the potentially stable transition metal monolayers can be quickly constructed by using basic cluster motifs. As an efficient way of discovering materials, the method is easily extended to predict other types of materials which have common characteristic patterns in the structure.

20.
Sheng Li Xue Bao ; 72(4): 426-432, 2020 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-32820304

RESUMO

The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by ß-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.


Assuntos
Apoptose , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteínas de Ciclo Celular , Sobrevivência Celular , Senescência Celular , Fatores de Transcrição Forkhead , Humanos , Fatores de Transcrição , Cordão Umbilical
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