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1.
Plant Cell ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524462

RESUMO

Protons (H+) in acidic soils arrest plant growth. However, the mechanisms by which plants optimize their biological processes to diminish the unfavorable effects of H+ stress remain largely unclear. Here, we showed that in the roots of Arabidopsis thaliana, the C2H2-type transcription factor STOP1 in the nucleus was enriched by low pH in a nitrate-independent manner, with the spatial expression pattern of NITRATE TRANSPORTER 1.1 (NRT1.1) established by low pH required the action of STOP1. Additionally, the nrt1.1 and stop1 mutants, as well as the nrt1.1 stop1 double mutant, had a similar hypersensitive phenotype to low pH, indicating that STOP1 and NRT1.1 function in the same pathway for H+ tolerance. Molecular assays revealed that STOP1 directly bound to the promoter of NRT1.1 to activate its transcription in response to low pH, thus upregulating its nitrate uptake. This action improved the nitrogen use efficiency (NUE) of plants and created a favorable rhizospheric pH for root growth by enhancing H+ depletion in the rhizosphere. Consequently, the constitutive expression of NRT1.1 in stop1 mutants abolished the hypersensitive phenotype to low pH. These results demonstrate that STOP1-NRT1.1 is a key module for plants to optimize NUE and ensure better plant growth in acidic media.

2.
BMC Ophthalmol ; 21(1): 336, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530754

RESUMO

BACKGROUND: There are few reports regarding the influence of varying illumination on the compensation effect before and after corneal refractive surgery. We aimed to evaluate the changes in refraction, higher-order aberrations, and aberration compensation between mesopic and photopic illumination before and after small incision lenticule extraction. METHODS: In this prospective cohort study, only the right eyes of patients who underwent small incision lenticule extraction for the correction of myopia and myopic astigmatism at the Tianjin Eye Hospital were included. Wavefront refraction and higher-order aberrations were measured preoperatively and 3 months postoperatively under mesopic and photopic illumination. Compensation factors were calculated as 1 - (aberration of the whole eye/aberration of the anterior corneal surface). RESULTS: Forty patients undergoing small incision lenticule extraction were enrolled. All surgeries were completed without postoperative complications. Preoperatively, the eyes only had a statistically significantly higher (t = - 4.589, p < .001) spherical refractive error under mesopic vs. photopic illumination (median [interquartile range], - 6.146 [2.356] vs. - 6.030 [2.619] diopters [D]), whereas postoperatively, the eyes also exhibited statistically significantly higher (t = - 3.013, p = .005) astigmatism (- 0.608 [0.414] vs. - 0.382 [0.319] D). Differences in spherical refraction between the two illuminations were the highest in postoperative eyes (Δ > 0.5 D). Only postoperative eyes exhibited statistically significant elevations (t ≥ 4.081, p < .001) in higher-order aberrations under mesopic illumination, and only preoperative eyes exhibited statistically significantly enhanced (χ2 = 6.373, p = .01 for fourth-order and χ2 = 11.850, p = .001 for primary spherical aberrations) and decreased (χ2 = 13.653, p = .001 for horizontal trefoil) compensation factors under mesopic illumination. CONCLUSIONS: Exaggerations in higher-order aberrations and myopic shift after small incision lenticule extraction became apparent under mesopic illumination. Slight undercorrection may have an enhanced effect under low illumination and may reduce night vision. The specific changes in compensation effects in preoperative eyes may improve optical quality under mesopic illumination. Postoperative eyes have reduced compensation ability, specifically for spherical aberrations, under mesopic illumination, which may diminish night vision. Further studies that include the measurement of subjective night vision parameters should be conducted.


Assuntos
Astigmatismo , Cirurgia da Córnea a Laser , Aberrações de Frente de Onda da Córnea , Astigmatismo/cirurgia , Substância Própria/cirurgia , Humanos , Lasers de Excimer/uso terapêutico , Iluminação , Estudos Prospectivos , Refração Ocular , Acuidade Visual
3.
JAMA Netw Open ; 4(9): e2125544, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533568

RESUMO

Importance: Early identification and intervention for newborns with hearing loss (HL) may lead to improved physiological and social-emotional outcomes. The current newborn hearing screening is generally beneficial but improvements can be made. Objective: To assess feasibility and evaluate utility of a modified genetic and hearing screening program for newborn infants. Design, Setting, and Participants: This population-based cohort study used a 4-stage genetic and hearing screening program at 6 local hospitals in Nantong city, China. Participants were newborn infants born between January 2016 and June 2020 from the Han population. Statistical analysis was performed from April 1 to May 1, 2021. Exposures: Limited genetic screening for 15 variants in 4 common HL-associated genes and newborn hearing screening (NHS) were offered concurrently to all newborns. Hearing rescreening and/or diagnostic tests were provided for infants with evidence of HL on NHS or genetic variants on screening. Expanded genetic tests for a broader range of genes were targeted to infants with HL with negative results of limited genetic tests. Main Outcomes and Measures: The detection capability for infants with hearing impairment who passed conventional hearing screening, as well as infants with normal hearing at risk of late-onset HL due to genetic susceptibility. Results: Among a total of 35 930 infants, 32 512 infants completed the follow-up and were included for analysis. Among the infants included in the analysis, all were from the Han population in China and 52.3% (16 988) were male. The modified genetic and hearing screening program revealed 142 cases of HL and 1299 cases of genetic variation. The limited genetic screening helped identify 31 infants who passed newborn hearing screening, reducing time for diagnosis and intervention; 425 infants with normal hearing with pathogenic SLC26A4 variation and 92 infants with MT-RNR1 variation were at risk for enlarged vestibular aqueduct and aminoglycoside-induced ototoxicity respectively, indicating early aversive or preventive management. Conclusions and Relevance: This study found that performing modified genetic and hearing screening in newborns was feasible and provides evidence that the program could identify additional subgroups of infants who need early intervention. These findings suggest an advantage for universal adoption of such a practice.

4.
Blood Adv ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521107

RESUMO

Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. The clinical trial (ChiCTR1800014457) examined the feasibility of sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response sequentially underwent one or more additional infusions of CAR T-cell targeting CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to cutoff date was 17 months (range, 15 to 23). The estimated 18-month complete response rate was 78% (95% confidence interval [CI], 54 to 91). The estimated 18-month progression-free survival rate was 78% (95% CI, 55 to 90), with 78% (95% CI, 37 to 94) in patients with bulky diseases and 60% (95% CI, 25 to 83) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity occurred in 34.8% and 21.7% of all patients, respectively. During subsequent infusions, few incidences of higher than grade 2 CRS and neurotoxicity were observed. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS and non-CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric refractory/relapsed Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as ChiCTR1800014457.

5.
Brain Imaging Behav ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34535879

RESUMO

The aim of this study was to investigate the abnormities in functional connectivity (FC) within each modular network and between modular networks in patients with systemic lupus erythematosus (SLE). Twelve meaningful modular networks were identified via independent component analysis from 41 patients and 40 volunteers. Parametric tests were used to compare the intra- and intermodular FC between the groups. Partial correlation analysis was used to seek the relationships between abnormal FCs and the clinical data. Compared to the controls, SLE patients showed decreased intramodular FC in the anterior default mode network (aDMN), posterior default mode network (pDMN), ventral attention network (VAN), and sensorimotor network (SMN) and increased intramodular FC in the medial visual network (mVN) and left frontoparietal network. In addition, SLE patients showed decreased intermodular FC between the SMN and the lateral visual network (lVN), between the SMN and the VAN, and between the pDMN and the lVN and exhibited increased intermodular FC between the SMN and the salience network (SAN), between the pDMN and the SAN, and between the aDMN and the VAN. Moreover, we found several correlations among the abnormal FCs and the Mini-Mental State Examination in SLE patients. Mild cognitive impairment is compensated by the hyperconnectivity between the aDMN and the VAN, while severe cognitive impairment tends to be compensated by the hyperconnectivity between the SMN and the SAN. The FC value between the SMN and the SAN and between the aDMN and the VAN may serve as neuroimaging markers for monitoring cognitive progression in SLE patients.

6.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490478

RESUMO

Age­related macular degeneration (AMD) is a global health problem. Lycium barbarum polysaccharide (LBP), a traditional Chinese herbal medicine, has been proven to be effective against several eye diseases. However, only a few studies have investigated the effectiveness of LBP for AMD. In the present study, the human retinal epithelial cell line, ARPE­19, was pretreated with LBP for 24 h before exposure to H2O2 (500 µM). Cell viability was assessed, and a series of oxidative and antioxidant indicators were evaluated to determine the influence of LBP on H2O2­triggered oxidative stress. The present study also determined the apoptosis status, as well as the expression levels of apoptotic proteins and nuclear factor erythroid 2­related factor 2 (Nrf2)/heme oxygenase­1 (HO­1) pathway proteins. The present study aimed to determine the protective role for LBP pretreatment and its underlying molecular mechanism. The results of the present study suggest that pretreatment of ARPE­19 cells with LBP exhibit high efficacy at reducing oxidative damage and inhibiting cell apoptosis. Furthermore, LBP may modulate the expression of proteins involved in the apoptotic pathway and activate the Nrf2 signaling pathway.

7.
Redox Rep ; 26(1): 170-175, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34530696

RESUMO

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear.Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice.Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined.Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis.Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.

8.
Photodiagnosis Photodyn Ther ; 36: 102487, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411738

RESUMO

INTRODUCTION: Delineating the margins of Oral squamous cell carcinoma (OSCC) is a critical step for optimaltumor resection. The aim of this study was to evaluate the accuracy of lesion surgical margin identification using autofluorescence visualization. MATERIALS AND METHODS: Thirty patients with OSCC were included in this study. For each lesion, the fluorescence loss boundary was determined using VELscope before ablative surgical resection (with a 1.5-2cm safety margin) was performed. A total of 126 samples were obtained from 30 surgical specimens, each containing the tissue from the fluorescence loss boundary to surgical margin. The status of each sample was determined by oral pathologists and the staining intensities of Ki-67, E-cadherin, and Vimentin at the fluorescence loss boundary and surgical margin were evaluated by immunohistochemistry. RESULTS: Fluorescence loss regions were identified in all patients. Of the 126 samples collected, HE staining identified 77 normal epithelia (61.1%), 26 mild dysplasia (20.6%), 17 severe dysplasia (13.4%) and 6 carcinomas in situ (4.9%). A significant correlation was found between the differentiation grade of tumor cells and the pathological status of the surgical marginal specimens (P<0.05). Forty-two of the 126 samples were randomly selected for further immunohistochemical staining. No significant differences were seen in Ki-67, E-cadherin, or Vimentin expression at the fluorescence loss boundary or surgical margin, however, the proteins' expression level was positively correlated with the degree of dysplasia (P<0.01). CONCLUSION: Autofluorescence visualization has potential as a simple surgical margin setting device for OSCC and may help delineate the superficial area of OSCC with acceptable accuracy. However, when considering the inherent limitations of this system, we suggest that the approach should only be applied under certain conditions, such as when dealing with superficial, well-differentiated lesions.

9.
Mol Plant ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34364002

RESUMO

Nucleotide-binding leucine-rich repeat (NLR) genes comprise the largest family of plant disease resistance genes. Angiosperm NLR genes are phylogenetically divided into the TNL, CNL, and RNL subclasses. NLR copy numbers and subclass composition vary tremendously across angiosperm genomes. However, the evolutionary associations between genomic NLR content and ecological adaptation, or between NLR content and signal transduction components, are poorly characterized due to limited genome availability. Here, we established an angiosperm NLR atlas (ANNA, https://biobigdata.nju.edu.cn/ANNA/), which includes NLR genes from over 300 angiosperm genomes. Using ANNA, we revealed that NLR copy numbers differ up to 66-fold among closely related species due to rapid gene loss and gain. Interestingly, NLR contraction was associated with adaptations to aquatic, parasitic, and carnivorous lifestyles. The convergent NLR reduction in aquatic plants resembles the lack of NLR expansion during the long-term evolution of green algae before the colonization of land. A co-evolutionary pattern between NLR subclasses and plant immune-pathway components was also identified, suggesting that immune pathway deficiencies may drive TNL loss. Finally, we recovered a conserved TNL lineage that may function independently of the EDS1-SAG101-NRG1 module. Our findings provide new insights into the evolution of NLR genes in the context of ecological adaptation and genome content variation.

10.
Talanta ; 234: 122621, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364430

RESUMO

Altered H2S levels and intracellular viscosity have both been seen in Parkinson's disease (PD). However, how H2S and intracellular viscosity are involved in PD pathogenesis remains unknown. Herein, a dual-function fluorescent probe DF was designed and synthesized to analyze intracellular viscosity and hydrogen sulfide. It is a near-infrared fluorescence probe with improved photostability and large Stokes shift (110 nm). The probe reveals increased viscosity and hydrogen sulfide in zebrafish model of PD for the first time.


Assuntos
Sulfeto de Hidrogênio , Doença de Parkinson , Animais , Corantes Fluorescentes , Células HeLa , Humanos , Viscosidade , Peixe-Zebra
11.
Artigo em Inglês | MEDLINE | ID: mdl-34444628

RESUMO

Coastal blue carbon storage (CBCS) plays a key role in addressing global climate change and realizing regional carbon neutrality. Although blue carbon has been studied for some years, there is little understanding of the influence of a megacity's complex natural and human-driven processes on CBCS. Taking the Shanghai coastal area as an example, this study investigated the spatiotemporal change in CBCS using the InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) model during 1990-2015, and analyzed the response of the CBCS to a megacity's complex natural- and human-driven processes through a land use/land cover transition matrix and hierarchical clustering. The results were as follows: (1) Thirty-three driving processes were identified in the study area, including four natural processes (e.g., accretion, succession, erosion, etc.), two human processes (reclamation and restoration) and twenty-seven natural-human coupled processes; they were further combined into single and multiple processes with positive and negative influences on the CBCS into four types (Mono+, Mono-, Multiple+ and Multiple- driving processes). (2) Shanghai's CBCS increased from 1659.44 × 104 Mg to 1789.78 ×104 Mg, though the amount of Shanghai's coastal carbon sequestration showed a decreasing trend in three periods: 51.28 × 104 Mg in 1990-2000, 42.90 × 104 Mg in 2000-2009 and 36.15 × 104 Mg in 2009-2015, respectively. (3) There were three kinds of spatiotemporal patterns in the CBCS of this study area: high adjacent to the territorial land, low adjacent to the offshore waters in 1990; high in the central part, low in the peripheral areas in 2009 and 2015; and a mixed pattern in 2000. These patterns resulted from the different driving processes present in the different years. This study could serve as a blueprint for restoring and maintaining the CBCS of a megacity, to help mitigate the conflicts between socioeconomic development and the conservation of the CBCS, especially in the Shanghai coastal area.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Carbono , Sequestro de Carbono , China , Humanos
12.
Ecotoxicol Environ Saf ; 224: 112706, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34461317

RESUMO

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

13.
BMJ Case Rep ; 14(8)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433537

RESUMO

A 40-year-old Chinese woman presented with a 4-year history of lower back pain and left lower leg sciatica. The patient had previously tried different modalities of treatments, including massage, acupuncture, ultrasound, alternative Bowen therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), all of which only provided temporary relief. On presentation to a tertiary hospital, careful and comprehensive history taking found that the sciatica pattern of pain always coincided with menstruation. An MRI identified a thickened left sciatic nerve, with surgery confirming sciatic nerve endometriosis. The case highlights the importance of comprehensive history taking in accurately diagnosing a rare aetiology of sciatica with subsequent prompt surgical intervention to avoid severe disability as well as follow-up treatment to prevent recurrence.


Assuntos
Endometriose , Ciática , Espondilose , Adulto , China , Endometriose/complicações , Endometriose/diagnóstico , Feminino , Humanos , Nervo Isquiático , Ciática/diagnóstico , Ciática/etiologia
14.
J Ethnopharmacol ; 281: 114504, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34371116

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: The Euphorbiaceae family, which contains about 300 genera and more than 5000 species, is widely distributed in different regions. Trigonostemon genus comprises a wide group of tropical and temperate plants belonging to the Euphorbiaceae family. This genus includes at least 50 species throughout tropical Asia, extending from India and Sri Lanka to New Guinea. They have been employed by local populations for the treatment of asthma, poisonous snake bites, and food poisoning. AIM OF THE REVIEW: The main aim of the review is to critically analyze the reported traditional uses, bioactive chemical constituents and pharmacological activities of Trigonostemon species. MATERIALS AND METHODS: Scientific databases, including Google Scholar, PubMed, CNKI, SpringerLink, Web of Science, Wiley Online Library and SciFinder, were searched using keywords such as "Trigonostemon", "South China", "chemical constituents", or "traditional use". Thus, available articles from 2000 to 2020 were collected and analyzed. RESULTS AND DISCUSSION: This paper provides systematic data that Trigonostemon species possess a diverse phytochemical composition, (including diterpenes, alkaloids, coumarins, lignins, sesquiterpenes, triterpenoids, flavonoids, and polyphenols) found in different plant organs. Research on Trigonostemon plants has revealed critical therapeutic properties, such as antiviral, anti-tumor, antimicrobial, anti-inflammatory, and insecticidal activities. CONCLUSIONS: It is envisaged that the current review will add value to more scientific research on Trigonostemon species and enhance/promote the increased interest in the sustainable use of Trigonostemon species as well as lead to the validation of unverified ethnobotanical claims. Future studies on Trigonostemon species would focus on establishing the links between the traditional uses, active compounds and reported pharmacological activities.

15.
Signal Transduct Target Ther ; 6(1): 299, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373448

RESUMO

Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma (HCC) in individuals infected with the hepatitis virus. However, the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined. Here, we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1 (AFB1) targets. Among the most significant hits was the aryl hydrocarbon receptor (AHR), a ligand-binding transcription factor regulating cell metabolism, differentiation, and immunity. AHR-deficient cells tolerated high concentrations of AFB1, in which AFB1 adduct formation was significantly decreased. AFB1 triggered AHR nuclear translocation by directly binding to its N-terminus. Furthermore, AHR mediated the expression of P450 induced by AFB1. AHR expression was also elevated in primary tumor sections obtained from AFB1-HCC patients, which paralleled the upregulation of PD-L1, a clinically relevant immune regulator. Finally, anti-PD-L1 therapy exhibited greater efficacy in HCC xenografts derived from cells with ectopic expression of AHR. These results demonstrated that AHR was required for the AFB1 toxicity associated with HCC, and implicate the immunosuppressive regimen of anti-PD-L1 as a therapeutic option for the treatment of AFB1-associated HCCs.

16.
Sci Total Environ ; 798: 149285, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34340090

RESUMO

Identifying the genes that affect cadmium (Cd) accumulation in plants is a prerequisite for minimizing dietary Cd uptake from contaminated edible parts of plants by genetic engineering. This study showed that Cd stress inhibited the expression of FERONIA (FER) gene in the roots of wild-type Arabidopsis. Knockout of FER in fer-4 mutants downregulated the Cd-induced expression of several genes related to iron (Fe) uptake, including IRT1, bHLH38, NRAMP1, NRAMP3, FRO2 andFIT. In addition, the Cd concentration in fer-4 mutant roots reduced to approximately half of that in the wild-type seedlings. As a result, the Cd tolerance of fer-4 was higher. Furthermore, increased Fe supplementation had little effect on the Cd tolerance of fer-4 mutants, but clearly improved the Cd tolerance of wild-type seedlings, showing that the alleviation of Cd toxicity by Fe depends on the action of FER. Taken together, the findings demonstrate that the knockout of FER might provide a strategy to reduce Cd contamination and improve the Cd tolerance in plants by regulating the pathways related to Fe uptake.

17.
J Immunol Res ; 2021: 7223500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395634

RESUMO

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin (n = 15; control group) and tissues at tumor centers from patients with cheek BCC (n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the "basal cell carcinoma pathways" were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

18.
Insect Biochem Mol Biol ; 137: 103625, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34358664

RESUMO

Scorpion α-toxins bind at the pharmacologically-defined site-3 on the sodium channel and inhibit channel inactivation by preventing the outward movement of the voltage sensor in domain IV (IVS4), whereas scorpion ß-toxins bind at site-4 on the sodium channel and enhance channel activation by trapping the voltage sensor of domain II (IIS4) in its outward position. However, limited information is available on the role of the voltage-sensing modules (VSM, comprising S1-S4) of domains I and III in toxin actions. We have previously shown that charge reversing substitutions of the innermost positively-charged residues in IIIS4 (R4E, R5E) increase the activity of an insect-selective site-4 scorpion toxin, Lqh-dprIT3-c, on BgNav1-1a, a cockroach sodium channel. Here we show that substitutions R4E and R5E in IIIS4 also increase the activity of two site-3 toxins, LqhαIT from Leiurusquinquestriatus hebraeus and insect-selective Av3 from Anemonia viridis. Furthermore, charge reversal of either of two conserved negatively-charged residues, D1K and E2K, in IIIS2 also increase the action of the site-3 and site-4 toxins. Homology modeling suggests that S2-D1 and S2-E2 interact with S4-R4 and S4-R5 in the VSM of domain III (III-VSM), respectively, in the activated state of the channel. However, charge swapping between S2-D1 and S4-R4 had no compensatory effects on gating or toxin actions, suggesting that charged residue interactions are complex. Collectively, our results highlight the involvement of III-VSM in the actions of both site 3 and site 4 toxins, suggesting that charge reversing substitutions in III-VSM allosterically facilitate IIS4 or IVS4 voltage sensor trapping by these toxins.

19.
Ann Palliat Med ; 10(7): 7236-7246, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263625

RESUMO

BACKGROUND: Acute ischemic stroke (AIS) is the major type of stroke, which highly risks human health and life quality. Governor vessel acupuncture (GV Ac) is one specific acupoint selection treatment. This study aimed to systematically evaluate the clinical value of GV Ac in AIS patients. METHODS: Seven electronic databases were searched for all related randomized controlled trials before December 2020. The included studies should meet the following criteria: all target patients were diagnosed as AIS; the experimental group used GV Ac as the only intervention or combined with routine neurology therapy as conventional treatment; the control group received ordinary acupuncture, or the same conventional treatment as the experimental group, or both. Evaluated the quality of all included trials and performed a meta-analysis of the extracted data. RESULTS: A total of 18 trials were included, involving 1,543 AIS patients. The results showed compared to the conventional treatment, GV Ac combining with conventional therapy resulted in Barthel Index (BI) (MD =14.16, 95% CI: 7.34, 20.79) improvement, mRS (MD =-0.63, 95% CI: -0.95, -0.32, P<0.0001) decrease, better National Institute of Health Stroke Scale (NIHSS) scores (MD =-1.18, 95% CI: -1.52, -0.83), and lower China Stroke Score (CSS)/Modified Edinburgh-Scandinavia Stroke Scale (MESSS) scores (MD =-3.77, 95% CI: -4.98, -2.57). Furthermore, GV Ac could better improve activities of daily living (ADL) (MD =8.27, 95% CI: 4.29, 12.26) and neurological deficit scores (NIHSS: MD =-1.32, 95% CI: -2.18, -0.47; CSS/MESSS: MD =-4.63, 95% CI: -5.91, -3.35), when compared to the ordinary acupuncture. DISCUSSION: According to the current evidence, GV Ac for AIS's efficacy appears to be better than that of ordinary acupuncture. When combined with conventional treatment, GV Ac may increase the benefit. But limited by the methodological quality of the included studies, more strictly designed large-scale randomized controlled trials are needed. TRIAL REGISTRATION NUMBER: CRD42020203480.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Atividades Cotidianas , Isquemia Encefálica/terapia , Humanos , Acidente Vascular Cerebral/terapia
20.
Anim Biotechnol ; : 1-12, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236285

RESUMO

Skeletal muscle also plays a vital role in regulating the movement energy storage and health of metabolism. In order to investigate the expression profile of protein and phosphor-proteins in chicken skeletal muscle during embryonic development, we performed phosphor-proteomics analysis by label-free and TiO2 enrichment strategy in chicken leg muscle tissues of at embryonic age embryo day 7(E7), E12, E17 and 3-day post-hatch (D3). The study led to the identification of 4332 proteins in the proteome and 1043 phosphorylation modification sites in the phosphorylated proteome, corresponding to 718 proteins (FC ≥ 2 or FC ≤ 0.5 and p < 0.05). The DEP-associated biological processes were involved in Focal adhesion, Glycolysis/gluconeogenesis, Arginine and proline metabolism by KEGG analysis. PPI analyses revealed that these DEPs TNNC1, TNNC2, TNNT2, TNNT3 and phosphorylated DEPs MYLPF interacted with involved pathways. Integrative analysis of proteome and phosphoproteome data found 324 common proteins, corresponding to 521 modification sites and Focal adhesion was the only pathway significantly enriched. These results provide a basis for further understanding the proteome and phosphoproteome and their regulatory biochemical pathways during the development of embryonic chicken skeletal muscle.

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