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1.
Plant Sci ; 312: 111058, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620452

RESUMO

Uptake and internal transport of micronutrients are essential for plant growth, development, and yield. In this regard, Iron Regulated Transporters (IRTs) from the Zinc Regulated Transporter (ZRT)/IRT-related protein (ZIP) family play an important role in transition metal uptake. Most studies have been focused on IRT1-like proteins in diploid species. Information on IRT1-like proteins in polyploids is limited. Here, we studied the function of TpIRT1A and TpIRT1B homoeologs in a tetraploid crop, Polish wheat (Triticum polonicum L.). Our results highlighted the importance of TpIRT1 in mediating the uptake and translocation of Fe, Mn, Co, and Cd with direct implications for wheat yield potential. Both TpIRT1A and TpIRT1B were located at the plasma membrane and internal vesicle-like organelle in protoplasts of Arabidopsis thaliana L. and increased Cd and Co sensitivity in yeast. The over-expression of TpIRT1B in A. thaliana increased Fe, Mn, Co, and Cd concentration in its tissues and improved plant growth under Fe, Mn, and Co deficiencies, while increased the sensitivity to Cd compared to wild type. Functional analysis of IRT1 homoeologs from tetraploid and diploid ancestral wheat species in yeast disclosed four distinct amino acid residues in TdiIRT1B (T. dicoccum L. (Schrank)) and TtuIRT1B (T. turgidum L.). Together, our results increase the knowledge of IRT1 function in a globally important crop, wheat.

2.
J Alzheimers Dis ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34602486

RESUMO

BACKGROUND: Amyloid plaques and neurofibrillary tangles are two pathological hallmarks of Alzheimer's disease (AD). However, synaptic deficits occur much earlier and correlate stronger with cognitive decline than amyloid plaques and neurofibrillary tangles. Mislocalization of tau is an early hallmark of neurodegeneration and precedes aggregations. Sirtuin type 1 (SIRT1) is a deacetylase which acts on proteins including transcriptional factors and associates closely with AD. OBJECTIVE: The present study investigated the association between SIRT1 and tau expression in cells and in mice brains. METHODS: Western blot was performed to detected tau, SIRT1, C/EBPα, and GAPDH protein levels. Immunological fluorescence assay was used to assess tau localization in primary cortical neuronal cells. Golgi staining was performed to evaluated dendritic spine morphology in mice brains. RESULTS: In the present study, we found that SIRT1 negatively regulates expression of tau at the transcriptional level through transcriptional factor C/EBPα. Inhibition of the activity of SIRT1 limits the distribution of tau to the neurites. In the meantime, the alteration of dendritic spine morphology is also observed in the brains of SIRT1+/- mice. CONCLUSION: SIRT1 may be a potential drug target for early intervention in AD.

4.
J Neurooncol ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599481

RESUMO

INTRODUCTION: Many patients with glioma experience surgery-related language impairment. This study developed a classification system to predict postoperative language prognosis. METHODS: Sixty-eight patients were retrospectively reviewed. Based on their location, tumors were subtyped as follows: (I) inferior frontal lobe or precentral gyrus; (II) posterior central gyrus or supramarginal gyrus (above the lateral fissure level); (III) posterior region of the superior or middle temporal gyri or supramarginal gyrus (below the lateral fissure level); and (IV) insular lobe. The distance from the tumor to the superior longitudinal fasciculus/arcuate fasciculus was calculated. The recovery of language function was assessed using the Western Aphasia Battery before surgery, and a comprehensive language test was conducted on the day of surgery; 3, 7, and 14 days after surgery. Our follow-up information of was the comprehensive language test from telephone interviews in 3 months after surgery. RESULTS: Thirty-three patients experienced transient language impairment within 1 week of surgery. Fourteen patients had permanent language impairment. Type II tumors, shorter distance from the tumor to the posterior superior longitudinal fasciculus/arcuate fasciculus, and isocitrate dehydrogenase mutations were risk factors for surgery-related language impairment. Regarding the presence or absence of permanent surgery-related language impairments, the cut-off distance between the tumor and posterior superior longitudinal fasciculus/arcuate fasciculus was 2.75 mm. CONCLUSIONS: According to our classification, patients with type II tumors had the worst language prognosis and longest recovery time. Our classification, based on tumor location, can reliably predict postoperative language status and may be used to guide tumor resection.

5.
BMC Anesthesiol ; 21(1): 233, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583650

RESUMO

BACKGROUND AND OBJECTIVES: Peripheral injection of dexmedetomidine (DEX) has been widely used in regional anesthesia to prolong the duration of analgesia. However, the optimal perineural dose of DEX is still uncertain. It is important to elucidate this characteristic because DEX may cause dose-dependent complications. The aim of this meta-analysis was to determine the optimal dose of perineural DEX for prolonged analgesia after brachial plexus block (BPB) in adult patients undergoing upper limb surgery. METHOD: A search strategy was created to identify suitable randomized clinical trials (RCTs) in Embase, PubMed and The Cochrane Library from inception date to Jan, 2021. All adult patients undergoing upper limb surgery under BPB were eligible. The RCTs comparing DEX as an adjuvant to local anesthetic (LA) with LA alone for BPB were included. The primary outcome was duration of analgesia for perineural DEX. Secondary outcomes included visual analog scale (VAS) in 12 and 24 h, consumption of analgesics in 24 h, and adverse events. RESULTS: Fifty-seven RCTs, including 3332 patients, were identified. The subgroup analyses and regression analyses revealed that perineural DEX dose of 30-50 µg is an appropriate dosage. With short-/intermediate-acting LAs, the mean difference (95% confidence interval [CI]) of analgesia duration with less than and more than 60 µg doses was 220.31 (153.13-287.48) minutes and 68.01 (36.37-99.66) minutes, respectively. With long-acting LAs, the mean differences (95% CI) with less than and more than 60 µg doses were 332.45 (288.43-376.48) minutes and 284.85 (220.31-349.39) minutes. CONCLUSION: 30-50 µg DEX as adjuvant can provides a longer analgesic time compared to LA alone and it did not increase the risk of bradycardia and hypotension.

6.
Chin Med J (Engl) ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34561323

RESUMO

ABSTRACT: The demand for acquiring different languages has increased with increasing globalization. However, knowledge of the modification of the new language in the neural language network remains insufficient. Although many details of language function have been detected based on the awake intra-operative mapping results, the language neural network of the bilingual or multilingual remains unclear, which raises difficulties in clinical practice to preserve patients' full language ability in neurosurgery. In this review, we present a summary of the current findings regarding the structure of the language network and its evolution as the number of acquired languages increased in glioma patients. We then discuss a new insight into the awake intra-operative mapping protocol to reduce surgical risks during the preservation of language function in multilingual patients with glioma.

7.
Int J Nurs Pract ; : e13014, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34515390

RESUMO

PURPOSE: This study aimed to determine the moderating effect of work-related social support on the relationship between work-family-school role conflicts and job satisfaction among female registered nurses pursuing further degrees in China. METHODS: The study had a cross-sectional correlational design. Convenience sampling was applied to recruit participants from eight hospitals in China from January to August 2017. SPSS software and the PROCESS macro were used to conduct the data analyses in the present study. RESULTS: A total of 320 nurses were included in the present study. Work-family-school role conflicts were negatively correlated with job satisfaction (r = -0.21, P < 0.001). Work-related social support was a significant moderator (interaction effect: ß = 0.22, P = 0.039) on the relationship between work-family-school role conflicts and job satisfaction. CONCLUSIONS: The study revealed that when nurses perceived that they received a low or moderate level of social support in the workplace that strengthened the relationship between work-family-school role conflicts and job satisfaction. Hospital administrators should implement school- and family-friendly policies that increase the social support provided to nurses pursuing further degrees to balance their responsibilities of work, family and school and to improve their job satisfaction.

8.
J Pak Med Assoc ; 71(7): 1856-1861, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34410261

RESUMO

Exosomes are 20-150nm cell secreting nano-bodies that helps in the transportation of various biomolecules, including micro ribonucleic acid (miRNA) in the human body during both normal and diseased conditions. The current review was planned to summarise the role of miRNA carried by circulatory exosomes in cancer. miRNA is responsible for contribution in cancer, regulation of gene expression, interfering in biological pathways, gene silencing or amplification, and also has a role in cancer resistance. (miRNA) plays a dynamic role in this process by regulating the genes related to drug resistance, cell proliferation, cell cycle and apoptosis through a tissue-specific fashion. Owing to its significances, micro ribonucleic acid has been reported to be the key regulator of cancer, metastasis and also a factor in cancer resistance, and is a better source of possible potential diagnostic biomarkers. Though many studies have explored the biological roles of RNAs in cancer, many facts are needed to be investigated for clinical applications.


Assuntos
Exossomos , MicroRNAs , Neoplasias , Apoptose , Proliferação de Células , Exossomos/genética , Humanos , MicroRNAs/genética , Neoplasias/genética
9.
Langmuir ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342997

RESUMO

Photo-induced alignment of the thin-film morphologies of azobenzene-containing block copolymers (BCPs) is an effective method to obtain a uniaxial pattern of nanocylinders. Although film thickness is an important factor affecting the self-assembly of BCP thin films, the influence of film thickness on the photo-induced alignment of BCP thin-film morphology has never been systematically studied. Herein, we report the thickness-dependent photo-aligned film morphologies of the BCP containing an azobenzene-based liquid crystalline polymer and a poly(ionic liquid) (PIL), with a perfect uniaxial pattern of PIL nanocylinders. For films aligned with the unpolarized light (UPL), the out-of-plane PIL nanocylinders can be obtained in the film with a thickness of only 1L0 (∼30 nm, where L0 is the layer spacing of the hexagonally packed cylinder array), which is far lower than the thickness (more than 4L0) of the thermally annealed film needed to obtain the same morphology. This change is attributed to the orientation effect of UPL on azobenzene mesogens that suppresses the excluded volume effect. For the films aligned with linearly polarized light (LPL), to take advantage of the excluded volume effect to obtain the planar orientation of azobenzene mesogens, the thickness should be controlled to be no more than 3L0 to achieve an in-plane uniaxial alignment of PIL nanocylinders. The above relationship between the morphology and thickness of photo-aligned film eliminates the obstacles encountered in preparing films with well-ordered photo-aligned morphologies.

10.
Eur Radiol ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34417848

RESUMO

OBJECTIVES: The molecular subtyping of diffuse gliomas is important. The aim of this study was to establish predictive models based on preoperative multiparametric MRI. METHODS: A total of 1016 diffuse glioma patients were retrospectively collected from Beijing Tiantan Hospital. Patients were randomly divided into the training (n = 780) and validation (n = 236) sets. According to the 2016 WHO classification, diffuse gliomas can be classified into four binary classification tasks (tasks I-IV). Predictive models based on radiomics and deep convolutional neural network (DCNN) were developed respectively, and their performances were compared with receiver operating characteristic (ROC) curves. Additionally, the radiomics and DCNN features were visualized and compared with the t-distributed stochastic neighbor embedding technique and Spearman's correlation test. RESULTS: In the training set, areas under the curves (AUCs) of the DCNN models (ranging from 0.99 to 1.00) outperformed the radiomics models in all tasks, and the accuracies of the DCNN models (ranging from 0.90 to 0.94) outperformed the radiomics models in tasks I, II, and III. In the independent validation set, the accuracies of the DCNN models outperformed the radiomics models in all tasks (0.74-0.83), and the AUCs of the DCNN models (0.85-0.89) outperformed the radiomics models in tasks I, II, and III. DCNN features demonstrated more superior discriminative capability than the radiomics features in feature visualization analysis, and their general correlations were weak. CONCLUSIONS: Both the radiomics and DCNN models could preoperatively predict the molecular subtypes of diffuse gliomas, and the latter performed better in most circumstances. KEY POINTS: • The molecular subtypes of diffuse gliomas could be predicted with MRI. • Deep learning features tend to outperform radiomics features in large cohorts. • The correlation between the radiomics features and DCNN features was low.

11.
Environ Toxicol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432352

RESUMO

Microcystin-leucine-arginine (MC-LR) is a toxin secreted by freshwater cyanobacteria that is considered a potential environmental risk factor for Alzheimer's disease (AD). A previous study indicated that tau protein hyperphosphorylation via protein phosphatase 2A (PP2A) and GSK-3ß inhibition was the mechanism by which MC-LR induces neurotoxicity; however, how MC-LR-induced neurotoxicity can be effectively prevented remains unclear. In this study, the reversal effect of metformin on MC-LR-induced neurotoxicity was investigated. The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity. The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells. Metformin prevented spatial memory deficits in rats caused by intrahippocampal MC-LR administration. In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3ß activation.

12.
Nat Commun ; 12(1): 4876, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385436

RESUMO

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.


Assuntos
Técnicas Biossensoriais/instrumentação , Medicina de Precisão/instrumentação , Têxteis , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio/instrumentação , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/virologia , Desenho de Equipamento , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Medicina de Precisão/métodos , SARS-CoV-2/fisiologia , Suor/fisiologia
13.
Cytogenet Genome Res ; 161(3-4): 213-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34233333

RESUMO

The genera of the tribe Triticeae (family Poaceae), constituting many economically important plants with abundant genetic resources, carry genomes such as St, H, P, and Y. The genome symbol of Roegneria C. Koch (Triticeae) is StY. The St and Y genomes are crucial in Triticeae, and tetraploid StY species participate extensively in polyploid speciation. Characterization of St and Y nonhomologous chromosomes in StY-genome species could help understand variation in the chromosome structure and differentiation of StY-containing species. However, the high genetic affinity between St and Y genome and the deficiency of a complete set of StY nonhomologous probes limit the identification of St and Y genomes and variation of chromosome structures among Roegneria species. We aimed to identify St- and Y-enhanced repeat clusters and to study whether homoeologous chromosomes between St and Y genomes could be accurately identified due to high affinity. We employed comparative genome analyses to identify St- and Y-enhanced repeat clusters and generated a FISH-based karyotype of R. grandis (Keng), one of the taxonomically controversial StY species, for the first time. We explored 4 novel repeat clusters (StY_34, StY_107, StY_90, and StY_93), which could specifically identify individual St and Y nonhomologous chromosomes. The clusters StY_107 and StY_90 could identify St and Y addition/substitution chromosomes against common wheat genetic backgrounds. The chromosomes V_St, VII_St, I_Y, V_Y, and VII_Y displayed similar probe distribution patterns in the proximal region, indicating that the high affinity between St and Y genome might result from chromosome rearrangements or transposable element insertion among V_St/Y, VII_St/Y, and I_Y chromosomes during allopolyploidization. Our results can be used to employ FISH further to uncover the precise karyotype based on colinearity of Triticeae species by using the wheat karyotype as reference, to analyze diverse populations of the same species to understand the intraspecific structural changes, and to generate the karyotype of different StY-containing species to understand the interspecific chromosome variation.


Assuntos
Cromossomos de Plantas/genética , Elymus/genética , Genoma de Planta/genética , Hibridização in Situ Fluorescente/métodos , Evolução Molecular , Marcadores Genéticos/genética , Cariótipo , Região Organizadora do Nucléolo/genética , Poliploidia , Sequências Repetitivas de Ácido Nucleico/genética , Tetraploidia , Triticum/genética
14.
J Neurosurg ; : 1-9, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243149

RESUMO

OBJECTIVE: The aim of this study was to investigate the epidemiological characteristics, associated risk factors, and prognostic value of glioma-related epilepsy in patients with diffuse high-grade gliomas (DHGGs) that were diagnosed after the 2016 updated WHO classification was released. METHODS: Data from 449 patients with DHGGs were retrospectively collected. Definitive diagnosis was reaffirmed according to the 2016 WHO classification. Seizure outcome was assessed using the Engel classification at 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors associated with preoperative and postoperative glioma-related epilepsy. Lastly, the prognostic value of glioma-related epilepsy was evaluated by Kaplan-Meier and Cox analysis. RESULTS: The incidence of glioma-related epilepsy decreased gradually as the malignancy of the tumor increased. Age < 45 years (OR 2.601, p < 0.001), normal neurological function (OR 3.024, p < 0.001), and lower WHO grade (OR 2.028, p = 0.010) were independently associated with preoperative glioma-related epilepsy, while preoperative glioma-related epilepsy (OR 7.554, p < 0.001), temporal lobe involvement (OR 1.954, p = 0.033), non-gross-total resection (OR 2.286, p = 0.012), and lower WHO grade (OR 2.130, p = 0.021) were identified as independent predictors of poor seizure outcome. Furthermore, postoperative glioma-related epilepsy, rather than preoperative glioma-related epilepsy, was demonstrated as an independent prognostic factor for overall survival (OR 0.610, p = 0.010). CONCLUSIONS: The updated WHO classification seems conducive to reveal the distribution of glioma-related epilepsy in DHGG patients. For DHGG patients with high-risk predictors of poor seizure control, timely antiepileptic interventions could be beneficial. Moreover, glioma-related epilepsy (especially postoperative glioma-related epilepsy) is associated with favorable overall survival.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34251297

RESUMO

Compromised endothelial (EC) barrier function is a hallmark of inflammatory diseases. Mammalian target of rapamycin (mTOR) inhibitors, widely applied as clinical therapies, cause pneumonitis through mechanisms not yet fully understood. This study aimed to elucidate the EC mechanisms underlying the pathogenesis of pneumonitis caused by mTOR inhibition (mTORi). Mice with EC-specific deletion of mTOR complex components (Mtor, Rptor or Rictor) were administered LPS to induce pulmonary injury. Cultured EC were treated with pharmacological inhibitors, small interfering RNA or overexpression-plasmids. EC barrier function was evaluated in vivo with Evan's blue assay and in vitro by measurement of transendothelial electrical resistance and albumin flux. mTORi increased basal and TNFα-induced EC permeability, which was caused by myosin light chain (MLC) phosphorylation-dependent cell contraction. Inactivation of mTOR kinase activity by mTORi triggered PKCδ/p38/NF-κB signaling that significantly upregulated TNFα-induced MLC kinase (MLCK) expression, while Raptor promoted the phosphorylation of PKCα/MYPT1 independent of its interaction with mTOR, leading to suppression of MLC phosphatase (MLCP) activity. EC-specific deficiency in mTOR, Raptor or Rictor aggravated lung inflammation in LPS-treated mice. These findings reveal that mTORi induces PKC-dependent endothelial MLC phosphorylation, contraction and hyperpermeability that promote pneumonitis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34309364

RESUMO

The zinc-ion battery (ZIB) is a novel energy storage device, an attractive alternative to the lithium-ion battery. The frequently used aqueous electrolyte suffers from many problems such as zinc dendrites and leakage, which prompts hydrogel electrolytes and solid electrolytes as good replacements. However, hydrogel electrolytes are usually unstable, owing to water volatilization. Herein, a novel solid polymer electrolyte (SPE) utilizing coordination of zinc ions is designed and then introduced into an all-solid ZIB. Benefiting from the unique coordination structure between the polymer and zinc ions, the SPE shows outstanding flexibility, high ion conductivity, and self-healing properties. In addition, the imine bonds in the polymer allow the electrolyte to degrade in acid environments, endowing its recyclability. More importantly, solid-state ZIBs based on the polymer electrolytes exhibit an impressive cycling stability (125% capacity retention after 300 cycles) and a high coulombic efficiency (94% after 300 cycles). The results demonstrate the promising potentials of the developed SPEs that can be used in all-solid ZIBs.

17.
Chem Biol Drug Des ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34288496

RESUMO

Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin, has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TNF-related apoptosis-inducing ligand (TRAIL)-mediated death receptor 5 to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that epidermal growth factor receptor (EGFR), PI3K, and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC.

18.
Clin Immunol ; 229: 108773, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102315

RESUMO

BACKGROUND: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known. METHODS: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/µL, n = 13) and CR (CD4 counts ≥500 cells/µL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively. RESULTS: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1+CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts. CONCLUSIONS: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.


Assuntos
Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Adulto , Contagem de Linfócito CD4 , China , DNA Viral/sangue , DNA Viral/genética , Progressão da Doença , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Fatores de Tempo , Carga Viral/efeitos dos fármacos
19.
Environ Pollut ; 286: 117575, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34130116

RESUMO

High cadmium (Cd) concentration in common wheat (Triticum aestivum L.) grains poses potential health risks. Several management strategies have been used to reduce grain Cd concentration. However, limited information is available on the use of ammonium-nitrogen (NH4+-N) as a strategy to manage Cd concentration in wheat grains. In this study, NH4+-N addition at the seedling stage unchanged the grain Cd concentration in the high-Cd accumulator, Zhoumai 18 (ZM18), but dramatically increased that in the low-Cd accumulator, Yunmai 51 (YM51). Further analysis revealed that the effects of NH4+-N addition on whole-plant Cd absorption, root-to-shoot Cd translocation, and shoot-to-grain Cd remobilization were different between the two wheat cultivars. In ZM18, NH4+-N addition did not change whole-plant Cd absorption, but inhibited root-to-shoot Cd translocation and Cd remobilization from lower internodes, lower leaves, node 1, and internode 1 to grains via the down-regulation of yellow stripe-like transporters (YSL), zinc transporters (ZIP5, ZIP7, and ZIP10), and heavy-metal transporting ATPases (HMA2). This inhibition decreased the grain Cd content by 29.62%, which was consistent with the decrease of the grain dry weight by 23.26%, leading to unchanged grain Cd concentration in ZM18. However, in YM51, NH4+-N addition promoted continuous Cd absorption during grain filling, root-to-shoot Cd translocation and whole-plant Cd absorption. The absorbed Cd was directly transported to internode 1 via the xylem and then re-transported to grains via the phloem by up-regulated YSL, ZIP5, and copper transporters (COPT4). This promotion increased the grain Cd content by 245.35%, which was higher than the increased grain dry weight by 132.89%, leading to increased grain Cd concentration in YM51. Our findings concluded that the addition of NH4+-N fertilizer at the seedling stage is not suitable for reducing grain Cd concentration in common wheat cultivars.


Assuntos
Compostos de Amônio , Proteínas de Transporte de Cátions , Poluentes do Solo , Cádmio/análise , Grão Comestível/química , Retículo Endoplasmático/metabolismo , Nitrogênio , Plântula/metabolismo , Poluentes do Solo/análise , Triticum/metabolismo , Zinco/análise
20.
Mol Ther ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34174439

RESUMO

The programmable nuclease technology CRISPR-Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR-Cas9 therapeutically. Here, we utilized a rhesus macaque model to compare the predictive values of CIRCLE-seq, an in vitro off-target prediction method, with in silico prediction (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing to validate off-target sites predicted by CIRCLE-seq and ISP for a CD33 guide RNA (gRNA) with thousands of off-target sites predicted by ISP and CIRCLE-seq. We found poor correlation between the sites predicted by the two methods. When almost 500 sites predicted by each method were analyzed by error-corrected sequencing of hematopoietic cells following transplantation, 19 off-target sites revealed insertion or deletion mutations. Of these sites, 8 were predicted by both methods, 8 by CIRCLE-seq only, and 3 by ISP only. The levels of cells with these off-target edits exhibited no expansion or abnormal behavior in vivo in animals followed for up to 2 years. In addition, we utilized an unbiased method termed CAST-seq to search for translocations between the on-target site and off-target sites present in animals following transplantation, detecting one specific translocation that persisted in blood cells for at least 1 year following transplantation. In conclusion, neither CIRCLE-seq or ISP predicted all sites, and a combination of careful gRNA design, followed by screening for predicted off-target sites in target cells by multiple methods, may be required for optimizing safety of clinical development.

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