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1.
Brief Bioinform ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34524404

RESUMO

The cooperativity of transcription factors (TFs) is a widespread phenomenon in the gene regulation system. However, the interaction patterns between TF binding motifs remain elusive. The recent high-throughput assays, CAP-SELEX, have identified over 600 composite DNA sites (i.e. heterodimeric motifs) bound by cooperative TF pairs. However, there are over 25 000 inferentially effective heterodimeric TFs in the human cells. It is not practically feasible to validate all heterodimeric motifs due to cost and labor. We introduce DeepMotifSyn, a deep learning-based tool for synthesizing heterodimeric motifs from monomeric motif pairs. Specifically, DeepMotifSyn is composed of heterodimeric motif generator and evaluator. The generator is a U-Net-based neural network that can synthesize heterodimeric motifs from aligned motif pairs. The evaluator is a machine learning-based model that can score the generated heterodimeric motif candidates based on the motif sequence features. Systematic evaluations on CAP-SELEX data illustrate that DeepMotifSyn significantly outperforms the current state-of-the-art predictors. In addition, DeepMotifSyn can synthesize multiple heterodimeric motifs with different orientation and spacing settings. Such a feature can address the shortcomings of previous models. We believe DeepMotifSyn is a more practical and reliable model than current predictors on heterodimeric motif synthesis. Contact:  kc.w@cityu.edu.hk.

2.
Mar Environ Res ; 171: 105469, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500299

RESUMO

Products designed to filter ultraviolet (UV) light are responsible for growing levels of anthropogenic environmental contamination. Octinoxate (ONT) is among the most common UV filtering active ingredients in cosmetics and sunscreens. The present study was designed to evaluate the toxicological effects of ONT on the photosynthetic activity of the Chlorella species of marine microalgae. These analyses identified ONT as a potent photo-toxicant, the effects of which were more pronounced upon light exposure relative to in the dark. Short-term ONT exposure had no effect on photosynthetic electron transport capacity in the dark but did significantly reduce the ribulose-1,5-bisphosphate carboxylase/oxygenase activity in Chlorella cells, suggesting that this compound can directly suppress the photosynthetic Calvin cycle. When cells were subsequently exposed to light, the disruption of this cycle resulted in an excess of excitation energy, in turn driving the excessive generation of reactive oxygen species (ROS). ROS-mediated disruption of cellular metabolism further aggravated this ONT-induced microalgal damage. As such, under natural light conditions, these microalgae cells are exposed to increased oxidative stress that impairs their growth and causes pigment bleaching. Restricting the utilization of ONT-containing sunscreens thus has the potential to better preserve the integrity of aquatic and terrestrial ecosystems.

3.
Biomed Mater ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507313

RESUMO

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks ' culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCl2 and ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over one month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonsrated a better printing accuracy(~200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such as aggrecan (agg), collagen Ⅱ (col II), and SRY-box transcription factor 9 (sox- 9) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair.

4.
ACS Synth Biol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542280

RESUMO

Because of the limited understanding of cellular metabolism and regulatory networks, the rational engineering of complex industrial traits remains a grand challenge for the construction of microbial cell factories. Thus the development of simple, efficient, and programmable genome evolution techniques is still in high demanded for industrial biotechnology. In the present study, we established a random base editing (rBE) system for genome evolution in Saccharomyces cerevisiae. By fusing an unspecific single-stranded DNA (ssDNA)-binding protein to a cytidine deaminase, rBE introduced C to T mutations in a genome-wide manner. Specifically, we chose DNA-replication-related proteins, including replication factor A (RFA1, RFA2, and RFA3), DNA primase (PRI1), DNA helicase A (HCS1), and topoisomerase I (TOP1), to mediate the deamination of genomic ssDNA. As a proof of concept, we roughly estimated the rBE-mediated yeast genome mutation rate using the CAN1 mutation/canavanine resistance reporter system. We then evaluated the performance of these rBEs in improving the resistance against isobutanol and acetate and increasing the production of ß-carotene. Finally, we employed the optimal rBE for the continuous genome evolution of a yeast cell factory resistant to 9% isobutanol. Owing to the conservation of DNA replication mechanisms, rBE is generally applicable and theoretically can be adopted for the continuous genome evolution of all organisms.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34480316

RESUMO

In this study, the outcome serves to establish a measurement model to calculate the value of ecosystem services in Lhasa River Basin, China. Following on the principle of resource scarcity, a study paradigm is established according to the influence of natural and socio-economic location differences on the value of ecosystem services. Results show that the total value of ecosystem services in Lhasa River Basin is 104.503 billion yuan. The unit ecosystem service value of natural grassland in the lower reaches is 5.6 times and 1.07 times larger than that in the upper and middle reaches, respectively. The value of ecosystem services is clearly affected by the scarcity of ecosystem services and dependence of economic and social development on the ecosystem. The value of ecosystem services in the upper, middle, and lower reaches were 4.17%, 21.48%, and 74.35%, respectively. It is found that the value of ecosystem services in this particular region differs significantly in the upper, middle, and lower reaches of the basin. The scarcity of ecological resources has increased the value of ecosystem services, which is reflected in the highest value of ecosystem services in the middle of Lhasa River Valley and both sides of the river where population, economy, and ecological demand are relatively concentrated. According to the estimated results, this study proposes a variety of methods to improve the ecosystem service value and analysis of the ecological compensation mechanism, derived from the contribution made by ecological services.

6.
Sensors (Basel) ; 21(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34502841

RESUMO

The COVID-19 pandemic is a significant public health problem globally, which causes difficulty and trouble for both people's travel and public transport companies' management. Improving the accuracy of bus passenger flow prediction during COVID-19 can help these companies make better decisions on operation scheduling and is of great significance to epidemic prevention and early warnings. This research proposes an improved STL-LSTM model (ISTL-LSTM), which combines seasonal-trend decomposition procedure based on locally weighted regression (STL), multiple features, and three long short-term memory (LSTM) neural networks. Specifically, the proposed ISTL-LSTM method consists of four procedures. Firstly, the original time series is decomposed into trend series, seasonality series, and residual series through implementing STL. Then, each sub-series is concatenated with new features. In addition, each fused sub-series is predicted by different LSTM models separately. Lastly, predicting values generated from LSTM models are combined in a final prediction value. In the case study, the prediction of daily bus passenger flow in Beijing during the pandemic is selected as the research object. The results show that the ISTL-LSTM model could perform well and predict at least 15% more accurately compared with single models and a hybrid model. This research fills the gap of bus passenger flow prediction under the influence of the COVID-19 pandemic and provides helpful references for studies on passenger flow prediction.


Assuntos
COVID-19 , Pandemias , Humanos , Redes Neurais de Computação , Fenômenos Físicos , SARS-CoV-2
7.
Artigo em Inglês | MEDLINE | ID: mdl-34516927

RESUMO

Background: We aimed to report our experience in treating ear amputations with microvascular replantation, with the largest sample to date. Methods: Twenty-two patients with complete ear amputation underwent microvascular ear replantation at three medical centers between May 2003 and May 2020. Arterial anastomoses, venous anastomoses, or vein graft were performed depending on different situations. Re-exploration was performed in four patients due to venous congestion (n = 3) or arterial compromise (n = 1). Results: Eleven patients had vascular complications (venous congestion: 10, arterial compromise: 1) and four of them required re-exploration. Three ears were completely salvaged (75%) and one case failed. Eighteen (81.8%) replanted ears survived completely, with 15 repaired ears demonstrating a good contour and 3 ears showing atrophy. Three replanted ears sustained partial loss, and one sustained total loss. Three extraordinary cases with the longest ischemic time, smallest tissue size, and youngest age reported thus far all survived and had cosmetically satisfactory appearances. Statistical analysis indicated no significant correlation between replanted ear survival and potentially influential factors, including ischemic time, number of arterial and venous anastomoses, presence of vein graft, and re-exploration. Conclusions: Microvascular replantation for ear amputations achieved excellent results. It may be considered the primary choice for surgeons with microsurgical skill.

8.
Entropy (Basel) ; 23(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34356457

RESUMO

Short-packet transmission has attracted considerable attention due to its potential to achieve ultralow latency in automated driving, telesurgery, the Industrial Internet of Things (IIoT), and other applications emerging in the coming era of the Six-Generation (6G) wireless networks. In 6G systems, a paradigm-shifting infrastructure is anticipated to provide seamless coverage by integrating low-Earth orbit (LEO) satellite networks, which enable long-distance wireless relaying. However, how to efficiently transmit short packets over a sizeable spatial scale remains open. In this paper, we are interested in low-latency short-packet transmissions between two distant nodes, in which neither propagation delay, nor propagation loss can be ignored. Decode-and-forward (DF) relays can be deployed to regenerate packets reliably during their delivery over a long distance, thereby reducing the signal-to-noise ratio (SNR) loss. However, they also cause decoding delay in each hop, the sum of which may become large and cannot be ignored given the stringent latency constraints. This paper presents an optimal relay deployment to minimize the error probability while meeting both the latency and transmission power constraints. Based on an asymptotic analysis, a theoretical performance bound for distant short-packet transmission is also characterized by the optimal distance-latency-reliability tradeoff, which is expected to provide insights into designing integrated LEO satellite communications in 6G.

9.
BMC Med Genomics ; 14(1): 199, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362365

RESUMO

BACKGROUND: Practical biosignatures and thorough understanding of regulatory processes of hypertrophic obstructive cardiomyopathy (HOCM) are still lacking. METHODS: Firstly, public data from GSE36961 and GSE89714 datasets of Gene Expression Omnibus (GEO), Gene database of NCBI (National Center of Biotechnology Information) and Online Mendelian Inheritance in Man (OMIM) database were merged into a candidate gene set of HOCM. Secondly, weighted gene co-expression network analysis (WGCNA) for the candidate gene set was carried out to determine premier co-expressed genes. Thirdly, significant regulators were found out by virtue of a multi-factor regulatory network of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), microRNAs (miRNAs) and transcription factors (TFs) with molecule interreactions from starBase v2.0 database and TRRUST v2 database. Ultimately, HOCM unsupervised clustering and "tsne" dimensionality reduction was employed to gain hub genes, whose classification performance was evaluated by a multinomial model of lasso logistic regression analysis binded with receiver operating characteristic (ROC) curve. RESULTS: Two HOCM remarkably-interrelated modules were from WGCNA, followed by the recognition of 32 crucial co-expressed genes. The multi-factor regulatory network disclosed 7 primary regulatory agents, containing lncRNAs (XIST, MALAT1, and H19), TFs (SPI1 and SP1) and miRNAs (hsa-miR-29b-39 and has-miR-29a-3p). Four clusters of HOCM and 4 hub genes (COMP, FMOD, AEBP1 and SULF1) significantly expressing in preceding four subtypes were obtained, while ROC curve demonstrated satisfactory performance of clustering and 4 genes. CONCLUSIONS: Our consequences furnish valuable resource which may bring about prospective mechanistic and therapeutic anatomization in HOCM.

10.
PLoS One ; 16(8): e0254125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411144

RESUMO

Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immune responses in immunocompetent syngeneic tumor transplant models and augment the efficacy of experimental drugs. In this study, we show that the growth rate of Lewis lung carcinoma (LL/2) tumors was reduced after transduction of tdTomato and luciferase (tdTomato/Luc) compared to the parental cell line. tdTomato/Luc expression by LL/2 cells altered the tumor microenvironment by increasing tumor-infiltrating lymphocytes (TILs) while inhibiting tumor-induced myeloid-derived suppressor cells (MDSCs). Interestingly, tdTomato/Luc expression did not alter the response of LL/2 tumors to anti-PD-1 and anti-CTLA-4 antibodies. These results suggest that the use of tdTomato/Luc-transduced cancer cells to conduct studies in immune competent mice may lead to cell-extrinsic tdTomato/Luc-induced alterations in tumor growth and tumor immune microenvironment that need to be taken into consideration when evaluating the efficacy of anti-cancer drugs and vaccines in immunocompetent animal models.

12.
Adv Mater ; : e2102796, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425027

RESUMO

Carbon materials play a critical role in the advancement of electrochemical energy storage and conversion. Currently, it is still a great challenge to fabricate versatile carbon-based composites with controlled morphology, adjustable dimension, and tunable composition by a one-step synthesis process. In this work, a powerful one-step maltose-based puffing carbonization technology is reported to construct multiscale carbon-based composites on large scale. A quantity of composite examples (e.g., carbon/metal oxides, carbon/metal nitrides, carbon/metal carbides, carbon/metal sulfides, carbon/metals, metal/semiconductors, carbon/carbons) are prepared and demonstrated with required properties. These well-designed composites show advantages of large porosity, hierarchical porous structure, high conductivity, tunable components, and proportion. The formation mechanism of versatile carbon composites is attributed to the puffing-carbonization of maltose plus in situ carbothermal reaction between maltose and precursors. As a representative example, Li2 S is in situ implanted into a hierarchical porous cross-linked puffed carbon (CPC) matrix to verify its application in lithium-sulfur batteries. The designed S-doped CPC/Li2 S cathode shows superior electrochemical performance with higher rate capacity (621 mAh g-1 at 2 C), smaller polarization and enhanced long-term cycles as compared to other counterparts. The research provides a general way for the construction of multifunctional component-adjustable carbon composites for advanced energy storage and conversion.

13.
Mol Ecol ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34448283

RESUMO

Quaternary climate oscillations and geographical heterogeneity play important roles in determining species and genetic diversity distribution patterns, but how these factors affect the migration and differentiation of East Asian plants species at the population level remains poorly understood. The Aquilegia ecalcarata complex, a group that originated in the Late Tertiary and is widely distributed throughout East Asia, displays high genetic variation that is suitable for studying elaborate phylogeographic patterns and demographic history related to the impact of Quaternary climate and geography. We used plastid genome data from 322 individuals in 60 populations of the A. ecalcarata complex to thoroughly explore the impact of Quaternary climate oscillations and geography on the phylogeographic patterns and demographic history of the A. ecalcarata complex through a series of phylogenetic, divergence time estimation, and demographic history analyses. The dry, cold climate and frequent climate oscillations that occurred during the early Pleistocene and the Mid-Pleistocene transition led to the differentiation of the A. ecalcarata complex, which was isolated in various areas. Geographically, the A. ecalcarata complex can be divided into Eastern and Western Clades and five subclades, which conform to the divergence of the East Asian flora. Our results clearly show the impact of Quaternary climate and geography on evolutionary history at the population level. These findings promote the understanding of the relationship between plant genetic differentiation and climate and geographical factors of East Asia at the population level.

15.
Medicine (Baltimore) ; 100(33): e26875, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414939

RESUMO

BACKGROUND: Elevated homocysteine (Hcy) levels showed increasing significance as the predisposing factor for the pathogenesis of atherosclerotic sequelae, including cardiovascular mortality, coronary artery disease, and stroke. There is increasing evidence linking plasma Hcy levels and heart failure (HF). The association between the elevated level of plasma Hcy and HF was examined by meta-analysis and systematic review in this study. METHODS: The PubMed and ScienceDirect databases until April 2020 were utilized to collect previous literature on plasma Hcy levels and the potential relation to HF. The pooled effects were evaluated depending on standardized mean differences (SMDs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software. Potential sources of heterogeneity were assessed with subgroup analysis and sensitivity analysis. RESULTS: A total of 12 research projects including 5506 subjects were selected. For pooled effect, the results confirmed that patients with HF had higher Hcy levels than the control subjects (SMD,1.148 and 95%CI, [0.715, 1.581]). Based on the classification of New York Heart Association (NYHA), the Hcy levels for the group of NYHA I or II (SMD, 1.484 and 95% CI, [0.442, 2.527]) and the group of NYHA III or IV (SMD, 3.361 and 95% CI, [1.902, 4.820]) were significantly increased compared to controls, while the increase was more intensive for the group of NYHA III or IV. Subgroup analyses revealed similar results. CONCLUSION: Our meta-analysis identified that plasma Hcy levels were significantly elevated in HF patients compared to control subjects, which is positively related to the advancement of NYHA class.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Homocisteína/sangue , Humanos
16.
Antimicrob Resist Infect Control ; 10(1): 121, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399840

RESUMO

BACKGROUND: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. STUDY DESIGN: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. RESULTS: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045). CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

17.
Head Neck ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459524

RESUMO

PURPOSE: To evaluate the effectiveness of microwave ablation (MWA) for the treatment of thyroid nodules according to nodule composition. MATERIALS AND METHODS: This study evaluated 171 patients with 180 benign thyroid nodules (BTNs) that had been treated with ultrasound-guided MWA. The volume reduction rate (VRR) of thyroid nodules and factors, which had an influence on the VRR, were assessed. Therapeutic success was defined as a >50% volume reduction at the 12-month follow-up. Multivariate regression analysis was used to identify independent predictors of VRR for BTNs after MWA treatment. RESULTS: The mean diameter and volume of the nodules were 4.3 ± 1.3 cm and 18.9 ± 2.1 ml, respectively. The VRRs at the 1-, 3-, 6-, 12-, 24-, and 36-month follow-ups were 47.1%, 68.2%, 79.7%, 87.4%, 90.1%, and 93.2%, respectively. Of the 180 BTNs, there were 87 solid, 74 predominantly solid, and 19 predominantly cystic nodules. Solid nodules showed significantly lower VRRs compared with the predominantly solid and predominantly cystic nodules at the 1-, 3-, and 6-month follow-ups. For the multivariate regression analysis, the cyst component was an active prognostic factor for the VRR at the 1-, 3-, and 6-month follow-ups; the cyst component was not significantly associated with the VRR at the 12-, 24-, and 36-month follow-ups. CONCLUSION: Our study suggested that ultrasound-guided MWA is an effective and safe procedure for the treatment of BTNs. Solid nodules indicate a lower VRR and less efficient than predominant solid nodules and predominant cystic nodules after MWA.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34431114

RESUMO

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

19.
J Leukoc Biol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402104

RESUMO

Stem cell-like memory T cells (Tscm), are a newly defined memory T cell subset with characteristics of long life span, consistent self-renewing, rapid differentiation into effector T cells, and apoptosis resistance. These features indicate that Tscm have great therapeutic or preventive purposes, including being applied in chimeric Ag receptor-engineered T cells, TCR gene-modified T cells, and vaccines. However, the little knowledge about Tscm development restrains their applications. Strength and duration of TCR signaling, cytokines and metabolism in the T cells during activation all influence the Tscm development via regulating transcriptional factors and cell signaling pathways. Here, we summarize the molecular and cellular pathways involving Tscm differentiation, and its clinical application for cancer immunotherapy and prevention.

20.
Free Radic Biol Med ; 174: 236-248, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34400297

RESUMO

Mitochondria-mediated oxidative stress and neuronal apoptosis play an important role in early brain injury following subarachnoid hemorrhage (SAH). Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce oxidative stress and cellular apoptosis by maintaining mitochondrial function under stress. The objective of this study is to investigate the effects of PACAP on mitochondria dysfunction - induced oxidative stress and neuronal apoptosis in both vivo and vitro models of SAH. PACAP Knockout CRISPR and exogenous PACAP38 were used to verify the neuroprotective effects of PACAP in rats after endovascular perforation - induced SAH as well as in primary neuron culture after hemoglobin stimulation. The results showed that endogenous PACAP knockout aggravated mitochondria dysfunction - mediated ATP reduction, reactive oxygen species accumulation and neuronal apoptosis in ipsilateral hemisphere at 24 h after SAH in rats. The exogenous PACAP38 treatment provided both short- and long-term neurological benefits by attenuating mitochondria - mediated oxidative stress and neuronal apoptosis after SAH in rats. Consistently, the exogenous PACAP38 treatment presented similar neuroprotection in the primary neuron culture after hemoglobin stimulation. Pharmacological inhibition of adenylyl cyclase (AC) or extracellular signal-regulated kinase (ERK) partly abolished the anti-oxidative stress and anti-apoptotic effects provided by PACAP38 treatment after the experimental SAH both in vivo and in vitro, suggesting the involvement of the AC-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and ERK pathway. Collectively, PACAP38 may serve as a promising treatment strategy for alleviating early brain injury after SAH.


Assuntos
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Hemorragia Subaracnóidea , Animais , Apoptose , Mitocôndrias , Estresse Oxidativo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ratos , Hemorragia Subaracnóidea/tratamento farmacológico
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