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1.
Infect Genet Evol ; : 105164, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34848355

RESUMO

The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously impacts our economic and public health. The potential of emerging variants to increase transmissibility and evade vaccine-induced immunity lets us put more effort to research on viral mutations and explore the pathogenic haplotypes. In this study, we characterized the haplotype and sub-haplotype diversity of SARS-CoV-2 global variants in January-March and the areas with low and high COVID19 vaccination rates in May 2021 by analyzing viral proteome of complete genome sequences published. Phylogenetic tree analysis of the proteomes of SARS-CoV-2 variants with Neighbor-Joining and Maximum Parsimony methods indicated that haplotype 2 variant with nsp12 P323L and Spike D614G was dominant (98.81%), including new sub-haplotypes 2A_1 to 2A_3, 2B_1 to 2B_3, and 2C_1 to 2C_2 emerged post-one-year COVID-19 outbreak. In addition, the profiling of sub-haplotypes indicated that sub-haplotype 2A_1 with the mutations at N501Y, A570D, D614G, P681H, T716I, S982A, and D118H in Spike was over 58% in May 2021 in the high partly vaccinated rate group (US, Canada, and Germany). Meanwhile, the new haplotype 2C_3 bearing the mutations at EFR156-158del, T19R, A222V, L452R, T478K, and D614G in Spike occupied over 54.8% in May 2021 in the low partly vaccinated rate group (India, Malaysia, Taiwan, and Vietnam). Sub-haplotypes 2A_1 and 2C_3 had a meaningful alternation of ACE2-specific recognition site, neutralization epitopes, and furin cleavage site in SARS-CoV-2 Spike protein. The results discovered the haplotype diversity and new sub-haplotypes of SARS-CoV-2 variants post one-year pandemic in January-March 2021, showing the profiles of sub-haplotypes in the groups with low and high partly vaccinated rates in May 2021. The study reports the emergence of new SARS-CoV-2 sub-haplotypes during ongoing pandemic and vaccination in early 2021, which might help inform the response to vaccination strategies.

2.
ACS Synth Biol ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34860511

RESUMO

Transcription factor-based whole-cell biosensors have recently become promising alternatives to conventional analytical methods due to their advantage of simplicity, cost-effectiveness, and environmental friendliness. In this study, we used genetic engineering to develop a whole-cell biosensor based on the activation of promoters by CupR via interactions with gold ions, leading to the expression of reporter genes that yield output signals. Altering the promoter sequences was shown to significantly improve the performance of the biosensor strain in terms of gold-specificity. The detection sensitivity of our engineered strains was 42-fold higher than that of wild-type strains. The linear range of the purposed sensor was 125-1000 nM with a limit of detection at 46.5 nM. The effectiveness of the sensor strain was verified in wastewater samples.

3.
J Orthop Translat ; 31: 41-51, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34804799

RESUMO

Objectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. Methods: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and ß-tricalcium phosphate (ß-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. Results: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. Conclusion: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. The translational potential of this article: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.

4.
BMC Med Inform Decis Mak ; 21(Suppl 10): 273, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781953

RESUMO

BACKGROUND: To meet the needs of aging and dementia patients in Taiwan, this study designed a nursing system that includes communication, location tracking, and fall detection, and early warning services. The main purpose of this research is to provide timely services to the elderly and patients and hope to reduce the burden when the number of nursing staff decreases. This article is a remote disease care service platform with the Internet of Things (IoT) devices to monitor the location of the elderly and whether they have dropped warning alerts. RESULTS: The device is connected to the patient's waist and chest, monitors the patient's movement and behavior, and transmits messages to the back-end system, and informs caregivers through mobile phone applications when unexpected or shocking events occur. The system can identify whether the patient has fallen, accidentally, or long-term inactivity. The device is equipped with sensors that enable it to monitor the patient's location and behavior data through Bluetooth and GPS technology. Finally, we proposed a basic model and an integrated model that will industrialize the system and is expected to play a role in a larger patient population. CONCLUSIONS: The system developed in this research has passed the Activities of Daily Living (ADL) test and verification, and is expected to provide appropriate safety care services for nursing homes and elderly residences.


Assuntos
Doença de Alzheimer , Internet das Coisas , Atividades Cotidianas , Idoso , Doença de Alzheimer/diagnóstico , Cuidadores , Humanos , Casas de Saúde
5.
J Pediatr Nurs ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844824

RESUMO

PURPOSE: This study aimed to explore the relationship between family resilience, coping styles, and self-care among Chinese adolescents with epilepsy. DESIGN AND METHODS: A total of 1238 adolescents with epilepsy in nine tertiary hospitals in China participated in a cross-sectional survey conducted from May 2018 to March 2020. Structural equation modeling was used to analyze the mediating effect. RESULTS: The total scores for family resilience and coping styles were positively correlated with the total self-care status score of adolescents with epilepsy during their transition (r = 0.209, 0.202, P < 0.01). Family resilience was positively correlated with coping style (r = 0.450, P < 0.01). The modified model's fit index included χ2/df = 1.970, P = 0.001, RMSEA = 0.054, TLI = 0.973, CFI = 0.978, GFI = 0.941, AGFI = 0.917, NFI = 0.956, and IFI = 0.978. The confidence interval (CI) was 0.004-0.140 for the indirect effect and 0.033-0.306 for the direct effect. CONCLUSIONS: The self-care status of adolescents with epilepsy during the transitional period is closely related to coping style and family resilience. Coping style mediates family resilience and self-care status. PRACTICE IMPLICATIONS: Healthcare teams should pay attention to the coping ability of adolescents with epilepsy to help them transition smoothly and to improve family functioning. This study provides a theoretical basis for establishing transitional care programs for adolescents with chronic illnesses. The significant mediating effect of coping style should be emphasized in modalities of healthcare that include patient participation.

6.
mSystems ; : e0029921, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783578

RESUMO

Antimicrobial peptides (AMPs) are innate immune components that have recently stimulated considerable interest among drug developers due to their potential as antibiotic substitutes. AMPs are notable for their fundamental properties of microbial membrane structural interference and the biomedical applications of killing or suppressing microbes. New AMP candidates must be developed to oppose antibiotic resistance. However, the discovery of novel AMPs through wet-lab screening approaches is inefficient and expensive. The prediction model investigated in this study may help accelerate this process. We collected both the up-to-date AMP data set and unbiased negatives based on which the protein-encoding methods and deep learning model for AMPs were investigated. The external testing results indicated that our trained model achieved 90% precision, outperforming current methods. We implemented our model on a user-friendly web server, AI4AMP, to accurately predict the antimicrobial potential of a given protein sequence and perform proteome screening. IMPORTANCE Antimicrobial peptides (AMPs) are innate immune components that have aroused a great deal of interest among drug developers recently, as they may become a substitute for antibiotics. New candidates need to fight antibiotic resistance, while discovering novel AMPs through wet-lab screening approaches is inefficient and expensive. To accelerate the discovery of new AMPs, we both collected the up-to-date antimicrobial peptide data set and integrated the protein-encoding methods with a deep learning model. The trained model outperforms the current methods and is implemented into a user-friendly web server, AI4AMP, to accurately predict the antimicrobial properties of a given protein sequence and perform proteome screening. Author Video: An author video summary of this article is available.

7.
Theranostics ; 11(20): 9884-9903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815793

RESUMO

Inflammasome signaling is a reaction cascade that influences immune response and cell death. Although the inflammasomes participate in tumorigenesis, their role as an oncogenic booster or a tumor suppresser is still controversial. Therefore, it is important to comprehensively investigate the inflammasome signaling status across various cancers to clarify its clinical and therapeutic significance. Methods: A total of 9881 patients across 33 tumor types from The Cancer Genome Atlas database were included in this study. Five gene sets were identified to step-wisely profile inflammasome signaling. Unsupervised clustering was used for sample classification based on gene set enrichment. Machine learning and in vitro and in vivo experiments were used to confirm the implications of inflammasome classification. Results: A hundred and forty-one inflammasome-signaling-related genes were identified to construct five gene sets representing the sensing, activation, and termination steps of the inflammasome signaling. Six inflammasome clusters were robustly established with distinct molecular, biological, clinical, and therapeutic features. Importantly, clusters with inflammasome signaling activation were found to be immunosuppressive and resistant to ICB treatment. Inflammasome inhibition reverted the therapeutic failure of ICB in inflammasome-activated tumors. Moreover, based on the proposed classification and therapeutic implications, an open website was established to provide tumor patients with comprehensive information on inflammasome signaling. Conclusions: Our study conducted a systematical investigation on inflammasome signaling in various tumor types. These findings highlight the importance of inflammasome evaluation in tumor classification and provide a foundation for improving relevant therapeutic regimens.

10.
Bioorg Med Chem Lett ; 54: 128437, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34737087

RESUMO

Dengue virus (DENV) causes about 50-100 million cases per year worldwide. However, there is still a big challenge in developing antiviral drugs against DENV infection. Some derivatives of alkaloid (-)-cytisine, like other alkaloid analogs, have been proposed for their antiviral potential. This study investigated antiviral activity and mechanisms of the cytisine derivatives, and discovered the structure-activity relationship against DENV. The antiviral assays were performed using one strain of DENV1 and DENV2, and two cell lines Vero E6 and A549. The structure-activity relationship of the effective compounds was also evaluated using combination of time-of-addition/removal assay and molecular docking. Compounds 3, 4, 12 (N-allylcytisine-3-thiocarbamide), 16, and 20 exhibited the high antiviral activity with IC50 values of lower than 3 µM against DENV1 and DENV2. Of them, the derivative 12 showed the highest antiviral activities against DENV1 (IC50 = 0.14 µM) and DENV-2 (IC50 = <0.1 µM), exhibiting the potent inhibition on virus attachment and entry stages. Meanwhile, the compounds 4 and 20 had a strong inhibition at the post-entry stage (IC50 = <0.1 µM). A correlation between the experimental pIC50 values and predicted pKi calculated by docking of compounds into DENV E protein was significant, correlating with the impact of compound 12 on the attachment stage, but compounds 4, and 20 on post-entry stage. The results provided the insight into the directions of synthetic modifications of starting (-)-cytisine as the inhibitors of DENV E protein at attachment and entry stages of DENV life cycle.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34774478

RESUMO

OBJECTIVES: The aim of this study was to evaluate the clinical impact of computed tomography (CT)-derived pulmonary artery dilatation (PAD) in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Several studies have reported an association between pulmonary hypertension and cardiovascular events, but the prognostic value of PAD in patients undergoing TAVR remains unclear. METHODS: The preprocedural computed tomographic studies of patients who underwent TAVR at Cedars-Sinai Medical Center between November 2013 and December 2017 were analyzed. Patients were divided into 2 groups according to the presence of PAD assessed on CT (pulmonary artery [PA] diameter ≥29 mm). The primary endpoint was all-cause mortality at 2 years. RESULTS: A total of 895 patients were included (mean age 81.3 ± 8.5 years), with a mean Society of Thoracic Surgeons score of 4.8%. The median PA diameter was 28.0 mm, and PAD was observed in 369 patients (41.2%). Compared with the no-PAD group, the PAD group had higher Society of Thoracic Surgeons scores and higher rates of atrial fibrillation, chronic kidney disease, and chronic obstructive pulmonary disease. The PAD group had higher 2-year all-cause mortality than the no-PAD group (28.9% vs 12.8%; P < 0.001), and PAD was independently associated with mortality (adjusted hazard ratio: 2.21; 95% confidence interval: 1.44-3.39; P < 0.001). Furthermore, PAD had strong prognostic power in the subgroup analysis, stratified according to PA pressure (>36 mm Hg). CONCLUSIONS: CT-derived PAD is a significant prognostic factor in patients undergoing TAVR.

12.
Sci Rep ; 11(1): 22042, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764391

RESUMO

The mutation of SARS-CoV-2 influences viral function as residue replacements affect both physiochemical properties and folding conformations. Although a large amount of data on SARS-CoV-2 is available, the investigation of how viral functions change in response to mutations is hampered by a lack of effective structural analysis. Here, we exploit the advances of protein structure fingerprint technology to study the folding conformational changes induced by mutations. With integration of both protein sequences and folding conformations, the structures are aligned for SARS-CoV to SARS-CoV-2, including Alpha variant (lineage B.1.1.7) and Delta variant (lineage B.1.617.2). The results showed that the virus evolution with change in mutational positions and physicochemical properties increased the affinity between spike protein and ACE2, which plays a critical role in coronavirus entry into human cells. Additionally, these structural variations impact vaccine effectiveness and drug function over the course of SARS-CoV-2 evolution. The analysis of structural variations revealed how the coronavirus has gradually evolved in both structure and function and how the SARS-CoV-2 variants have contributed to more severe acute disease worldwide.


Assuntos
COVID-19/virologia , Evolução Molecular , Mutação , SARS-CoV-2/genética , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Humanos , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Mapas de Interação de Proteínas , Multimerização Proteica , Vírus da SARS/química , Vírus da SARS/genética , Vírus da SARS/metabolismo , SARS-CoV-2/química , SARS-CoV-2/metabolismo , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Zhongguo Gu Shang ; 34(10): 911-4, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726017

RESUMO

OBJECTIVE: To investigate the effect of femoral offset (FO) on the postoperative functional results of proximal femoral nail antirotation (PFNA) in femoral trochanteric fractures. METHODS: From May 2017 to June 2019, 112 patients receiving PFNA were analyzed, X-ray and CT examination of both hips were performed before operation, and X-ray examination of both hips of pelvis was performed on the first day after operation. Among them, 71 patients showed bilateral FO difference≤ 5 mm on positive X-ray film (group A), and 41 patients showed bilateral FO difference>5 mm (group B). There was no significant difference between two groups in gender, age, operative side, course of disease, Harris score of preoperative hip joint, preoperativeFO(P>0.05). The Harris score of hip joint at 6 and 12 months was compared between two groups. The correlation between FO difference and Harris score was analyzed. RESULTS: Patients in both groups were followed up for 12 months after surgery, and all patients reached the healing criteria. The difference of Harris score of the hip joint at 6 and 12 months after surgery was statistically significant (P<0.05), and the difference of bilateral FO was negatively correlated with the Harris score of the hip joint at 6 and 12 months after surgery (R=-0.213, P<0.05), (R=-0.335, P<0.05). CONCLUSION: In the treatment of trochanteric fractures with PFNA, the greater the difference of FO between the two sides, the worse the postoperative function of the patients. The appropriate FO(the difference of FO between the two sides ≤5 mm) can improve the postoperative function of the patients.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Pinos Ortopédicos , Fraturas do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
14.
Front Oncol ; 11: 675972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722237

RESUMO

Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.

15.
Front Pharmacol ; 12: 692431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744705

RESUMO

Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification.

16.
Biomed Res Int ; 2021: 6464686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746304

RESUMO

Objective: To explore the mechanisms of follicular fluids (FFs) on granulose cell (GC) apoptosis in endometriosis-associated infertility. Materials and Methods: 60 infertile women were enrolled. The FFs from 30 endometriosis-associated infertility (EI) patients were collected and processed by ELISA hormone assay and proteomic profiling. The ovary GCs collected from 30 tubal-associated infertility (TI) patients were cultured in follicular fluids of endometriosis-associated infertility patients (EI-FFs), and the apoptosis mechanisms were explored by flow cytometry assay, real-time PCR, Western blotting, and protein-protein interaction (PPI) network analysis. Results: Our results showed that the expression of 22 specific proteins was significantly different in the FFs from EI and TI patients, and the level of testosterone and anti-Müllerian hormone was not obviously different between the two groups. EI-FFs could accelerate the apoptosis process of granulose cells of tubal-associated infertility patients (TI-GCs) by regulating the expression of 5 apoptosis-related proteins including BCL2, BAX, CASP3, CASP9, and TP53. The correlation of these 22 specific proteins and 5 apoptosis-related proteins was analyzed by PPI, and 5 protein biomarkers (INS, CXCL10, ICAM1, WIF1, and TNFRSF13C) and 5 signaling pathways (cytokine-cytokine receptor interaction, apoptosis, regulation of actin cytoskeleton, MAPK, and p53 signaling pathway) were predicted. Conclusion: This research clarified the effect and explored the mechanisms of EI-FFs on the apoptosis of TI-GCs and indicated the protein biomarkers and signaling pathways for further study.

17.
IEEE Trans Cybern ; PP2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793316

RESUMO

In recent years, ensemble methods have shown sterling performance and gained popularity in visual tasks. However, the performance of an ensemble is limited by the paucity of diversity among the models. Thus, to enrich the diversity of the ensemble, we present the distillation approach--learning from experts (LFEs). Such method involves a novel knowledge distillation (KD) method that we present, specific expert learning (SEL), which can reduce class selectivity and improve the performance on specific weaker classes and overall accuracy. Through SEL, models can acquire different knowledge from distinct networks with various areas of expertise, and a highly diverse ensemble can be obtained afterward. Our experimental results demonstrate that, on CIFAR-10, the accuracy of the ResNet-32 increases 0.91% with SEL, and that the ensemble trained by SEL increases accuracy by 1.13%. Compared to state-of-the-art approaches, for example, DML only improves accuracy by 0.3% and 1.02% on single ResNet-32 and the ensemble, respectively. Furthermore, our proposed architecture also can be applied to ensemble distillation (ED), which applies KD on the ensemble model. In conclusion, our experimental results show that our proposed SEL not only improves the accuracy of a single classifier but also boosts the diversity of the ensemble model.

18.
Int J Nanomedicine ; 16: 6825-6841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675510

RESUMO

Purpose: Therapeutic efficacy of pancreatic adenocarcinomas (PACs) with combined therapy of carfilzomib (CFZ) and paclitaxel (PTX) co-loaded in human serum albumin (HSA) nanoparticles (NPs) was examined. Methods: CFZ and PTX were encapsulated individually or combined into HSA NPs by a simple reverse self-assembly method developed to achieve an optimal combination ratio for synergistic therapy. CFZ or/and PTX loaded HSA nanoparticles were physically characterized and the evaluation of combination index, drug release, pharmacokinetic, anti-tumor, and biodistribution studies were conducted. Results: All resultant drug-loaded HSA NPs were spherical with a particle size of <150 nm and a zeta potential of -21.1~-23.0 mV. Drug loading rates and entrapment efficiencies were 9.1%~10.1% and 90.7%~97.1%, respectively. CFZ and PTX demonstrated synergistic effects in an MIA PaCa-2 cytotoxicity at a 1:2 ratio (CI50 were 0.01~0.25). In vitro dissolution revealed that the CFZ/PTX ratio released from the co-loaded HSA NPs (CFZ/PTX/HSA NPs) was about 1.77~2.08, which conformed to the designated loaded ratio. In vivo evaluation showed that the combined therapy of CFZ and PTX at a 1:2 ratio co-loaded in HSA NPs (CFZ/PTX/HSA NPs) demonstrated optimal synergistic improvement of the growth inhibition of MIA PaCa-2 cells with less systematic toxicity, even though the pharmacokinetic profiles observed did not show obvious beneficial and their biodistributions in tumors were found to be smaller. Conclusion: The one-pot reverse assembly method developed was environmentally friendly and capable of co-loading an optimal combination ratio of two chemodrugs into HSA NPs for synergistic therapy.


Assuntos
Adenocarcinoma , Nanopartículas , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Oligopeptídeos , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico , Distribuição Tecidual
19.
Mar Biotechnol (NY) ; 23(6): 943-954, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34714446

RESUMO

The pan-genome was defined as the complete gene set across strains, and it is built upon genes displaying presence-absence variations (PAVs); the pan-transcriptome is defined by recalling the pan-genome. Indeed, a PAV is reflected from the expression presence-absence variation (ePAV). In this study, treated with androgen, eels, which are a primitive fish from the basal lineage of Teleost, with different ovarian developments were chosen and submitted to RAN-sequencing. Transcriptomes were the assembly against eel genome scaffolds; a pair was the unit (the same eel before and after treatment) to analyze DEGs (differentially expressed genes); the core, unique, or accessory genes were identified, and the list of DEGs was analyzed to investigate ePAV. The results suggest that there was ePAV in Japanese eel, and the ePAV of eel was analyzed by pathway enrichment. These results signify the importance of genetic differential expression on the variations of phenotypes by androgen, and a transcriptomic approach appears to enable extracting multiple layers of genomic data.

20.
Neurochem Res ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625874

RESUMO

To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia-reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p < 0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p < 0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p < 0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.

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