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1.
Environ Pollut ; 282: 117010, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33848913

RESUMO

This study was undertaken to (a) evaluate the destructive effects of chronic exposure to low-dose of chlorpyrifos (CPF) on antioxidant system and immune function in largemouth bass (Micropterus salmoides), and (b) to examine whether dietary supplementation of curcumin can mitigate the adverse effects induced by CPF contamination. The experiment consisted of three groups (with three replicates, 30 fish per replicate) which lasted for 60 days: A control group (without CPF exposure or CU application), CP group (exposed to 0.004 mg/L of CPF), and CU group (exposed to 0.004 mg/L of CPF and fed a diet containing 100 mg curcumin per kg feed). The results showed that CPF contamination leads to reduced weight gain, severe histopathological lesions, decreased activity of antioxidant enzymes and down-regulated expression of antioxidant-related genes. Moreover, CPF upregulated the expression of pro-inflammatory genes such as TNF-α, IL-8, IL-15, downregulated anti-inflammatory genes TGF-ß1, IL-10, and promoted apoptosis through overexpression of Caspase-3, Caspase-8, caspase-9 and Bax. In addition, curcumin supplementation showed significant improvement in oxidative stress, apoptosis and immune dysfunction, but the improved effect gradually weakened during the exposure last. Gas chromatography-mass spectrometry (GC-MS) analysis for accumulation of CPF in muscle supported the changes of general physiological structure, excessive apoptotic responses, abnormal antioxidant and immune system functions and posed potential human health risks to children based on target hazard quotient. These results suggested that chronic exposure to CPF can cause oxidative stress, apoptosis and immune dysfunction, and that curcumin have the potential to reduce pesticides residues in fish. This also highlights the importance of monitoring pesticides residues in aquatic products and aquaculture aquatic environments.

2.
Channels (Austin) ; 15(1): 375-385, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33825659

RESUMO

As the most common histologic subtype of renal cancer, clear cell renal cell carcinoma (ccRCC) poses a serious threat to public health. However, there are no specific molecular-targeted drugs for ccRCC at present. Human ATP-binding cassette (ABC) transporter family plays an important role in homeostasis maintenance. This study aimed to evaluate the potential diagnostic value of ABC genes in ccRCC. A total of 952 samples of ccRCC patients (707) and controls (245) from three different datasets were included for analysis. Receiver operating characteristic analysis and t-test were used to analyze the differential expression of ABC genes in ccRCC patients and control samples at mRNA level during screening and validations. The Cancer Genome Atlas (TCGA-ccRCC) dataset was utilized to investigate the correlation between ABC genes expression and prognostic value in ccRCC. We then investigated the interactions between ABCG1 and proteins in the Comparative Toxicogenomics Database (CTD). Finally, we found that ATP-binding cassette transporter G member 1 (ABCG1) was over-expressed in ccRCC patients compared with healthy samples at mRNA level. Cox regression analysis and Kaplan-Meier analysis showed that ccRCC patients with high ABCG1 expression had better overall survival (OS) than those patients with low expression (hazard ratio (HR) = 0.662, p = 0.007). This study demonstrated that ABCG1 is a potential diagnostic and prognostic biomarker in ccRCC and discussed the molecular mechanisms underlying the relationship between ccRCC and ABCG1, which might provide guidance for better management and treatment of ccRCC in the future.

3.
Cytometry A ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33840152

RESUMO

Cervical cancer is a major gynecological malignant tumor that threatens women's health. Current cytological methods have certain limitations for cervical cancer early screening. Light scattering patterns can reflect small differences in the internal structure of cells. In this study, we develop a light scattering pattern specific convolutional network (LSPS-net) based on deep learning algorithm and integrate it into a 2D light scattering static cytometry for automatic, label-free analysis of single cervical cells. An accuracy rate of 95.46% for the classification of normal cervical cells and cancerous ones (mixed C-33A and CaSki cells) is obtained. When applied for the subtyping of label-free cervical cell lines, we obtain an accuracy rate of 93.31% with our LSPS-net cytometric technique. Furthermore, the three-way classification of the above different types of cells has an overall accuracy rate of 90.90%, and comparisons with other feature descriptors and classification algorithms show the superiority of deep learning for automatic feature extraction. The LSPS-net static cytometry may potentially be used for cervical cancer early screening, which is rapid, automatic and label-free.

4.
Adv Ther ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821431

RESUMO

INTRODUCTION: The IMpower110 trial evaluated the efficacy and safety of atezolizumab in previously untreated patients with metastatic non-small cell lung cancer (NSCLC). Due to the high cost of immunity inhibitors, it is necessary to evaluate their value based on their efficacy and cost. This study evaluated the cost-effectiveness of atezolizumab as the first-line treatment for NSCLC with high programmed cell death ligand 1 (PD-L1) expression from the US payer perspective. METHODS: A Markov model with three health states was developed to estimate the cost and outcome of atezolizumab versus platinum-based chemotherapy in patients with previously untreated metastatic NSCLC with high PD-L1 expression. Model outputs included the life-years (LYs), quality-adjusted LYs (QALYs), total cost, and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed for all parameters. RESULTS: Atezolizumab produced an additional 1.32 QALYs (2.08 LYs) compared with platinum-based chemotherapy. The accompanying incremental cost was US$224,590. The results of one-way sensitivity analysis found that the ICER was most sensitive to the HR of OS. The probabilistic sensitivity analysis showed that the probability of atezolizumab being cost-effective compared with platinum-based chemotherapy was 10.28% and 37.71% at the willing-to-pay (WTP) threshold of $100,000/QALY and $150,000/QALY, respectively. CONCLUSION: Atezolizumab was estimated not to be cost-effective compared with platinum-based chemotherapy in the first-line treatment of patients with NSCLC with high PD-L1 expression.

5.
Proc Natl Acad Sci U S A ; 118(15)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33833061

RESUMO

Density estimation is one of the fundamental problems in both statistics and machine learning. In this study, we propose Roundtrip, a computational framework for general-purpose density estimation based on deep generative neural networks. Roundtrip retains the generative power of deep generative models, such as generative adversarial networks (GANs) while it also provides estimates of density values, thus supporting both data generation and density estimation. Unlike previous neural density estimators that put stringent conditions on the transformation from the latent space to the data space, Roundtrip enables the use of much more general mappings where target density is modeled by learning a manifold induced from a base density (e.g., Gaussian distribution). Roundtrip provides a statistical framework for GAN models where an explicit evaluation of density values is feasible. In numerical experiments, Roundtrip exceeds state-of-the-art performance in a diverse range of density estimation tasks.

6.
BMC Infect Dis ; 21(1): 328, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827456

RESUMO

BACKGROUND: The epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination. METHODS: A retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People's Hospital for cervical screening during 2012-2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed. RESULTS: The overall HPV prevalence was 18.71% (95% confidence interval [CI], 18.55-18.88%) among Southern China females. During 2012-2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07-22.20%) in 2012 to 18.75% (95% CI, 18.35-19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13-35.15%), 20.07% (95% CI, 19.70-20.44%) among women aged 21-30 years, 17.29% (95% CI, 17.01-17.57%) among women aged 31-40 years, 17.23% (95% CI, 16.95-17.51%) among women aged 41-50 years, 21.65% (95% CI, 21.11-22.20%) among women aged 51-60 years, and 25.95% (95% CI, 24.86-27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11-22.20%), - 16 (2.96%; 95% CI, 2.89-3.03%), and - 58 (2.51%; 95% CI, 2.44-2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80-1.92%) and - 6 (0.69%; 95% CI, 0.66-0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study. CONCLUSIONS: This study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012-2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, - 16 and - 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.

7.
Gen Physiol Biophys ; 40(2): 115-126, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33880998

RESUMO

Emerging evidence proposes that circular RNAs (circRNAs) are involved in epileptogenesis. This study aimed to investigate the role and the function mechanism of circ_0003170 in epilepsy models in vitro. Epilepsy models were established in human hippocampal neurons treated by magnesium-free (Mg2+-free) solution. The expression of circ_003170, miR-421 and C-C motif chemokine ligand 2 (CCL2) was detected by qRT-PCR. The putative interaction between miR-421 and circ_003170 or CCL2 was validated by dual-luciferase reporter assay and RIP assay. The protein level of CCL2 was detected by Western blot. Cell viability was detected by CCK-8 assay, and cell cycle and apoptosis were monitored by flow cytometry. The content of superoxide dismutase (SOD) and malondialdehyde (MDA) and the activity of caspase-3 were assessed using commercial kits. The results showed that circ_0003170 and CCL2 expression was enhanced, while miR-421 expression was declined in temporal lobe epilepsy serum specimens and Mg2+-free-induced neurons. circ_0003170 knockdown ameliorated Mg2+-free-induced cell cycle arrest, oxidative stress and apoptosis in neurons by enriching miR-421. Further analysis presented that miR-421 overexpression alleviated Mg2+-freeinduced cell injuries by depleting CCL2. CCL2 overexpression reversed the effects of circ_0003170 knockdown. Overall, circ_0003170 knockdown ameliorated Mg2+-free-induced human hippocampal neuron injuries by mediating the miR-421/CCL2 axis.


Assuntos
Epilepsia , MicroRNAs , RNA Circular/genética , Quimiocina CCL2 , Quimiocinas , Epilepsia/genética , Hipocampo , Humanos , Ligantes , MicroRNAs/genética , Neurônios
8.
Neural Netw ; 140: 344-354, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33930720

RESUMO

Existing trackers usually exploit robust features or online updating mechanisms to deal with target variations which is a key challenge in visual tracking. However, the features being robust to variations remain little spatial information, and existing online updating methods are prone to overfitting. In this paper, we propose a dual-margin model for robust and accurate visual tracking. The dual-margin model comprises an intra-object margin between different target appearances and an inter-object margin between the target and the background. The proposed method is able to not only distinguish the target from the background but also perceive the target changes, which tracks target appearance changing and facilitates accurate target state estimation. In addition, to exploit rich off-line video data and learn general rules of target appearance variations, we train the dual-margin model on a large off-line video dataset. We perform tracking under a Siamese framework using the constructed appearance set as templates. The proposed method achieves accurate and robust tracking performance on five public datasets while running in real-time. The favorable performance against the state-of-the-art methods demonstrates the effectiveness of the proposed algorithm.

9.
Adv Ther ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33770365

RESUMO

INTRODUCTION: The ALCYONE trial found that daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) can significantly improve progression-free survival (PFS) and overall survival (OS) for patients with transplant-ineligible, newly diagnosed multiple myeloma (MM) in China. In the present study, we evaluated the cost-effectiveness of D-VMP versus VMP for patients with newly diagnosed MM in China. METHODS: A Markov model was used to estimate the cost-effectiveness of frontline D-VMP versus VMP for MM. The life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed to assess the robustness of the model and address uncertainties in variable estimates. Subgroup analysis was also performed. RESULTS: D-VMP provided an additional 2.99 LYs and 1.67 QALYs compared with VMP, with incremental $64,920 per LY and $116,015 per QALY gained. The results of the univariable sensitivity analysis showed that the parameter that had the greatest impact on the ICER was the cost of subsequent treatment and daratumumab. When the cost of daratumumab was 100%, 70%, 50%, and 30% of the current price, the probability of D-VMP being cost-effective was 2.49%, 16.11%, 39.09%, and 70.73% at the willingness-to-pay (WTP) threshold of $30,950/QALY, respectively. The results demonstrated that the ICER in all subgroups remained > $30,950/QALY. CONCLUSION: D-VMP versus VMP is likely to exceed the commonly accepted values of cost-effectiveness in patients with transplant-ineligible, newly diagnosed MM in China.

10.
Bioorg Med Chem ; 36: 116094, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667898

RESUMO

EGFR inhibitors represent a significant milestone for treatment of non-small cell lung cancer, however, they suffer from the acquired drug resistance. Utilizing osimertinib as the lead compound, this work has explored the structural modifications on the indole and pyrimidine rings of osimertinib to generate novel osimertinib derivatives. The in vitro enzymatic and cellular studies showed that the derivatives possessed high selectivity towards double mutant EGFR and potent antitumor activity. Particularly, compound 6b-1, the most active compound, exhibited excellent inhibitory activity against double mutant EGFR (IC50 = 0.18 nM) and wild-type EGFR (IC50 = 2.89 nM) as well as H1975 cells (IC50 = 1.44 nM). Western blot analysis showed that 6b-1 completely inhibited double mutant EGFR and Erk phosphorylation. In vivo test using xenograft model indicated that compound 6b-1 had better antitumor efficacy than osimertinib. More importantly, 6b-1 displayed many advantages in the pharmacokinetic study, including better oral bioavailability and metabolism character.

11.
Zhen Ci Yan Jiu ; 46(2): 111-6, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788431

RESUMO

OBJECTIVE: To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR. METHODS: New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation. In the INA group, bilateral "Neiyingxiang" (EX-HN9) within the nasal cavity (the anterior attachment area of the inferior turbinate, about 1 cm away from the nasal limen) were acupunctured by mani-pulating the filiform needles for a while with uniform reinforcing and reducing methods, followed by keeping the needles for 20 min. In the NAA group, shallow acupuncture was applied to the skin of the outer margin of the cheeks, followed by keeping the needle for 20 min. The acupuncture treatment was conducted once every other day for 7 days. The symptoms of sneezing frequency, nasal secretion amount and nasal itching were scored. The expression levels of SP, VIP and NPY in the nasal mucosa tissue were detected by immunohistochemistry, and the serum IgE, IL-4, and IFN-γ contents were detected by ELISA. RESULTS: After modelling, the symptom score, expression of SP and VIP, and serum IgE and IL-4 contents were significantly higher (P<0.01,P<0.05), NPY expression and serum IFN-γ content significantly lower (P<0.05, P<0.01) in the model group than in the normal control group. Following the intervention, the symptom scores, expressions of SP and VIP, and serum IgE and IL-4 contents were remarkably decreased (P<0.05, P<0.01), while the NPY expression and serum IFN-γ content were significantly up-regulated (P<0.05, P<0.01) in the INA group than in the model group. The effects of INA group were significantly superior to those of NAA group in reducing symptom score, SP and VIP expression, and serum IgE and IL-4 contents and up-regulating NPY expression and IFN-γcontent (P<0.05, P<0.01). There were a positive correlation between the expressions of SP and VIP and contents of serum IgE and IL-4 (P<0.05), and a negative correlation between the expressions of SP and VIP and IFN-γ content (P<0.05). CONCLUSION: INA treatment can relieve symptoms of AR in AR rabbits, which may be associated with its effects in regulating the expression of SP, VIP and NPY of the nasal mucosa, and contents of serum IgE, IL-4 and IFN-γ to improve neurogenic inflammation.


Assuntos
Terapia por Acupuntura , Rinite Alérgica , Animais , Imunoglobulina E , Mucosa Nasal , Inflamação Neurogênica , Coelhos , Rinite Alérgica/genética , Rinite Alérgica/terapia
12.
J Travel Med ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763689

RESUMO

Background Malaria is a life-threatening disease worldwide, but lacks studies on its incidence at the global level. We aimed to describe global trends and regional diversities in incidence of malaria infection, to make global tailored implications for malaria prevention. Methods We used the data from the Global Burden of Disease Study 2019. The age-standardized incidence rate (ASR) and absolute number of malaria episodes showed the epidemic status of malaria infection. The estimated annual percentage change (EAPC) of ASR and changes in malaria episodes quantified the malaria incidence trends. The connection between ASRs and traveler number indicated infection risk for travelers. Results Globally, the malaria ASR decreased by an average 0.80% (95%CI 0.58%-1.02%) per year from 1990 to 2019; however, it slightly increased from 3195.32 per 100 000 in 2015 to 3247.02 per 100 000 in 2019. The incidence rate of children under 5 was higher than other age groups. 40 countries had higher ASRs in 2019 than in 2015, with the largest expansion in Cabo Verde (from 2.02 per 100 000 to 597.00 per 100 000). After 2015, the ASRs in high-middle, middle and low-middle SDI (the Socio-demographic Index) regions began to rise, and the uptrends remained in 2019. Central, Western and Eastern Sub-Saharan Africa had the highest ASRs since 1990, and traveler number in Eastern and Western sub-Saharan Africa increased by 31.24% and 7.58%, respectively from 2017 to 2018. Especially, most countries with ASR over 10 000 per 100 000 had increase in traveler number from 2017 to 2018, with the highest change by 89.56% in Mozambique. Conclusions Malaria is still a public health threat for locals and travelers in sub-Sharan Africa and other malaria-endemic areas, especially for children under 5. There were unexpected global uptrends of malaria ASRs from 2015 to 2019. More studies are needed to achieve the goal of malaria elimination.

13.
BMC Surg ; 21(1): 127, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750374

RESUMO

BACKGROUND: Gasless trans-axillary endoscopic thyroidectomy (GTAET) has satisfactory cosmetic effects for the patients who have benign goiter and small thyroid carcinoma, however the complications of this surgical procedure have not been fully documented. Ipsilateral hypoglossal nerve palsy (IHNP) associated with GTAET has never been reported before. CASE PRESENTATION: A 33-year old male patient presented with a 4 × 5 mm solid thyroid nodule in the right lobe. Papillary thyroid carcinoma was confirmed by the fine needle aspiration. He had strong cosmetic demand, therefore GTAET for right lobectomy and central cervical lymphadenectomy was performed in a supine position with cervical extension. Six hours after the operation, he developed tongue deviation to the right side, speech and swallowing difficulties, indicating IHNP. Head and cervical MRI showed no abnormality. The intravenous steroid was used for three days, and oral vitamin B1 and mecobalamin was prescribed for 1 month. Nine days after surgery, he was discharged. Three months after the operation, all the symptoms were completely resolved. CONCLUSIONS: To the best of the authors' knowledge, this is the first case of IHNP after GTAET, which will be valuable to add our knowledge to diagnose and treat rare complications of GTAET.


Assuntos
Endoscopia , Doenças do Nervo Hipoglosso , Neoplasias da Glândula Tireoide , Tireoidectomia , Adulto , Endoscopia/efeitos adversos , Endoscopia/métodos , Humanos , Doenças do Nervo Hipoglosso/diagnóstico , Doenças do Nervo Hipoglosso/etiologia , Masculino , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos
14.
Artigo em Inglês | MEDLINE | ID: mdl-33705666

RESUMO

Rationale Newly diagnosed tuberculosis patients often have inconsistent glycemic measurements during and after treatment. Distinct glycemic trajectories after tuberculosis diagnosis are not well characterized and whether patients with stress hyperglycemia have poor treatment outcomes is not known. Objectives To identify distinct glycemic trajectories from tuberculosis diagnosis to post-treatment and to assess the relationship between glycemic trajectories and tuberculosis treatment outcomes. Methods Newly diagnosed, drug-susceptible tuberculosis patients with at least three fasting plasma glucose (FPG) tests at tuberculosis diagnosis and during the 3rd and 6th month of treatment were identified and included from Jiangsu Province, China. Patients were also given an additional FPG test at two and four months post-treatment. Measurements and Main Results Several distinct glycemic trajectories from tuberculosis diagnosis to post-treatment were found including consistently normal glycemic testing (43%), transient hyperglycemia (24%), erratic glycemic instability (12%), diabetes (16%), and consistently hyperglycemic but without diabetes (6%). Compared to participants with a consistently normal glycemic trajectory, patients were more likely to fail treatment if they had transient hyperglycemia (Adjusted Odds Ratio [AOR], 4.20; 95% CI, 1.57-11.25, P=0.004) or erratic glycemic instability (AOR, 5.98; 95% CI, 2.00-17.87; P=0.001). Patients living with diabetes also had higher risk of treatment failure (AOR, 6.56; 95% Confidence Interval [CI], 2.22-19.35, P=0.001), and this was modified by glycemic control and metformin use. Conclusions Among tuberculosis patients without diabetes, glycemic changes were common and may represent an important marker for patient response to tuberculosis treatment.

15.
Sci Rep ; 11(1): 4936, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654201

RESUMO

Fish culture in paddy fields is a traditional aquaculture mode, which has a long history in East Asia. Large-scale loach (Paramisgurnus dabryanus) fast growth is suitable for paddy fields aquaculture in China. The objective of this study was to identify differential expression genes (DEGs) in the brain, liver and muscle tissues between large (LG, top 5% of maximum total length) and small (SG, top 5% of minimum total length) groups using RNA-seq. In total, 150 fish were collected each week and 450 fish were collected at twelfth week from three paddy fields for all the experimental. Histological observation found that the muscle fibre diameter of LG loaches was greater than that of SG loaches. Transcriptome results revealed that the high expression genes (HEGs) in LG loaches (fold change ≥ 2, p < 0.05) were mainly concentrated in metabolic pathways, such as "Thyroid hormone signalling pathway", "Citrate cycle (TCA cycle)", "Carbon metabolism", "Fatty acid metabolism", and "Cholesterol metabolism", and the HEGs in SG loaches were enriched in the pathways related to environmental information processing such as "Cell adhesion molecules (CAMs)", "ECM- receptor interaction" and "Rap1 signalling pathway"; cellular processes such as "Tight junction", "Focal adhesion", "Phagosome" and "Adherens junction". Furthermore, IGFs gene family may play an important role in loach growth for their different expression pattern between the two groups. These findings can enhance our understanding about the molecular mechanism of different growth and development levels of loaches in paddy fields.

16.
Stem Cells Transl Med ; 10(5): 756-772, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33529481

RESUMO

Acute myocardial infarction (MI) resulting from coronary ischemia is a major cause of disability and death worldwide. Transplantation of human embryonic stem cell (hESC)-derived cardiovascular progenitor cells (hCVPCs) promotes the healing of infarcted hearts by secreted factors. However, the hCVPC-secreted proteins contributing to cardiac repair remain largely unidentified. In this study, we investigated protective effects of neurotrophin (NT)-3 secreted from hCVPCs in hearts against myocardial ischemia/reperfusion (I/R) injury and explored the underlying mechanisms to determine the potential of using hCVPC products as a new therapeutic strategy. The implantation of hCVPCs into infarcted myocardium at the beginning of reperfusion following 1 hour of ischemia improved cardiac function and scar formation of mouse hearts. These beneficial effects were concomitant with reduced cardiomyocyte death and increased angiogenesis. Moreover, hCVPCs secreted a rich abundance of NT-3. The cardioreparative effect of hCVPCs in the I/R hearts was mimicked by human recombinant NT-3 (hNT-3) but canceled by NT-3 neutralizing antibody (NT-3-Ab). Furthermore, endogenous NT-3 was detected in mouse adult cardiomyocytes and its level was enhanced in I/R hearts. Adenovirus-mediated NT-3 knockdown exacerbated myocardial I/R injury. Mechanistically, hNT-3 and endogenous NT-3 inhibited I/R-induced cardiomyocyte apoptosis through activating the extracellular signal-regulated kinase (ERK) and reducing the Bim level, resulting in the cardioreparative effects of infarcted hearts together with their effects in the improvement of angiogenesis. These results demonstrate for the first time that NT-3 is a cardioprotective factor secreted by hCVPCs and exists in adult cardiomyocytes that reduces I/R-induced cardiomyocyte apoptosis via the ERK-Bim signaling pathway and promotes angiogenesis. As a cell product, NT-3 may represent as a noncell approach for the treatment of myocardial I/R injury.

17.
Anal Chem ; 93(8): 3671-3676, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33599476

RESUMO

Surface plasmon coupled emission (SPCE) is a new analytical technique that provides increased and directional radiation based on the near-field interaction between fluorophores and surface plasmons but suffers from the limitation of insufficient sensitivity. The assembly of hollow-porous plasmonic nanoparticles could be the qualified candidate. After the introduction of gold nanocages (AuNCs), fluorescence signal enhancement was realized by factors over 150 and 600 compared with the normal SPCE and free space emission, respectively, with a fluorophore layer thickness of approximately 10 nm; hence, the unique enhancement of SPCE by the AuNCs effectively overcomes the signal quenching induced by resonance energy transfer (in normal SPCE). This enhancement was proven to be triggered by the superior wavelength match, the enhanced electromagnetic field, and new radiation channel and process induced by the AuNC assembly, which provides an opportunity to increase the detection sensitivity and establish an optimal plasmonic enhancement system. The amplified SPCE system was employed for multiwavelength simultaneous enhancement detection through the assembly of mixed hollow nanoparticles (AuNCs and gold nanoshells), which could broaden the application of SPCE in simultaneous sensing and imaging for multianalytes.

18.
PLoS Comput Biol ; 17(2): e1008653, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33577560

RESUMO

Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. The fast-growing number of anti-cancer drugs has caused the experimental investigation of all drug combinations to become costly and time-consuming. Computational techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combination prediction, several challenges remain. First, the performance of existing methods is suboptimal. There is still much space for improvement. Second, biological knowledge has not been fully incorporated into the model. Finally, many models are lack interpretability, limiting their clinical applications. To address these challenges, we have developed a knowledge-enabled and self-attention transformer boosted deep learning model, TranSynergy, which improves the performance and interpretability of synergistic drug combination prediction. TranSynergy is designed so that the cellular effect of drug actions can be explicitly modeled through cell-line gene dependency, gene-gene interaction, and genome-wide drug-target interaction. A novel Shapley Additive Gene Set Enrichment Analysis (SA-GSEA) method has been developed to deconvolute genes that contribute to the synergistic drug combination and improve model interpretability. Extensive benchmark studies demonstrate that TranSynergy outperforms the state-of-the-art method, suggesting the potential of mechanism-driven machine learning. Novel pathways that are associated with the synergistic combinations are revealed and supported by experimental evidences. They may provide new insights into identifying biomarkers for precision medicine and discovering new anti-cancer therapies. Several new synergistic drug combinations have been predicted with high confidence for ovarian cancer which has few treatment options. The code is available at https://github.com/qiaoliuhub/drug_combination.

19.
Int J Mol Sci ; 22(4)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562219

RESUMO

Seed dormancy and germination are key events in plant development and are critical for crop production, and defects in seed germination or the inappropriate release of seed dormancy cause substantial losses in crop yields. Rice is the staple food for more than half of the world's population, and preharvest sprouting (PHS) is one of the most severe problems in rice production, due to a low level of seed dormancy, especially under warm and damp conditions. Therefore, PHS leads to yield loss and a decrease in rice quality and vitality. We reveal that mutation of OsbZIP09 inhibited rice PHS. Analysis of the expression of OsbZIP09 and its encoded protein sequence and structure indicated that OsbZIP09 is a typical bZIP transcription factor that contains conserved bZIP domains, and its expression is induced by ABA. Moreover, RNA sequencing (RNA-seq) and DNA affinity purification sequencing (DAP-seq) analyses were performed and 52 key direct targets of OsbZIP09 were identified, including OsLOX2 and Late Embryogenesis Abundant (LEA) family genes, which are involved in controlling seed germination. Most of these key targets showed consistent changes in expression in response to abscisic acid (ABA) treatment and OsbZIP09 mutation. The data characterize a number of key target genes that are directly regulated by OsbZIP09 and contribute to revealing the molecular mechanism that underlies how OsbZIP09 controls rice seed germination.


Assuntos
Regulação da Expressão Gênica de Plantas , Genoma de Planta , Germinação , Oryza/crescimento & desenvolvimento , Dormência de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/crescimento & desenvolvimento , Oryza/genética , Proteínas de Plantas/genética , Sementes/genética
20.
Kidney Int ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33631226

RESUMO

Blood phosphate levels are linked to atherosclerotic cardiovascular disease in patients with chronic kidney disease (CKD), but the molecular mechanisms remain unclear. Emerging studies indicate an involvement of hyperphosphatemia in CKD accelerated atherogenesis through disturbed cholesterol homeostasis. Here, we investigated a potential atherogenic role of high phosphate concentrations acting through aberrant activation of sterol regulatory element-binding protein (SREBP) and cleavage-activating protein (SCAP)-SREBP2 signaling in patients with CKD, hyperphosphatemic apolipoprotein E (ApoE) knockout mice, and cultured vascular smooth muscle cells. Hyperphosphatemia correlated positively with increased atherosclerotic cardiovascular disease risk in Chinese patients with CKD and severe atheromatous lesions in the aortas of ApoE knockout mice. Mice arteries had elevated SCAP levels with aberrantly activated SCAP-SREBP2 signaling. Excess phosphate in vitro raised the activity of α-mannosidase, resulting in delayed SCAP degradation through promoting complex-type conversion of SCAP N-glycans. The retention of SCAP enhanced transactivation of SREBP2 and expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, boosting intracellular cholesterol synthesis. Elevated α-mannosidase II activity was also observed in the aortas of ApoE knockout mice and the radial arteries of patients with uremia and hyperphosphatemia. High phosphate concentration in vitro elevated α-mannosidase II activity in the Golgi, enhanced complex-type conversion of SCAP N-glycans, thereby upregulating intracellular cholesterol synthesis. Thus, our studies explain how hyperphosphatemia independently accelerates atherosclerosis in CKD.

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