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1.
J Mol Med (Berl) ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628513

RESUMO

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.

2.
BMJ Glob Health ; 6(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34593512

RESUMO

BACKGROUND: In 2019, there are more than 290 million people who have ever migrated from rural to urban areas in China. These rural-to-urban internal migrants account for more than one-fifth of China's population and is the largest internal migrant group globally. We present the first systematic review that examines whether internal migrants are more likely to exhibit non-communicable diseases (NCDs) risk factors and have worse NCD management outcomes than non-migrant counterparts in China. METHODS: A systematic review was conducted via medical, public health, and economic databases including Scopus, MEDLINE, JSTOR, WHO Library Database and World Bank e-Library from 2000 to 2020. Study quality was assessed using the National Institute of Health Quality Assessment tool. We conducted a narrative review and synthesised differences for all studies included, stratified by different types of outcomes. We also conducted random-effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO: CRD42019139407. RESULTS: For most NCD risk factors and care cascade management, comparisons between internal migrants and other populations were either statistically insignificant or inconclusive. While most studies found migrants have a higher prevalence of tobacco use than urban residents, these differences were not statistically significant in the meta-analysis. Although three out four studies suggested that migrants may have worse access to NCD treatment and both studies suggested migrants have lower blood pressure control rates than non-migrants, these findings were not statistically significant. CONCLUSION: Findings from this systematic review demonstrate that there is currently insufficient evidence on migrant and non-migrant differences in NCD risk factors and management in China. Further research is expected to investigate access to healthcare among internal and its effect on both their NCD outcomes and long-term healthcare costs in China.


Assuntos
Doenças não Transmissíveis , Migrantes , China/epidemiologia , Humanos , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/terapia , Fatores de Risco , População Rural
3.
PLoS Pathog ; 17(10): e1009412, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34597346

RESUMO

Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.

4.
Small ; : e2104513, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605154

RESUMO

Hydrogen economy is imagined where excess electric energy from renewable sources stored directly by electrochemical water splitting into hydrogen is later used as clean hydrogen fuel. Electrocatalysts with the superhigh current density (1000 mA cm-2 -level) and long-term durability (over 1000 h), especially at low overpotentials (<300 mV), seem extremely critical for green hydrogen from experiment to industrialization. Along the way, numerous innovative ideas are proposed to design high efficiency electrocatalysts in line with industrial requirements, which also stimulates the understanding of the mass/charge transfer and mechanical stability during the electrochemical process. It is of great necessity to summarize and sort out the accumulating knowledge in time for the development of laboratory to commercial use in this promising field. This review begins with examining the theoretical principles of achieving high-efficiency electrocatalysts with high current densities and excellent durability. Special attention is paid to acquaint efficient strategies to design perfect electrocatalysts including atomic structure regulation for electrical conductivity and reaction energy barrier, array configuration constructing for mass transfer process, and multiscale coupling for high mechanical strength. Finally, the importance and the personal perspective on future opportunities and challenges, is highlighted.

5.
Bioengineered ; 12(1): 7747-7754, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34617873

RESUMO

We aimed to explore the role of miR-21-5p in the inhibitory effects of astragaloside IV (As-IV) on hypoxia/reoxygenation injury-induced apoptosis of type II alveolar epithelial cells. Rat type II alveolar epithelial cells RLE-6TN were cultured in vitro and randomly divided into control (C), hypoxia/reoxygenation injury (H/R), As-IV and miR-21-5p-siRNA + As-IV groups (n = 6). H/R model was established by 24 h of hypoxia and 4 h of reoxygenation. As-IV group was given 1 nmol/L As-IV and incubated for 1 h before modeling. MiR-21-5p-siRNA + As-IV group was transfected with 50 nmol/L miR-21-5p-siRNA. After 48 h, they were incubated with 1 nmol/L As-IV for 1 h before modeling. Cell viability was detected by cell counting kit-8 assay, and apoptosis rate was detected by flow cytometry. The expression levels of TLR4 and NF-κB were measured by immunofluorescence assay. The targeting relationship between miR-21-5p and TLR4 was determined by luciferase assay. Compared with H/R group, the cell viability, miR-21-5p, bax and cleaved caspase-3 expressions of As-IV group increased, apoptosis rate and Bcl-2 expression decreased, and TLR4 and NF-κB expressions were down-regulated (P < 0.05). Compared with As-IV group, the cell viability, miR-21-5p, bax and cleaved caspase-3 expressions of miR-21-5p-siRNA + As-IV group decreased, apoptosis rate and Bcl-2 expression increased, and the expressions of TLR4 and NF-κB were up-regulated (P < 0.05). As-IV up-regulates miR-21-5p expression, inhibits the TLR4/NF-κB signaling pathway and suppresses the apoptosis of type II alveolar epithelial cells during hypoxia/reoxygenation injury.

6.
Biosens Bioelectron ; 195: 113656, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34600203

RESUMO

Serological tests play an important role in the fight against Coronavirus Disease 2019 (COVID-19), including monitoring the dynamic immune response after vaccination, identifying past infection and determining community infection rate. Conventional methods for serological testing, such as enzyme-linked immunosorbent assays and chemiluminescence immunoassays, provide reliable and sensitive antibody detection but require sophisticated laboratory infrastructure and/or lengthy assay time. Conversely, lateral flow immunoassays are suitable for rapid point-of-care tests but have limited sensitivity. Here, we describe the development of a rapid and sensitive magnetofluidic immuno-PCR platform that can address the current gap in point-of-care serological testing for COVID-19. Our magnetofluidic immuno-PCR platform automates a magnetic bead-based, single-binding, and one-wash immuno-PCR assay in a palm-sized magnetofluidic device and delivers results in ∼30 min. In the device, a programmable magnetic arm attracts and transports magnetically-captured antibodies through assay reagents pre-loaded in a companion plastic cartridge, and a miniaturized thermocycler and a fluorescence detector perform immuno-PCR to detect the antibodies. We evaluated our magnetofluidic immuno-PCR with 108 clinical serum/plasma samples and achieved 93.8% (45/48) sensitivity and 98.3% (59/60) specificity, demonstrating its potential as a rapid and sensitive point-of-care serological test for COVID-19.

7.
Br J Nutr ; : 1-20, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632975

RESUMO

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12,237 non-T2DM participants aged over 18 from the Rural Chinese Cohort Study of 2007-2008 were included at baseline and followed up during 2013-2014. The cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6.01 (5.09-6.06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR (95% CI) for the highest versus lowest METS-VF quartile was 5.97 (4.28-8.32), with a per 1-standard deviation increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose-response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0.0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age, or body mass index.

8.
J Phys Chem Lett ; : 9919-9925, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613722

RESUMO

We study the vacuum Rabi splitting of a qubit ultrastrongly coupled to a high-Q cavity mode and a radiation reservoir. Three methods are employed: a numerically exact variational approach with a multiple Davydov ansatz, the rotating-wave approximation (RWA), and the transformed RWA. Agreement between the variational results and the transformed RWA results is found in the regime of validity of the latter, where the RWA breaks down completely. We illustrate that the Lamb shift plays an essential role in modifying the vacuum Rabi splitting in the ultrastrong coupling regime, leading to off-resonant qubit-cavity coupling even though the cavity frequency equals the bare transition frequency of the qubit. Specifically, the emission spectrum exhibits one broad low-frequency peak and one narrow high-frequency peak in the presence of relatively weak cavity-qubit coupling. As the cavity-qubit coupling increases, the low-frequency peak narrows while the high-frequency peak broadens until they have similar widths.

9.
BMC Cancer ; 21(1): 988, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479538

RESUMO

BACKGROUND: In clinical studies, it has been observed that esophageal cancer (EC) patient prognosis can be very different even for those patients with tumors of the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients. METHODS: A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis. RESULTS: Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR = 1.30; 95% CI: 1.21-1.40, p < .001) and disease-free survival (DFS) (HR = 1.38; 95% CI: 1.18-1.61, p < .001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS). CONCLUSION: The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.

10.
Zhongguo Zhen Jiu ; 41(9): 1049-54, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491657

RESUMO

OBJECTIVE: To analyze the literature knowledge structure and acupoint matching rules of acupuncture for depression. METHODS: The articles regarding acupuncture for depression published from January 1 of 1984 to October 19 of 2020 were searched in CNKI database. CiteSpace5.7.R2 software was used to import the literature data, and the keyword cluster analysis, emergence analysis and time-zone analysis of articles and acupoints were conducted, and the map of scientific knowledge was draw. RESULTS: A total of 3524 articles were included to the knowledge structure analysis, while 601 articles into the acupoint matching rules analysis. There were 13 keyword clusters of acupuncture for depression, with "post-stroke depression" and "electroacupuncture treatment" as high-frequency keywords, and "electroacupuncture treatment" and "Hamilton depression scale" had high centrality, and "electroacupuncture treatment" had the highest emergence intensity. The keywords such as "electroacupuncture treatment" and "Hamilton depression scale", etc. appeared the earliest, followed by "post-stroke depression", "fluoxetine" and "auricular point therapy", etc. According to traditional Chinese medicine theory, acupoint keywords were divided into four clusters: ①core acupoint, ②replenishing-spleen and dispelling phlegm, dispersing-liver and relieving depression, reinforcing qi and nourishing blood, ③back-shu points, five-zhi points, ④inducing-resuscitation and opening-closes. CONCLUSION: The main knowledge structure of acupuncture for depression includes five parts: treatment method, depression type, TCM-related diseases, literature type and curative effect index. Clinical acupoint matching should adhere to the principle of "focusing the disease before syndrome" and "combination of disease and syndrome", and treatment should be modified for the syndromes of phlegm stagnation blocking, liver-stagnation and qi-stagnation, and deficiency of both qi and blood.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Pontos de Acupuntura , Depressão/terapia , Medicina Tradicional Chinesa
11.
Artigo em Inglês | MEDLINE | ID: mdl-34540319

RESUMO

The occurrence of coronavirus disease 2019 (COVID-19) was followed by a small burst of cases around the world; afterward, due to a series of emergency non-pharmaceutical interventions (NPIs), the increasing number of confirmed cases slowed down in many countries. However, the subsequent gradual easing of governance led to a sudden increase in cases in late July 2020, arousing deep concern across the globe. This study evaluates the situation of the COVID-19 pandemic in countries and territories worldwide from January 2020 to February 2021. According to the time-varying reproduction number (R(t)) of each country or territory, the results show that almost half of the countries and territories in the world have never controlled the epidemic. Among the countries and territories that had once contained the occurrence, nearly half failed to maintain their prevention and control, causing the COVID-19 pandemic to rebound across the world-resulting in even higher waves in half of the rebounding countries or territories. This work also proposes and uses a time-varying country-level transmission risk score (CTRS), which takes into account both R(t) and daily new cases, to demonstrate country-level or territory-level transmission potential and trends. Time-varying hierarchical clustering of time-varying CTRS values was used to successfully reveal the countries and territories that contributed to the recent aggravation of the global pandemic in the last quarter of 2020 and the beginning of 2021, and to identify countries and territories with an increasing risk of COVID-19 transmission in the near future. Furthermore, a regression analysis indicated that the introduction and relaxation of NPIs, including workplace closure policies and stay-at-home requirements, appear to be associated with recent global transmission changes. In conclusion, a systematic evaluation of the global COVID-19 pandemic over the past year indicates that the world is now in an unexpected situation, with limited lessons learned. Summarizing the lessons learned could help in designing effective public responses for constraining future waves of COVID-19 worldwide.

12.
Org Biomol Chem ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34545907

RESUMO

Metal-free catalyzed intermolecular tandem Michael addition/cyclization has been developed for the synthesis of benzo[4,5]imidazo[1,2-a]pyridines from α-bromocinnamaldehyde and 2-substituted benzimidazoles. The reaction promoted by a simple inorganic base displays moderate to good yields and good functional group tolerance. The optical properties of some typical products have been investigated. We found that, due to the presence of the benzene ring at the C1-position of benzo[4,5]imidazo[1,2-a]pyridines which restricts intramolecular motion, as a new type of aggregation-induced emission (AIE) luminogen (AIEgen), they show very good solid-state fluorescence with quantum yields up to 88.80%. Importantly, the AIE performance of compound 3b can be useful to detect the nitroaromatic explosive picric acid (PA) with a detection limit and quenching constant of 42.5 nM and 7.27 × 104 M-M, respectively.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34524004

RESUMO

Background: We conducted a trial to evaluate the efficacy and safety of apatinib, a tyrosine inhibitor against vascular endothelial growth factor receptor 2, combined with neoadjuvant chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: One hundred twenty six patients were randomized into two cycles of paclitaxel and cisplatin (TP) (n = 61) or combined with apatinib (Apa+TP) (n = 65), followed by surgery. The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR), safety, R0 resection rate, and operative complication rates. Results: Compared with TP chemotherapy alone, adding apatinib to neoadjuvant treatment significantly increased ORR (Apa+TP: 80.0% vs. TP: 54.1%, respectively; p = 0.004). Apa+TP achieved higher pCR rate compared with TP alone (15.4% vs. 4.92%, respectively; p = 0.101). Similar incidences of toxic effects were found between those two groups. No grade 3 or 4 adverse events (AEs) were observed. Meanwhile, apatinib-related AEs, including hypertension, proteinuria, and hand-and-foot syndrome, were mild. The R0 resection rate was 100% in both groups. No significant differences in operation time, intraoperative bleeding, and postoperative complications were observed, and no serious complications occurred. Conclusions: Adding apatinib to TP neoadjuvant chemotherapy significantly increased ORR, suggesting an advantage of anti-angiogenesis in ESCC. Clinical Trials.gov ID: ChiCTR-TRC-1800017662.

14.
BMC Geriatr ; 21(1): 484, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488653

RESUMO

BACKGROUND: Barthel Index (BI) is one of the most widely utilized tools for assessing functional independence in activities of daily living. Most existing BI studies used populations with specific diseases (e.g., Alzheimer's and stroke) to test prognostic factors of BI scores; however, the generalization of these findings was limited when the target populations varied. OBJECTIVES: The aim of the present study was to utilize electronic health records (EHRs) and data mining techniques to develop a generic procedure for identifying prognostic factors that influence BI score changes among community-dwelling elderly. METHODS: Longitudinal data were collected from 113 older adults (81 females; mean age = 84 years, SD = 6.9 years) in Hong Kong elderly care centers. Visualization technologies were used to align annual BI scores with individual EHRs chronologically. Linear mixed-effects (LME) regression was conducted to model longitudinal BI scores based on socio-demographics, disease conditions, and features extracted from EHRs. RESULTS: The visualization presented a decline in BI scores changed by time and health history events. The LME model yielded a conditional R2 of 84%, a marginal R2 of 75%, and a Cohen's f2 of 0.68 in the design of random intercepts for individual heterogeneity. Changes in BI scores were significantly influenced by a set of socio-demographics (i.e., sex, education, living arrangement, and hobbies), disease conditions (i.e., dementia and diabetes mellitus), and EHRs features (i.e., event counts in allergies, diagnoses, accidents, wounds, hospital admissions, injections, etc.). CONCLUSIONS: The proposed visualization approach and the LME model estimation can help to trace older adults' BI score changes and identify the influencing factors. The constructed long-term surveillance system provides reference data in clinical practice and help healthcare providers manage the time, cost, data and human resources in community-dwelling settings.


Assuntos
Vida Independente , Acidente Vascular Cerebral , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Hong Kong/epidemiologia , Hospitalização , Humanos
15.
Nanotechnology ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517362

RESUMO

Anode materials based on lithium titanate (LTO)/graphene composites are considered as ideal candidates for high-rate lithium-ion batteries (LIBs). Considering the blocking effects of graphene nanosheets in electrodes during ion-transfer processes, construction of LTO/graphene composite structures with enhanced electrical and ionic conductivity via facile and scalable techniques is still challenging for high-rate lithium-ion batteries. In this work, structures of anode materials based on LTO nanoplates embedded with graphene quantum dots (GQDs) are demonstrated for high-rate lithium-ion batteries. The hybrids can be facilely prepared via in situ introduction of GQDs during the process LTO preparation, which enables a uniform dispersion of GQDs within LTO. This method is convenient, rapid, and can be easily scaled-up. The introduction of 0.05 wt.% GQDs can greatly enhance the electrochemical performance of the electrodes. The electrodes with 0.05 wt.% GQDs deliver a specific discharge capacity of 185, 181 and 179 mAh g-1 at 5, 10, and 20 C, respectively. The performance enhancement is suggested to be due to the synergistic interactions between LTO and GQDs. The strategy as well as as-designed structures of LTO/GQDs show potentials for application as high-rate anode materials in LIBs application.

16.
J Am Chem Soc ; 143(36): 14502-14510, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34476949

RESUMO

The development of light-responsive chemical systems often relies on the rational design and suitable incorporation of molecular photoswitches such as azobenzenes. Linking a photoswitch core with another π-conjugated molecular entity may give rise to intramolecular electronic coupling, which can dramatically impair the photoswitch function. Decoupling strategies have been developed based on additionally inserting a linker that can disrupt the through-bond electronic communication. Here we show that 1,2,3-triazole-a commonly used decoupling spacer-can be directly merged into the azoswitch core to construct a class of "self-decoupling" azoswitches called (hetero)arylazo-1,2,3-triazoles. Such azotriazole photoswitches are easily accessed and modularly functionalized by click chemistry. Their photoswitch property can be optimized by rational design of the substituent groups or heteroaryl rings, allowing (near-)quantitative E⇆Z photoisomerization yields and tunable Z-isomer thermal half-lives from days to years. Combined experimental and theoretical results demonstrate that the electronic structure of the photoswitch core is not substantially affected by various substituents attached to the 1,2,3-triazole unit, benefiting from its cross-conjugated nature. The combination of clickable synthesis, tunable photoswitch property, and self-decoupling ability makes (hetero)arylazo-1,2,3-triazoles intriguing molecular tools in developing photoresponsive systems with desired performance.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34469311

RESUMO

Spectral clustering is a well-known clustering algorithm for unsupervised learning, and its improved algorithms have been successfully adapted for many real-world applications. However, traditional spectral clustering algorithms are still facing many challenges to the task of unsupervised learning for large-scale datasets because of the complexity and cost of affinity matrix construction and the eigen-decomposition of the Laplacian matrix. From this perspective, we are looking forward to finding a more efficient and effective way by adaptive neighbor assignments for affinity matrix construction to address the above limitation of spectral clustering. It tries to learn an affinity matrix from the view of global data distribution. Meanwhile, we propose a deep learning framework with fully connected layers to learn a mapping function for the purpose of replacing the traditional eigen-decomposition of the Laplacian matrix. Extensive experimental results have illustrated the competitiveness of the proposed algorithm. It is significantly superior to the existing clustering algorithms in the experiments of both toy datasets and real-world datasets.

18.
Thorac Cancer ; 12(20): 2680-2690, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34498383

RESUMO

INTRODUCTION: Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. METHODS: One hundred and thirteen patients with lung cancer and 99 age-matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony-stimulating factors were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction in antitumor NK cells (p < 0.0001) and an increase in the protumor MDSCs (p < 0.0001) were observed in the lung cancer patients compared with the controls. Monocyte counts were significantly higher in lung cancer patients with histories of smoking (p < 0.05) or drinking (p < 0.01) than in patients with no relevant history or healthy controls. The number of neutrophils and the neutrophil-to-lymphocyte ratio (NLR) were particularly higher in patients with liver metastasis (p < 0.01) compared with no metastasis patients or healthy controls. Levels of the monocyte-derived cytokine interleukin-6 (p < 0.05), granulocyte colony-stimulating factor (G-CSF) (p < 0.0001), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.0001) were higher in patients than in controls. G-CSF levels decreased during the remission phase (p < 0.05), and positively correlated with carbohydrate antigen 19-9 (p < 0.05) and gene mutation (p < 0.05). CONCLUSION: Monocyte and neutrophil counts were higher in peripheral blood in lung cancer patients than in controls, especially when patients had histories of smoking, drinking, and liver metastasis. Serum levels of G-CSF and GM-CSF were higher in lung cancer patients, and G-CSF levels positively correlated with disease severity.

19.
FEBS Open Bio ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523252

RESUMO

Loss-of-function variants of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of developing Alzheimer's disease (AD). The mechanism through which TREM2 contributes to the disease (TREM2 activation vs inactivation) is largely unknown. Here, we analyzed changes in a gene set downstream of TREM2 to determine whether TREM2 signaling is modified by AD progression. We generated an anti-human TREM2 agonistic antibody and defined TREM2 activation in terms of the downstream expression changes induced by this antibody in microglia developed from human induced pluripotent stem cells (iPSC). Differentially expressed genes (DEGs) following TREM2 activation were compared with the gene set extracted from microglial single nuclear RNA sequencing data of patients with AD, using gene set enrichment analysis. We isolated an anti-TREM2-specific agonistic antibody, Hyb87, from anti-human TREM2 antibodies generated using binding and agonism assays, which helped us identify 300 upregulated and 251 downregulated DEGs. Pathway enrichment analysis suggested that TREM2 activation may be associated with Th2-related pathways. TREM2 activation was lower in AD microglia than in microglia from healthy subjects or patients with mild cognitive impairment. TREM2 activation also showed a significant negative correlation with disease progression. Pathway enrichment analysis of DEGs controlled by TREM2 activity indicated that TREM2 activation in AD may lead to anti-apoptotic signaling, immune response, and cytoskeletal changes in the microglia. We showed that TREM2 activation decreases with AD progression, in support of a protective role of TREM2 activation in AD. In addition, the agonistic anti-TREM2 antibody can be used to identify TREM2 activation state in AD microglia.

20.
BMC Plant Biol ; 21(1): 438, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583634

RESUMO

BACKGROUND: Chlorophyll (Chl) is a vital photosynthetic pigment involved in capturing light energy and energy conversion. In this study, the color conversion of inner-leaves from green to yellow in the new wucai (Brassica campestris L.) cultivar W7-2 was detected under low temperature. The W7-2 displayed a normal green leaf phenotype at the seedling stage, but the inner leaves gradually turned yellow when the temperature was decreased to 10 °C/2 °C (day/night), This study facilitates us to understand the physiological and molecular mechanisms underlying leaf color changes in response to low temperature. RESULTS: A comparative leaf transcriptome analysis of W7-2 under low temperature treatment was performed on three stages (before, during and after leaf color change) with leaves that did not change color under normal temperature at the same period as a control. A total of 67,826 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis revealed that the DEGs were mainly enriched in porphyrin and Chl metabolism, carotenoids metabolism, photosynthesis, and circadian rhythm. In the porphyrin and chlorophyll metabolic pathways, the expression of several genes was reduced [i.e. magnesium chelatase subunit H (CHLH)] under low temperature. Almost all genes [i.e. phytoene synthase (PSY)] in the carotenoids (Car) biosynthesis pathway were downregulated under low temperature. The genes associated with photosynthesis [i.e. photosystem II oxygen-evolving enhancer protein 1 (PsbO)] were also downregulated under LT. Our study also showed that elongated hypocotyl5 (HY5), which participates in circadian rhythm, and the metabolism of Chl and Car, is responsible for the regulation of leaf color change and cold tolerance in W7-2. CONCLUSIONS: The color of inner-leaves was changed from green to yellow under low temperature in temperature-sensitive mutant W7-2. Physiological, biochemical and transcriptomic studies showed that HY5 transcription factor and the downstream genes such as CHLH and PSY, which regulate the accumulation of different pigments, are required for the modulation of leaf color change in wucai under low temperature.

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