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Precise distance metrology and measurements play an important role in many fields of scientific research and industrial manufacture. Dual-comb laser ranging combines sub-wavelength ranging precision, large non-ambiguity range, and high update rate, making it the most promising candidate in precise distance metrology and measurements. However, previous demonstrations of dual-comb ranging suffer from short working distances, limited by the decoherence of lasers in interferometric schemes or by the low sensitivity of the photodetectors in response to the sparse echo photons. Here, we propose and demonstrate time-of-flight laser ranging with dual-comb nonlinear asynchronous optical sampling and photon counting by a fractal superconducting nanowire single-photon detector, achieving ranging precision of 6.2 micrometers with an acquisition time of 100 ms and 0.9 micrometers with an acquisition time of 1 s in measuring the distance of an outdoor target approximately 298 m away.
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BACKGROUND AND AIM: The dysbiosis of gut microbiota has been reported in acute pancreatitis. However, the direction and magnitude between host microbiota and pancreas remains to be established. This study investigated the association between gut microbiota and acute pancreatitis using Mendelian randomization (MR) methods. METHODS: Summary statistics of gut microbiota abundance and acute pancreatitis were extracted from genome-wide association studies (GWAS). The two-sample bidirectional MR design was employed to assess genetic association between the microbiota and pancreatitis, followed by a comprehensive sensitivity analysis to verify the robustness of the results. RESULTS: Seven microbiota taxa have been identified as significantly associated with the development of pancreatitis. Host genetic-driven order Bacteroidales and class Bacteroidia are associated with an increased risk of pancreatitis. The genera Coprococcus and Eubacterium fissicatena group also exhibit a positive effect on the development of pancreatitis, while the genera Prevotella, Ruminiclostridium, and Ruminococcaceae act as protective factors against pancreatitis. In contrast, acute pancreatitis was positively correlated with phylum Proteobacteria and genus Lachnospiraceae and negatively correlated with genus Holdemania. CONCLUSIONS: The bidirectional relationship between gut microbiota and acute pancreatitis suggests a critical role for host-microbiota crosstalk in the development of the disease. Targeted modulation of specific gut microbiota enables the prevention and treatment of acute pancreatitis.
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BACKGROUND: Mobility limitation-the loss of exercise capacity or independent living ability-is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled "A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)" to explore the effect of the MDT decision-making intervention for mobility limitation. METHODS: The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form - 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. CONCLUSION: Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. TRIAL REGISTRATION: ChiCTR, ChiCTR2200056756, Registered 19 February 2022.
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Atividades Cotidianas , Fragilidade , Humanos , Idoso , Limitação da Mobilidade , Qualidade de Vida , Exercício Físico , Avaliação Geriátrica/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Three-dimensional surface information acquisition of specular objects plays an important role in the fields of automobile industry, aerospace, cultural relic protection, intelligent robotics, equipment manufacturing, and so on. Most of the existing specular surface measurement methods are based on focused sinusoidal fringe patterns, so there are certain requirements for the range of the depth of field (DOF) of the camera on the focus position. However, for many specular surfaces with a large gradient, the tested objects may not always be in the DOF of the camera, so sinusoidal fringe patterns are defocused to be vulnerable to the noise. In this Letter, a new infrared phase measuring deflectometry (PMD) based on defocused binary fringe is proposed that combines a binary fringe defocusing technique and direct PMD. The measurement principle and the corresponding system calibration method are described. The feasibility and measurement accuracy of fringe defocus in specular measurement are studied in principle. The experimental results on several specular objects show that the proposed method can effectively measure specular surfaces out of the DOF of the camera.
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Absolute distance measurements based on femtosecond lasers have been extensively studied for precision metrology and advanced manufacturing, with the advantages of traceability, high speed, and nanometer precision. However, in previous studies, the dual femtosecond laser ranging system showed limitations such as system complexity, lower integration, dead zone problems in single optical path detection, and high requirements for laser coherence. It is challenging to achieve a high degree of integration and large-scale continuous measurements using femtosecond lasers, ineluctably limiting practical applications in engineering fields. Here, based on the free-running dual femtosecond lasers and the nonlinear asynchronous optical sampling method, we design a highly integrated absolute distance meter. In particular, the dead zone problem is solved by the polarization multiplexing technique, and the digital control system and signal processing system are completed by the Field Programmable Gate Array (FPGA). The absolute distance meter enables rapid, continuous, and accurate measurements over a considerable range without dead zones, which paves a promising way for the integration, instrumentation, and industrial applications of femtosecond laser ranging systems.
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BACKGROUND: Our study aimed to investigate the Hub genes and their prognostic value in colorectal cancer (CRC) via bioinformatics analysis. METHODS: The data set of colorectal cancer was downloaded from the GEO database (GSE21510, GSE110224 and GSE74602) for differential expression analysis using the GEO2R tool. Hub genes were screened by protein-protein interaction (PPI) comprehensive analysis. GEPIA was used to verify the expression of Hub genes and evaluate its prognostic value. The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database. The cBioPortal was used to analyze the type and frequency of Hub gene mutations, and the effects of mutation on the patients' prognosis. The TIMER database was used to study the correlation between Hub genes and immune infiltration in CRC. Gene set enrichment analysis (GSEA) was used to explore the biological function and signal pathway of the Hub genes and corresponding co-expressed genes. RESULTS: We identified 346 differentially expressed genes (DEGs), including 117 upregulated and 229 downregulated. Four Hub genes (AURKA, CCNB1, EXO1 and CCNA2) were selected by survival analysis and differential expression validation. The protein and mRNA expression levels of AURKA, CCNB1, EXO1 and CCNA2 were higher in CRC tissues than in adjacent tissues. There were varying degrees of immune cell infiltration and gene mutation of Hub genes, especially B cells and CD8+ T cells. The results of GSEA showed that Hub genes and their co-expressed genes mainly participated in chromosome segregation, DNA replication, translational elongation and cell cycle. CONCLUSION: Overexpression of AURKA, CCNB1, CCNA2 and EXO1 had a better prognosis for CRC and this effect was correlation with gene mutation and infiltration of immune cells.
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Biomarcadores Tumorais , Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Mapas de Interação de Proteínas , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Biologia Computacional/métodos , Prognóstico , Mapas de Interação de Proteínas/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Ciclina B1/genética , Ciclina A2/genética , Exodesoxirribonucleases/genética , Mutação , Aurora Quinase A/genética , Redes Reguladoras de Genes , Proteínas de Ligação a Poli-ADP-Ribose/genética , Bases de Dados Genéticas , Enzimas Reparadoras do DNARESUMO
Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.
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Proteína 5 Relacionada à Autofagia , Linfócitos T CD4-Positivos , Disfunção Cognitiva , Humanos , Cognição , Disfunção Cognitiva/etiologia , Seguimentos , Linfócitos T Reguladores , Células Th1 , Células Th17 , Células Th2 , Proteína 5 Relacionada à Autofagia/metabolismoRESUMO
BACKGROUND: Glutathione S-transferases (GSTs) are a superfamily of multifunctional enzymes in living organisms with metabolic and detoxification functions, which can detoxify exogenous and endogenous compounds and thereby reduce the damage caused by toxic substances to the body. Ticks are obligate blood-sucking ectoparasites that can transmit various pathogens, and the characterization of tick-derived GSTs may help improve current understanding of the molecular mechanism of tick resistance to insecticides. In this study, a novel GST gene, named HrGSTm1, was identified from Hyalomma rufipes. METHODS: Sequence analysis was performed by using bioinformatics techniques. A prokaryotic expression system was used to obtain the recombinant expression protein rHrGSTm1. Detection of spatiotemporal expression patterns of target genes and their response to the toxicity of cyhalothrin on female H. rufipes was performed by using a quantitative PCR platform. The optimal enzymological parameters of rHrGSTm1 using glutathione as substrate were calculated. The antioxidant capacity of the recombinant protein was evaluated by DPPH⢠(1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl). Knockdown of the HrGSTm1 genes through RNA interference was used to analyze their effects on the physiological parameters of ticks. The changes in HrGSTm1 messenger RNA expression patterns under cypermethrin stress were analyzed. RESULTS: The complementary DNA sequence of HrGSTm1 contained a 672-bp open reading frame, which potentially encoded 223 amino acids. The predicted molecular weight was 25.62 kDa, and the isoelectric point 8.22. HrGSTm1 is a Mu-class GST, belonging to the cytoplasmic GSTs with no signal peptide observed. The Vmax and Km of rHrGSTm1 were 3.367 ± 0.81 uM and 2.208 ± 0.76 uM, respectively, and its activities were dependent on different temperatures and pH conditions; the scavenging rate of rHrGSTm1 to DPPH⢠reached 76.4% at 1.25 mg/ml. Variable expressions of HrGSTm1 were observed under various treatment periods and in different tissues, with the highest appearing in eggs (analysis of variance [ANOVA], F(2, 9) = 279.9, P < 0.0001) and Malpighian tubules (ANOVA, F(3, 12) = 290.5, P < 0.0001). After knockdown of HrGSTm1, compared with the control group, the mortality in the treatment group was increased by 16.7%, the average oviposition rate decreased by 33.9%, the average engorged body weight decreased by 287.38 mg and egg weight decreased by 127.46 mg, although only the engorged body weight was significantly different (t-test, t(44) = 2.886, P = 0.006). After exposure to three sublethal concentrations (LC05, LC10, LC50) of cyhalothrin, the expression level of HrGSTm1 in the midgut, ovary and salivary gland was upregulated, whereas in Malpighian tubules, it showed a trend of upregulation at first and then downregulation, implying different functions during the detoxification in different tissues. CONCLUSIONS: In this study, a novel GST of the Mu-class was successfully isolated from H. rufipes and systematically subjected to bioinformatic analysis and recombination identification. The variation trend of HrGSTm1 expression level in different tissues suggests that the gene has different detoxification functions in different tissues. The potential function of this gene was analyzed to provide basic research for further investigation of its detoxification mechanism.
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Inseticidas , Ixodidae , Carrapatos , Feminino , Animais , Glutationa Transferase/metabolismo , Inseticidas/toxicidade , Ixodidae/genética , Ixodidae/metabolismo , Carrapatos/metabolismo , Proteínas Recombinantes/genética , Glutationa , Peso CorporalRESUMO
Schistosoma japonicum infection is an important public health problem and the S. japonicum infection is associated with a variety of diseases, including colorectal cancer. We collected the paraffin samples of CRC patients with or without S. japonicum infection according to standard procedures. Data-Independent Acquisition was used to identify differentially expressed proteins (DEPs), protein-protein interaction (PPI) network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression) were used to identify candidate genes for diagnosing CRC with S. japonicum infection. To assess the diagnostic value, the nomogram and receiver operating characteristic (ROC) curve were developed. A total of 115 DEPs were screened, the DEPs that were discovered were mostly related with biological process in generation of precursor metabolites and energy,energy derivation by oxidation of organic compounds, carboxylic acid metabolic process, oxoacid metabolic process, cellular respiration aerobic respiration according to the analyses. Enrichment analysis showed that these compounds might regulate oxidoreductase activity, transporter activity, transmembrane transporter activity, ion transmembrane transporter activity and inorganic molecular entity transmembrane transporter activity. Following the development of PPI network and LASSO, 13 genes (hsd17b4, h2ac4, hla-c, pc, epx, rpia, tor1aip1, mindy1, dpysl5, nucks1, cnot2, ndufa13 and dnm3) were filtered, and 3 candidate hub genes were chosen for nomogram building and diagnostic value evaluation after machine learning. The nomogram and all 3 candidate hub genes (hsd17b4, rpia and cnot2) had high diagnostic values (area under the curve is 0.9556). The results of our study indicate that the combination of hsd17b4, rpia, and cnot2 may become a predictive model for the occurrence of CRC in combination with S. japonicum infection. This study also provides new clues for the mechanism research of S. japonicum infection and CRC.
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Coinfecção , Neoplasias Colorretais , Schistosoma japonicum , Esquistossomose Japônica , Humanos , Animais , Proteômica , Biologia Computacional , Aprendizado de Máquina , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genéticaRESUMO
BACKGROUND: The improper land utilization has brought tremendous pressure on the surface water of the Aral Sea Region in the past decades. It was seriously hindered for construction of the Green Silk Road Economic Belt by the fragile environment. Therefore, it is of great necessity for environmental protection and social development to monitor the change of surface water in the Aral Sea Region. METHODS: In this study, LandTrendr algorithm was used on Landsat time-series data to characterize the change in farmland on the Google Earth Engine platform. Based on multi-source data, the water area changes of the Aral Sea were extracted based on the Google Earth Engine, and the mean method was utilized to extract the changes in water level and water storage. Finally, a water-farmland coupling degree model was utilized to evaluate the impact of farmland changes on the surface water in the Aral Sea Region. RESULTS: As a result, the change of farmland is as follows: the farmland area of the Aral Sea Region has abandoned 3,129 km2 from 1987 to 2019, with overall accuracy of 85.3%. The farmland change had increased the drainage downstream of the Amu Darya River and the Syr Darya River. It has led area of the Aral Sea to decrease each year continuously. The area of the Aral Sea shrank by 1,606.36 km2 per year from 1987 to 2019. Furthermore, Aral Sea's water level decreased by 0.13 m per year from 2003 to 2009. The amount of water storage in the Aral Sea Region also showed a downward trend from 2002 to 2016. There was a high-quality coupling coordination 0.903 relationship between surface water and farmland. It will increase the burden of water for people's normal daily life by the water loss resources caused by abandoned farmland. This study emphasized threat of unreasonable farmland management to surface water of the Aral Sea Region. The findings contributed for decision makers to formulating effective reasonable policies to protect surface water and use land of the Aral Sea Region. Meanwhile, the application of coupling degree model can provide a new method for studying the connection of independent systems in the farmland, water, environment and more.
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Água do Mar , Água , Humanos , Fazendas , Conservação dos Recursos Naturais , RiosRESUMO
BACKGROUND: The protein ferritin, which plays an important role in the maintenance of iron homeostasis, is indispensable for iron detoxification, resistance to oxidative stress and innate immunity. Ticks, which are obligate blood-sucking ectoparasites, have to deal with a large amount of iron when they take a blood meal. METHODS: Sequence analysis was undertaken using bioinformatics. A recombinant (r) expression vector, rferritin, was constructed for a prokaryotic expression system. A quantitative polymerase chain reaction platform was used to detect the spatial and temporal expression patterns of target genes and their responses to a low temperature environment. Knockdown of the ferritin genes through RNA interference was used to analyze their effects on physiological parameters of ticks. RESULTS: Two ferritin genes, HrFer1 and HrFer2, were cloned from the tick Hyalomma rufipes. Their open reading frames are 519 base pairs (bp) and 573 bp in length, and number of coding amino acids 170 and 190, respectively. The phylogenetic tree showed that HrFer1 and HrFer2 have a close evolutionary relationship with the H subunit of ferritin. In vitro experiments showed that rHrFer1 and rHrFer2 had concentration-dependent iron chelating activity. The relative expression of the two ferritin genes was higher in the ovary and midgut of H. rufipes. RNA interference results demonstrated that HrFer1 and HrFer2 expression had a significant effect on engorged body weight, number of eggs laid, and mortality of H. rufipes, and that HrFer2 also had a significant effect on feeding duration. Furthermore, the relative expression of ferritin decreased significantly in a low temperature environment, suggesting that HrFer1 and HrFer2 play a regulatory role in the cold stress response of H. rufipes. CONCLUSIONS: The results of the present study improve our understanding of the involvement of ferritins in tick blood-feeding.
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Ixodidae , Carrapatos , Aminoácidos/genética , Animais , Feminino , Ferritinas/genética , Ferro/metabolismo , Quelantes de Ferro , Ixodidae/fisiologia , Filogenia , Carrapatos/fisiologiaRESUMO
As obligate blood-feeding ectoparasites, ticks secrete a great diversity of antithrombin molecules during feeding. In this study, a novel antithrombin gene named Doenitin-1 was characterized from the tick Haemaphysalis doenitzi. It has an open reading frame size of 426 bp; it encodes 141 amino acids and has a predicted molecular weight of 15.8 kDa. The fibrinogen coagulation test showed that the time of coagulation was increased significantly with increase in rDoenitin-1 protein concentration, and the activated partial thromboplastin time (APTT) and prothrombin time (PT) assays showed that rDoenitin-1 significantly prolonged the coagulation time of APTT, indicating that rDoenitin-1 has an anticoagulant activity in vitro. In addition, rDoenitin-1 presents a significant inhibitory activity in thrombin and cathepsin G. The hemolysis rate of rDoenitin-1 in healthy human blood cells was 4.25%, and no obvious hemolysis activity was observed. The comparison with other life stages shows that the higher expression occurs in adults, and tissue comparison indicated a higher expression in the midgut. The RNAi results indicated that interference of Doenitin-1 significantly reduced the engorgement rate and egg hatchability of H. doenitzi, and that the engorged body weight was slightly reduced. In conclusion, the results suggested that the novel gene Doenitin-1 functions in blood-feeding of H. doenitzi and performs various functions during feeding and reproduction of H. doenitzi. Doenitin-1 may be a potential vaccine candidate for tick control and for developing new antithrombotic drugs in the future.
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Background: In hospital settings, malnutrition affects 30-50% of aged inpatients and is related to a higher risk of hospital complications and death. This study aims to demonstrate the effectiveness of a tailored optimum nutritional therapy in malnourished, elderly inpatients based on multidisciplinary team recommendations in hopes of decreasing the incidence of deleterious clinical outcomes. Methods and Design: This trial will be a multicenter, open-label, randomized control trial conducted in the geriatric wards of at least five hospitals in five different regions. We aim to include 500 inpatients over the age of 60 with or at risk of malnutrition based on a Mini Nutritional Assessment Short-Form (MNA-SF) score of ≤ 11 points and the Global Leadership Initiative on Malnutrition with an expected length of stay of ≥ 7 days. Eligible inpatients will be randomized into a 1:1 ratio, with one receiving a multidisciplinary team intervention and the other receiving standard medical treatment or care alone. A structured comprehensive assessment of anthropometry, nutritional status, cognition, mood, functional performance, and quality of life will be conducted twice. These assessments will take place on the day of group allocation and 1 year after discharge, and a structured screening assessment for elderly malnutrition will be conducted at 3 and 6 months after discharge using the MNA-SF. The primary outcome will be nutritional status based on changes in MNA-SF scores at 3, 6 months, and 1 year. The secondary outcome will be changes in cognition, mood, functional status, length of hospital stay, and all-cause mortality 1 year after discharge. Discussion: Guided by the concept of interdisciplinary cooperation, this study will establish a multidisciplinary nutrition support team that will develop an innovative intervention strategy that integrates nutritional screenings, evaluations, education, consultation, support, and monitoring. Moreover, nutritional intervention and dietary fortification will be provided to hospitalized elderly patients with or at risk of malnutrition. The nutrition support team will formulate a clinical map for malnutrition in elderly patients with standardized diagnosis and treatment for malnutrition in this population. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2200055331].
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BACKGROUND: Associated with the significant decrease in water resources, natural vegetation degradation has also led to many widespread environmental problems in the Aral Sea Basin. However, few studies have examined long-term vegetation dynamics in the Aral Sea Basin or distinguished between natural vegetation and cultivated land when calculating the fractional vegetation cover. METHODS: Based on the multi-temporal Moderate Resolution Imaging Spectroradiometer, this study examined the natural vegetation coverage by introducing the Linear Spectral Mixture Model to the Google Earth Engine platform, which greatly reduces the experimental time. Further, trend line analysis, Sen trend analysis, and Mann-Kendall trend test methods were employed to explore the characteristics of natural vegetation cover change in the Aral Sea Basin from 2000 to 2018. RESULTS: Analyses of the results suggest three major conclusions. First, the development of irrigated agriculture in the desert area is the main reason for the decrease in downstream water. Second, with the reduction of water, the natural vegetation coverage in the Aral Sea Basin showed an upward trend of 17.77% from 2000 to 2018. Finally, the main driving factor of vegetation cover changes in the Aral Sea Basin is the migration of cultivated land to the desert.
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The present study aimed to investigate the expression of long non-coding HOX transcript antisense RNA (lncRNA-HOTAIR) in the serum of patients with lymph node metastasis of papillary thyroid carcinoma (PTC) and the underlying mechanism. A total of 89 patients with PTC at Beijing Geriatric Hospital were recruited in this study. Based on the results of color Doppler ultrasound examination, the patients were evaluated for cervical lymph node metastases, and were thereby divided into a metastasis-negative group and a metastasis-positive group. Quantitative fluorescent PCR was used to assess the expression of HOTAIR in serum samples. The PTC cell line TPC-1 was randomly divided into a control and siRNA group. The control group was transfected with a nonsense sequence, while the siRNA group was transfected with si-HOTAIR. After transfection, cell proliferation was evaluated using the MTT assay, and cell migration and invasion were assessed using the cell scratch assay and Transwell assay. Expression levels of vimentin, E-cadherin and proteins associated with the Wnt/ß-catenin signaling pathway were assessed using western blot analysis. Based on the results of the ultrasound examination, 53 patients were allocated to the metastasis-negative group, and 36 to the metastasis-positive group. The expression level of lncRNA-HOTAIR was higher in the metastasis-positive group than that in the metastasis-negative group (P<0.05). Compared with the control group, cell proliferation was reduced while cell migration rate and the number of migrating cells were increased in the siRNA group. Compared with the control group, the expression levels of WIF1 and E-cadherin were significantly increased, while the levels of ß-catenin and vimentin were significantly decreased. In conclusion, lncRNA-HOTAIR is overexpressed in the serum of patients with lymph node metastasis of PTC. In vitro experiments showed that HOTAIR promoted the proliferation and metastasis of PTC cells by regulating epithelial-mesenchymal transition (EMT) mediated by the Wnt/catenin pathway. Thus, lncRNA-HOTAIR is proposed as a molecular target for the treatment of lymph node metastasis of PTC.
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The role of peripheral groups (PGs) on dendrimers in the spontaneous higher-level organization of hierarchically assembled nanofibers was investigated in a series of POSS-based dendritic gelators (POSS-Lys-X, X: -Boc, -Cbz, -Fmoc, etc.). We demonstrate that the PGs not only affect the gelation ability in solutions, but also the construction of orderly entangled fibrous supramolecular networks, e.g., "loofah-like" networks. Attributed to the PGs (especially the -Boc group) causing a lower cooperative assembly, the steady state with the lowest potential energy of gelators can be easily achieved by the higher ordering of nanofiber entanglement into superstructures. The -Boc group-containing dendrimers show low molar enthalpy and molar entropy of gelation, which help the construction of unique three-dimensional (3D) "loofah-like" superstructures. In contrast, the high cooperative assembly of the dendrimer (-Cbz as the PG) promotes the gelator into a higher enthalpy gelation process, with a constructed normal fibrous network. Hence, the PGs of POSS-based dendrimers act as the crucial factor in controlling the hierarchical self-assembly via a thermodynamics approach. This research presents new perspectives to explicate the relationships between PGs of dendrimers, supra-architectures and gel performances, which further guide the design of functional supramolecular materials via controllable self-assembly.
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Chirality-induced recognition-promoted molecule-level self-sorting assembly in a two-component supramolecular gel system constructed by two polyhedral oligomeric silsesquioxane (POSS) core-based dendritic gelators with similar geometry and peripheral functionality, which would normally form a homogeneous co-assembled network.
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Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.
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The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2+) OPCs was significantly higher than that in mature CC1+ oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.
Assuntos
Diferenciação Celular/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Oligodendroglia/metabolismo , Remielinização/fisiologia , Fatores de Transcrição/metabolismo , Animais , Doenças Desmielinizantes/induzido quimicamente , Lisofosfatidilcolinas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Células Precursoras de Oligodendrócitos/citologia , Oligodendroglia/citologiaRESUMO
Due to its apparent rate-limiting function, BACE1 (ß-secretase) appears to be a prime target for prevention of amyloid-ß (Aß) generation in brains with Alzheimer's disease (AD). The activity of BACE1 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor binding site of the BACE1 promoter, indicating that PPARγ may be a potential target for AD treatment. Several studies have demonstrated that PPARγ activation is involved in the immunostimulation of amyloid-ß precursor protein processing by nonsteroidal anti-inflammatory drugs (NSAIDs). The present study found that tripchlorolide (T4), with a similar chemical structure to that of NSAIDs, decreased the levels of Aß secreted in N2a-APP695 cells. T4 treatment reduced the mRNA and protein levels of BACE1 and the protein level of sAPPß, a cleaved N-terminal fragment of APP by BACE1. The treatment also translocated PPARγ from cytoplasm to nuclear. Intriguingly, T4, like pioglitazone (a PPARγ agonist), suppressed the BACE1 activity in N2a-APP695 cells, which was attenuated by GW9662 (a PPARγ antagonist). These results indicate that T4 may be a PPARγ agonist to enhance the binding of nuclear PPARγ to the BACE1 promoter, which may in turn inhibit the transcription and translation of BACE1, suppress the activity of BACE1, and ultimately attenuate the generation of Aß. Due to its capability to alter Aß generation and to protect central neural system against the neurotoxicity of Aß, T4 may serve as a promising agent in modulating Aß-related pathology in Alzheimer's disease.