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1.
Methods Mol Biol ; 2386: 157-169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34766271

RESUMO

Digital proximity ligation assay (PLA) detects single protein molecules with a pair of oligonucleotide-conjugated antibodies and digital PCR (dPCR) readout, which allows absolute quantitation of proteins in single cells with high sensitivity. The pipeline also allows simultaneous measurement of protein and mRNA from the same single cell. The sensitivity of the assay has been further improved with implementation of the assay on a microfluidic system, which enables quantitation of rare protein species, with expression level as low as ~3000 protein molecules per cell.

2.
Sci Rep ; 11(1): 21775, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741126

RESUMO

The West Philippine Basin (WPB) has started opening at ~ 58 Ma and ceased spreading at ~ 33 Ma, developing a fast spreading (~ 44 mm/yr half-spreading rate) magmatic episode between 58 and 41 Ma and the second amagmatic episode between 41 and 33 Ma. The occurrence of the first stage of spreading is closely related to the Oki-Daito mantle plume and related Benham Rise (BR) and Urdaneta Plateau (UP) activity. To the east of the Luzon-Okinawa Fracture Zone (LOFZ), BR was the most active volcanism from 48 to 41 Ma. The geomagnetic ages on both sides of the LOFZ have been determined; however, their causal relationship and evolution in the WPB remain unclear. In this study, we performed integrated analyses of multichannel seismic data and swath bathymetry data for the area to the west of the LOFZ. To the west of the LOFZ, the Gagua Rise (GR), is identified by a high residual free-air gravity anomaly, volcanic seamount chains and an overlapping spreading center. The GR is located at magnetic isochrons C20/C22 (50 to 44 Ma) and shows a thick oceanic crust of at least 12.7 km. We first propose an oceanic plateau named Great Benham Rise (GBR) which includes GR, UP and BR. We infer that the GR was a portion of the GBR since ~ 49 Ma and was separated from the GBR at ~ 41 Ma by the right-lateral LOFZ motion. Later, the relict GBR magmatism only continued in the area to the east of the LOFZ. Overall, the GBR dominates the spreading history of the WPB.

3.
Front Psychiatry ; 12: 686711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744812

RESUMO

Background: Depressive symptoms are common in older adults. Developing rapid self-report tools is essential to measure the presence and severity of depressive symptoms in older adults. This study evaluated the psychometric properties of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scale for use in depressed older adults. Methods: A total of 238 depressed older adults were included in the study. The Montgomery-Asberg Depression Rating Scale (MADRS) and the QIDS-SR were administered to assess the severity of depressive symptoms. Cronbach's alpha coefficient, Spearman rank correlations, and principal component analysis were performed to estimate the internal consistency, convergent validity, and factorial structure of the QIDS-SR, respectively. Results: The Cronbach's alpha for the QIDS-SR was acceptable (α = 0.64). Item-total correlation analyses showed that the items of concentration/decision-making, involvement, energy level, and agitation/retardation had high correlation with the QIDS-SR total score (all correlation coefficients ≥0.60). The QIDS-SR total score was significantly correlated with the MADRS total score (r = 0.53, p < 0.001), demonstrating acceptable convergent validity. Factor analysis revealed the unidimensional structure of the QIDS-SR. Conclusions: The QIDS-SR appears to be a reliable and valid self-report scale for estimating the severity of depressive symptoms in depressed older adults.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34753622

RESUMO

Surface ligand engineering is of great importance for the preparation of one-dimensional (1D) CsPbBr3 nanowires for high-performance photodetectors. The traditional long-chain terminated ligands such as oleylamine/oleic acid (C18) used in the preparation of CsPbBr3 nanowires will form an electrically insulating layer on the surface of the nanowires, which hinders the effective transport of charge carriers in optoelectronic devices. In this paper, short-chain ligands, including dodecylamine/dodecanoic acid (C12), octylamine/octanoic acid (C8) and hexylamine/hexanoic acid (C6), are introduced to partially replace long-chain ligands (C18) to successfully prepare various CsPbBr3 nanowires via a solvothermal method. Microstructure characterization indicates that the four kinds of nanowires before/after surface ligand engineering, which are named as C18-CsPbBr3, C12/18-CsPbBr3, C8/18-CsPbBr3 and C6/18-CsPbBr3, all have high aspect ratio and purity. As compared with CsPbBr3 with long-chain terminated ligands, the C8/18-CsPbBr3 and C6/18-CsPbBr3 nanowires with shorter chain ligands exhibit superior photoluminescence (PL) performance and stability under adverse conditions such as ultraviolet irradiation and high temperature. The constructed photodetectors based on C8/18-CsPbBr3 and C6/18-CsPbBr3 nanowires have shown improved performances. This work provides a new idea for the preparation of CsPbBr3 nanowires with high optical properties, stability and charge transport, and the prepared CsPbBr3 nanowires have potential application prospects in optoelectronic devices.

5.
Medicine (Baltimore) ; 100(45): e27739, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766585

RESUMO

ABSTRACT: Chloride intracellular channel (CLIC) proteins are novel Cl-channels with 6 family members (CLIC1-6) that are known to play crucial roles in multiple physiological functions, such as neurological, cardiovascular, pulmonary, and auditory functions, and in various malignancies, including hepatocellular carcinoma (HCC). However, considerable challenges exist in identifying appropriate CLICs as therapeutic target molecules and prognostic biomarkers for HCC because the transformation of soluble or integral membrane protein forms, and specific pharmacological agents (agonists and antagonists) for distinct CLICs remains enigmatic.To address this issue and the possible molecular basis and the signaling networks activated by CLICs in HCC, we examined the transcriptional, promoter methylation, DNA mutation, survival, and immune infiltration data of CLICs in patients with HCC using the ONCOMINE, UALCAN, GEPIA, cBioPortal, and TIMER databases.The data showed that the expression levels of CLIC family members were differed between tumor and normal tissues. High expression levels of CLIC1 and CLIC3 were associated with advanced cancer stage in HCC patients. Low CLIC1 expression was associated with a better overall survival (OS). The DNA methylation levels of the CLIC1-3 and CLIC5-6 promoters in tumor tissue with HCC were significantly lower in HCC tissues than in normal tissues. Patients with CLIC1 alterations had a shorter OS than patients with unaltered CLIC1. Moreover, the expression levels of CLICs correlated with the infiltration of 6 different immune cells (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells).These results indicate that the increased mRNA expression and decreased promoter DNA methylation level of CLICs may play crucial roles in HCC tumorigenesis. The expression of CLIC family members was significantly correlated with the tumor immune status. High CLIC1 and CLIC3 expression levels could serve as biomarkers for identifying advanced-stage HCC. Moreover, a CLIC1 mutation rate of 18% was also observed and CLIC1 genetic alterations were significantly associated with lower OS in HCC patients.

6.
Curr Eye Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766863

RESUMO

PURPOSE: To investigate the anti-inflammatory and anti-fungal role of α-melanocyte stimulating hormone (α-MSH) in Aspergillus Fumigatus (A. fumigatus) keratitis. METHOD: Corneas of C57BL/6 mice were infected with A. Fumigatus. α-MSH (5 ul, 1x10-4mmol/ml) was given by subconjunctival injection from day 1 to day 3 post infection (p.i.). After 3 days p.i., clinical score was recored and HE staining was tested. Fungal load in mice corneas was observed by plate counting. Pro-inflammatory mediators and pattern recognition receptors (PRRs) were detected. The numbers of neutrophils and macrophages were tested by immunofluorescence staining. The role of α-MSH in RAW264.7 cells after A. fumigatus stimulation were evaluated by PCR and Western blot, and MPKA protein levels including total-JNK (T-JNK), phosphorylated-JNK (P-JNK), total-ERK (T-ERK) and phosphorylated-ERK (P-ERK) were tested via Western blot with or without α-MSH treatment. RESULTS: Compared with PBS control group, α-MSH treatment alleviated disease response and decreased clinical score at 3 days p.i. HE staining showed less infiltration in corneal tissue after α-MSH treatment. Plate counting experiment showed that number of viable fungus in corneas of α-MSH treated group was less than control group. mRNA levels of IL-1ß, TNF-α, IL-6, MIP-2, LOX-1, Dectin-1 and iNOS were decreased. Protein levels of IL-1ß, TNF-α, IL-6 and Dectin-1 were decreased. α-MSH treatment also decreased the infiltrating neutrophils and macrophages. The levels of pro-inflammatory cytokines, Dectin-1 and LOX-1 stimulated by A. fumigatus, were also suppressed by pretreatment of α-MSH in RAW264.7 cells. The ratio of P-JNK/T-JNK and P-ERK/T-ERK were down regulated in α-MSH group compared with PBS control group. CONCLUSION: α-MSH alleviates the severity and decreases fungal load of A. fumigatus keratitis in mice. Migration of neutrophils and macrophages are restrained. α-MSH downregulates the expression of dectin-1 and the ratio of P-JNK/T-JNK and P-ERK/T-ERK in A. fumigatus infection.

7.
BMC Neurol ; 21(1): 437, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753429

RESUMO

BACKGROUND: Early identification of massive middle cerebral artery infarction (MCAI) at risk for malignant MCAI (m-MCAI) may be useful in selecting patients for aggressive therapies. The aim of this study was to determine whether CYP metabolites may help to predict impending m-MCAI. METHODS: This is a prospective, two-center observational study in 256 patients with acute massive MCAI. Plasma levels of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids, and dihydroxyeicosatrienoic acids were measured at admission. Brain computed tomography (CT) was performed at admission and repeated between day 3 and 7, or earlier if there was neurological deterioration. The primary outcome was m-MCAI. The m-MCAI was diagnosed when follow-up brain CT detected a more than two-thirds space-occupying MCAI with midline shift, compression of the basal cisterns, and neurological worsening. RESULTS: In total of 256 enrolled patients, 77 (30.1%) patients developed m-MCAI. Among the 77 patients with m-MCAI, 60 (77.9%) patients died during 3 months of stroke onset. 20-HETE level on admission was significantly higher in patients with m-MCAI than those without m-MCAI. There was an increase in the risk of m-MCAI with increase of 20-HETE levels. The third and fourth quartiles of 20-HETE levels were independent predictors of m-MCAI (OR: 2.86; 95% CI: 1.16 - 6.68; P = 0.025, and OR: 4.23; 95% CI: 1.35 - 8.26; P = 0.002, respectively). CONCLUSIONS: Incidence of m-MCAI was high in patients with massive MCAI and the prognosis of m-MCAI is very poor. Elevated plasma 20-HETE may be as a predictor for m-MCAI in acute massive MCAI, and it might useful in clinical practice in therapeutic decision making.


Assuntos
Infarto da Artéria Cerebral Média , Acidente Vascular Cerebral , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Prognóstico , Estudos Prospectivos
8.
Biosci Trends ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759119

RESUMO

In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.

9.
Cell Death Dis ; 12(11): 1081, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775467

RESUMO

Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In the present study, we identified a novel circular RNA, circESRP1, that derived from the ESRP1 gene locus at 8q22.1 exons. Lower expression of circESRP1 was found in clear cell RCC (ccRCC) tissues and cell lines. Besides, circESRP1 expression level showed inversely correlated with the advanced tumor size, TNM stage and distant metastasis of ccRCC. The expression level of circESRP1 exhibited a positive correlation with CTCF protein but negatively correlated with miR-3942 in 79 ccRCC tissues. In vivo experiments, we found that overexpression of circESRP1 effectively repressed xenograft tumor growth and inhibited c-Myc-mediated EMT progression. CircESRP1 acted as a sponge to competitively bind with miR-3942 as confirmed through RNA pull-down, RIP and dual-luciferase reporter assays. Moreover, CTCF, a downstream target of miR-3942, was validated to specifically promote the circESRP1 transcript expression and regulated by circESRP1/miR-3942 pathway to form a positive feedback loop. We also revealed that the circESRP1/miR-3942/CTCF feedback loop regulated the ccRCC cell functions via c-Myc mediated EMT process. This study provides a novel regulatory model of circRNA via forming a positive-feedback loop that perpetuates the circESRP1/miR-3942/CTCF axis, suggesting that this signaling may serve as a novel target for the treatment of ccRCC.

11.
J Bioenerg Biomembr ; 53(6): 703-713, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34729671

RESUMO

Endometrial cancer (EC) is a common gynecological malignant tumor worldwide. It is imperative to study pathogenesis and therapeutic targets for improving the prognosis of EC. The present study aimed to explore the function and mechanism of kinesin family member C1 (KIFC1) in EC. EC tumor and adjacent normal tissues were collected from 68 pairs of patients. The expression of KIFC1 in tissues and EC cells was analyzed by immunohistochemistry, qRT-PCR or western blot. MTT assay was used to test the cell viability. Flow cytometry was used to determine apoptosis and the cell cycle. Glucose uptake, lactate production, ATP contents and lactate dehydrogenase (LDH) activity were evaluated by a glucose metabolism kit. The expression of HMGA1, c-myc and glycolytic genes was assessed using western blot or qRT-PCR. A mouse xenograft model was established in BALB/c mice to detect tumor growth in vivo. KIFC1 was significantly upregulated in EC tumor tissues compared to adjacent normal control tissues. The upregulated expression of KIFC1 was correlated with poor prognosis in patients. Lentiviral-mediated overexpression of KIFC1 observably enhanced cell viability and reduced the apoptotic rate of Ishikawa and HEC-1B cells. Cell cycle progression was also expedited in the KIFC1 vector group. Moreover, overexpression of KIFC1 elevated glucose uptake, lactate production, ATP contents and LDH activity. However, knockdown of KIFC1 by short hairpin RNA (shRNA) showed the reverse effect on cellular functions. In addition, the expression of c-myc, GLUT1, LDHA and HK2 was increased by the KIFC1 vector. Moreover, HMGA1 regulated the expression of c-myc and glycolytic genes. Upregulated HMGA1 could rescue the effect of KIFC1 knockdown on cellular functions and the expression of glycolytic genes. Finally, KIFC1 knockdown inhibits tumor growth in vivo. The upregulation of KIFC1 was correlated with poor prognosis in EC. KIFC1 promoted aerobic glycolysis in endometrial cancer cells by regulating the HMGA1/c-myc pathway. KIFC1 may be a potential target for the diagnosis and therapy of EC.

12.
Clinics (Sao Paulo) ; 76: e3069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755758

RESUMO

OBJECTIVES: This study explored the clinical efficacy of VitalStim electrical stimulation combined with swallowing function training for patients with dysphagia following an acute stroke. METHODS: Seventy-two patients with dysphagia following an acute stroke were admitted to our hospital and were further divided into two groups using prospective research methods. There were 36 cases in each group according to the random number table method. The control group received conventional medical treatment and swallowing function training while the experimental group received conventional medical treatment and VitalStim electrical stimulation combined with swallowing function training. RESULTS: The overall response rate of the experimental group (94.44%) was higher than that of the control group (77.78%), and the difference was statistically significant (p<0.05). Compared with before treatment, the upward and forward movement speeds of the hyoid bone, anterior movement speed, the grading score of the Kubota drinking water test, Caiteng's grading score, serum superoxide dismutase, 5-hydroxytryptamine, and norepinephrine levels, Fugl-Meyer Assessment score, and multiple quality of life scores of the two groups showed improvement after treatment. While the standard swallowing assessment score, serum malondialdehyde level, and National Institutes of Health Stroke Scale score decreased, the aforementioned indices showed a significant improvement in the experimental group (p<0.05). CONCLUSION: The results of this study indicate that VitalStim electrical stimulation combined with swallowing function is effective for treating dysphagia following an acute stroke. It can effectively improve swallowing, neurological, and limb motor functions, reduce complications, promote physical recovery, and improve overall quality of life of patients.

13.
Lipids Health Dis ; 20(1): 167, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823555

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

14.
Ann Palliat Med ; 10(10): 10607-10615, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763508

RESUMO

BACKGROUND: Blood samples indicative of jaundice, lipemia, hemolysis, and others are often encountered in the laboratory, and such features impact greatly on the detection of coagulation items. To understand the anti-interference ability of the magnetic bead method automatic coagulation instrument and the optical method automatic coagulation instrument against jaundice, lipemia, and hemolysis, anti-interference experiments of prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) were conducted using ExC810 (magnetic bead method) and CS5100 (optical method). METHODS: Interference samples were prepared with bilirubin, hemoglobin, and lipids, while control samples were prepared with NaOH and distilled water. The samples contained different values of PT, APTT, TT, and FIB and were detected by magnetic bead method and optical method, respectively. The relative deviation was calculated according to the formula. RESULTS: In the anti-interference experiment of PT, APTT, TT, and FIB (jaundice, lipemia, hemolysis), the deviation between the test results and the control results with the addition of interfering substances tested by ExC810 was lower overall than that of CS5100. However, after the addition of interfering substances, most of the items were not detected by CS5100 in the anti-lipidemia experiment. CONCLUSIONS: When testing coagulation function, the magnetic bead method has better anti-interference recognition of jaundice, lipemia, and hemolysis than the optical method, and its anti-lipemic interference has a particularly obvious advantage.


Assuntos
Coagulação Sanguínea , Fibrinogênio , Testes de Coagulação Sanguínea , Fibrinogênio/análise , Humanos , Fenômenos Magnéticos , Tempo de Tromboplastina Parcial
15.
Appl Opt ; 60(32): 10094-10100, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34807114

RESUMO

A novel, to the best of our knowledge, configuration of a Littrow-Offner spectrometer that is off-axis in both the meridian and sagittal planes is proposed. Through theoretical analysis, the relationship between the distance of each element and the aperture is obtained, and the theoretical basis of the sagittal plane off-axis is given. Extra aberrations are corrected by a spherical lens with a convex grating. An example of design has been presented with an f-number of 4 working in 300-500 nm, according to the theory. Its spectral resolution achieves a 0.1 nm at central wavelength, and its volume decreases by 14.5% compared with the traditional Offner spectrometer.

16.
Opt Express ; 29(22): 36616-36633, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34809069

RESUMO

An advanced Dyson imaging spectrometer in the near ultraviolet-visible-near infrared region was designed, fabricated, and evaluated. A lens with reflective coating on the back surface is applying to replace the traditional lens-reflecting grating combination. The design concept and fabrication and alignment methods as well as the results of evaluations of the proposed spectrometer are described in detail. The advanced imaging spectrometer achieves high resolution in both spectral and spatial direction and low stray light at a high numerical aperture in the working waveband. The performance of this modified porotype is analyzed and evaluated. Results show the spectrometer is well suited for the remote sensing of the ocean color as well as for various agriculture and vegetation-related applications.

17.
Mater Horiz ; 8(1): 78-101, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821291

RESUMO

Compared to traditional drug delivery systems, DNA nanostructure-based drug delivery systems have several advantages including programmable sequences, precise size and shape, high drug payloads, excellent biocompatibility and biodegradability. To date, a wide range of chemotherapeutic drug-DNA hybrid nanostructures have been developed for anti-tumor therapy. In this review, the constructions of various DNA nanostructures for anticancer drug delivery are firstly summarized. Next, the anticancer drug loading methods for DNA nanostructures are presented. Then, the recent applications of chemotherapeutic drug-DNA hybrid nanostructures for drug delivery are highlighted. In the end, the challenges and opportunities of the chemotherapeutic drug-DNA hybrid nanostructure-based delivery system are discussed. The designs of drug-DNA hybrid systems, including the constructions of nanostructures and the strategies for drug loading, largely influence the efficiency of drug delivery. Recent studies have focused on the development of novel drug-DNA hybrid systems to acquire more precise and efficient therapy for various diseases. A systematic review of the design strategies of chemotherapeutic drug-DNA hybrid nanostructures will benefit the innovation and development of the chemotherapeutic drug-based chemotherapy in clinics.

18.
Mol Med ; 27(1): 149, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837956

RESUMO

BACKGROUND: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. METHODS: In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3'-di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. RESULTS: DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. CONCLUSION: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.

19.
Neural Netw ; 145: 331-341, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34801942

RESUMO

Driven by industrial big data and intelligent manufacturing, deep learning approaches have flourished and yielded impressive achievements in the community of machine fault diagnosis. Nevertheless, current diagnosis models trained on a specific dataset seldom work well on other datasets due to the domain discrepancy. Recently, adversarial domain adaptation-based approaches have become an emerging and compelling tool to address this issue. Nonetheless, existing methods still have a shortcoming since they cannot guarantee sufficient feature similarity between the source domain and the target domain after adaptation, resulting in unguaranteed performance. To this end, a Cycle-consistent Adversarial Adaptation Network (CAAN) is advanced to realize more effective fault diagnosis of machinery. In CAAN, specifically, an adversarial game formed by the feature extractor and the domain discriminator is constructed to induce transferable feature learning. Meanwhile, the feature translators and discriminators between source and target domains are further designed to build a more comprehensive cycle-consistent generative adversarial constrain, which can more reliably ensure domain-invariant and class-separate characteristics of learned features. Extensive experiments constructed on three datasets from different mechanical systems demonstrate the effectiveness and superiority of CAAN.

20.
Adv Mater ; : e2103980, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775641

RESUMO

Complete resection of IDH1 (R132H) glioma is infeasible and the classic post-surgical chemo/radiotherapy suffers from high recurrence and low survival rate. IDH1 (R132H) cells are sensitive to low concentration of glucose and high concentration of reactive oxygen species (ROS) due to inherent metabolism reprograming. Hence, a starvation/chemodynamic therapeutic gel was developed to combat residual IDH1 (R132H) tumor cells after surgery. Briefly, glucose oxidase (GOx) is mineralized with manganese-doped calcium phosphate to form GOx@MnCaP nanoparticles, which were encapsulated into the fibrin gel (GOx@MnCaP@fibrin). After spraying gel in the surgical cavity, GOx catalyzed the oxidation of glucose in residual IDH1 (R132H) cells and produced H2 O2 . The generated H2 O2 was further converted into highly lethal hydroxyl radicals (•OH) by Mn2+ mediated Fenton-like reaction to further kill the residual IDH1 (R132H) cells. The as-prepared starvation/chemodynamic therapeutic gel showed much higher therapeutic efficacy towards IDH1 (R132H) cells than IDH1 (WT) cells, and achieved long-term survival. This article is protected by copyright. All rights reserved.

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