To investigate the characteristics of mutation myocilin proteins and glaucoma pathological phenotype in transgenic mice with full-length human Pro370Leu mutant myocilin gene (Tg-
MYOC
P370L
). Tg-
...MYOC
P370L
mice were established using the CRISPR/Cas9 system. Long-term intraocular pressure (IOP) was measured, myocilin protein expressions in anterior chamber angle, retina, optic nerve tissues and aqueous humor were detected by western blot. RBPMS, myocilin, Iba-1 and GFAP expression were visualized by immunofluorescence. H&E staining was applied to assess the ocular angle and retinal morphology. Aqueous humor dynamics were visualized by Gadolinium magnetic resonance imaging (Gd-MRI). TUNEL assay was used to evaluate the specific cell apoptosis in trabecular meshwork and retina. Optomotor and electroretinography tests were employed to evaluate the visual function in Tg-
MYOC
P370L
and wild-type (WT) mice. Homozygous myocilin mutation at position 503 (C > T) was identified by PCR and sequencing in Tg-
MYOC
P370L
mice. Myocilin protein expression was overexpressed in eye tissues of Tg-
MYOC
P370L
mice with reduced myocilin secretion in aqueous humor. H&E staining showed normal histological morphology of anterior chamber angle whereas decreased thickness and nuclei in ganglion cell layer were found (
P
< 0.05). Gd signals were significantly increased in the anterior chamber of Tg-
MYOC
P370L
compared with WT eyes (
P
< 0.05). IOP was elevated in Tg-
MYOC
P370L
mice starting at 5 months of age, with significant RGC loss (
P
< 0.05). Upregulation of caspase-3 and caspase-9 expressions and increased TUNEL-positive cells were found in eyes of Tg-
MYOC
P370L
mice. Excessive activation of retinal glial cells and impaired visual function were detected in Tg-
MYOC
P370L
mice. Tg-
MYOC
P370L
mice can induce the phenotype of open-angle glaucoma, featured as IOP elevation, activated retinal glial cells, loss of RGCs and impaired visual function. These pathologic changes may arise from the abnormal mutant myocilin protein accumulation in the trabecular meshwork and injured aqueous humor drainage. Therefore, Tg-
MYOC
P370L
mice model can serve as an effective animal model for glaucoma research, especially for glaucoma-associated myocilin mutation studies.
Synthesis of nanocomposites containing silver nanoparticles (AgNPs) has drawn growing interest owing to their antimicrobial activity and tuneable physicochemical properties. In this study, we report ...the surface modification of microfibrillated cellulose (MFC) with bio-inspired polydopamine (PDA) followed by in-situ growth and immobilization of AgNPs. The resultant AgNPs-PDA-MFC nanocomposites were characterized by UV–Vis spectrophotometry, scanning electron microscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and X-ray diffraction. The results showed that crystalline face-centered cubic AgNPs with a mean diameter of 19.1 nm were randomly and firmly immobilized on MFC. The attenuated total reflection Fourier transform infrared analysis results confirmed the formation of AgNPs, and the content of silver in AgNPs-PDA-MFC was determined by thermogravimetry. The aqueous suspension of AgNPs-PDA-MFC was stable during 30 days of storage. Antibacterial activity of the AgNPs-PDA-MFC nanocomposites was evaluated with
Escherichia coli
and
Staphylococcus aureus.
Importantly, AgNPs-PDA-MFC exhibited excellent long-term antibacterial activity. This was ascribed to the extremely slow but sustained release of silver from the AgNPs-PDA-MFC (0.56% in 14 days). Furthermore, the application of AgNPs-PDA-MFC as coating and filling agents was preliminarily evaluated. This study suggests that the AgNPs-PDA-MFC nanocomposites with long-term antibacterial performance provide a promising solution for fighting against pathogenic bacteria.
Graphic abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease without cure or effective treatment. This study explores whether the yeast internal NADH-quinone oxidoreductase (NDI1) can ...functionally replace the defective mammalian mitochondrial complex I, which may provide a gene therapy strategy for treating sporadic PD caused by mitochondrial complex I dysfunction.
Recombinant lentivirus expressing NDI1 was transduced into SH-SY5Y cells, or recombinant adeno-associated virus type 5 expressing NDI1 was transduced into the right substantia nigra pars compacta (SNpc) of mouse. PD cell and mouse models were established by rotenone treatment. The therapeutic effects of NDI1 on rotenone-induced PD models in vitro and vivo were assessed in neurobehavior, neuropathology, and mitochondrial functions, by using the apomorphine-induced rotation test, immunohistochemistry, immunofluorescence, western blot, complex I enzyme activity determination, oxygen consumption detection, ATP content determination and ROS measurement.
NDI1 was expressed and localized in mitochondria in SH-SY5Y cells. NDI1 resisted rotenone-induced changes in cell morphology, loss of cell viability, accumulation of α-synuclein and pS129 α-synuclein, mitochondrial ROS production and mitochondria-mediated apoptosis. The basal and maximal oxygen consumption, mitochondrial coupling efficiency, basal and oligomycin-sensitive ATP and complex I activity in cell model were significantly increased in rotenone + NDI1 group compared to rotenone + vector group. NDI1 was efficiently expressed in dopaminergic neurons in the right SNpc without obvious adverse effects. The rotation number to the right side (NDI1-treated side) was significantly increased compared to that to the left side (untreated side) in mouse model. The number of viable dopaminergic neurons, the expression of tyrosine hydroxylase, total and maximal oxygen consumption, mitochondrial coupling efficiency and complex I enzyme activity in right substantia nigra, and the content of dopamine in right striatum were significantly increased in rotenone + NDI1 group compared to rotenone + vector group.
Yeast NDI1 can rescue the defect of oxidative phosphorylation in rotenone-induced PD cell and mouse models, and ameliorate neurobehavioral and neuropathological damages. The results may provide a basis for the yeast NDI1 gene therapy of sporadic PD caused by mitochondrial complex I dysfunction.
SARS-CoV-2, the pathogen of COVID-19, is a worldwide threat to human health and causes a long-term burden on the cardiovascular system. Individuals with pre-existing cardiovascular diseases are at ...higher risk for SARS-CoV-2 infection and tend to have a worse prognosis. However, the relevance and pathogenic mechanisms between COVID-19 and cardiovascular diseases are not yet completely comprehended.
Common differentially expressed genes (DEGs) were obtained in datasets of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2 and myocardial tissues from heart failure patients. Further GO and KEGG pathway analysis, protein-protein interaction (PPI) network construction, hub genes identification, immune microenvironment analysis, and drug candidate predication were performed. Then, an isoproterenol-stimulated myocardial hypertrophy cell model and a transverse aortic constriction-induced mouse heart failure model were employed to validate the expression of hub genes.
A total of 315 up-regulated and 78 down-regulated common DEGs were identified. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive immune inflammation as the most prominent shared features of COVID-19 and cardiovascular diseases. Then, hub DEGs, as well as hub immune-related and mitochondria-related DEGs, were screened. Additionally, nine potential therapeutic agents for COVID-19-related cardiovascular diseases were proposed. Furthermore, the expression patterns of most of the hub genes related to cardiovascular diseases in the validation dataset along with cellular and mouse myocardial damage models, were consistent with the findings of bioinformatics analysis.
The study unveiled the molecular networks and signaling pathways connecting COVID-19 and cardiovascular diseases, which may provide novel targets for intervention of COVID-19-related cardiovascular diseases.
Rice wine, known as yellow wine in China and Japan, possesses considerable nutritional value and holds significant global influence. This study addresses the challenge of preserving rice wine, which ...is prone to rancidity due to its low alcohol content. Conventional storage techniques employing pottery jars often result in substantial spoilage losses. Through rigorous investigation, this research identifies a polarization phenomenon exhibited by degraded rice wine when subjected to high-frequency microwaves(>60GHz), presenting a pioneering method for detecting spoilage, even within sealed containers. Employing a multi-channel microwave radar apparatus, the study delves into the susceptibility of rice wine to electromagnetic waves across various frequencies, uncovering pronounced polarization traits in deteriorated samples within the E-band microwave spectrum. Furthermore, lab-controlled simulations elucidate a direct correlation between physicochemical alterations and high-frequency Radar Cross Section (RCS) signals during the wine’s deterioration process. A novel six-membered Hydrated Cluster hypothesis is proposed, offering insights into the molecular mechanisms underlying this phenomenon. Additionally, dielectric property assessments conducted using vector network analyzers (VNA) reveal noteworthy enhancements in the dielectric constant of deteriorated rice wine, particularly within the high-frequency domain, thereby augmenting detectability. These findings carry implications for refining rice wine preservation techniques and contribute to the advancement of non-destructive testing technologies, enabling the detection of rice wine deterioration or indications thereof, even within sealed vessels.
•A solar air collector with slit-perforated corrugated plate is studied.•Its thermal and flow characteristics are analyzed by mathematic model.•Optimized values of structure and operating parameters ...are put forward.•The collector shows better thermal performance and lower resistance.
In this paper, a solar air collector with slit-perforated corrugated plate is put forward, which is a combination of transpired solar air collector and corrugated packing solar air collector. The slit-perforated corrugated plate can enlarge the heat collection area and reinforce the jet impingement largely. The mathematical model is developed to predict thermal performance of the collector. Simulation results of temperature distribution in the collector are verified by the experimental data with the average bias of 4.8%. The local resistance coefficient of the collector is obtained though experimental results. The effects of key parameters on thermal efficiency are analyzed. It can be found that the height of absorber plate has the largest effect on thermal performance among structure parameters. And when air velocity in the collector increases to 1.14 m/s, effective efficiency can reach the peak, 67.83%. Compared with other transpired solar air collectors, the present solar air collector has better thermal performance and lower resistance. Case study shows that the application of the present solar air collector can produce 820.7 MJ in the heating season, which can save 43.1 kg standard coal and reduce 102.1 kg carbon dioxide emission. Hence, there is application potential for space heating in the cold region.
Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably ...changed genes, and to find out better diagnostic and prognostic markers for HCC.
A systematic review was performed by searching publications indexed in Pubmed from March 1, 2001 to July 1, 2016. Studies that reporting cDNA microarray profiles in HCC, containing both tumor and nontumor data and published in English-language were retrieved. The differentially expressed genes from eligible studies were summarized and ranked according to the frequency. High frequency genes were subjected to survival analyses. The expression and prognostic value of alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) was further evaluated in HCC datasets in Oncomine and an independent HCC tissue array cohort. The role of AGXT in HCC progression was evaluated by proliferation and migration assays in a human HCC cell line.
A total of 43 eligible studies that containing 1917 HCC patients were included, a list of 2022 non redundant abnormally expressed genes in HCC were extracted. The frequencies of reported genes were ranked. We finally obtained a list of only five genes (AGXT; ALDOB; CYP2E1; IGFBP3; TOP2A) that were differentially expressed in tumor and nontumor tissues across studies and were significantly correlated to HCC prognosis. Only AGXT had not been reported in HCC. Reduced expression of AGXT reflected poor differentiation of HCC and predicts poor survival. Knocking down of AGXT enhanced cell proliferation and migration of HCC cell line.
The present study supported the feasibility and necessity of systematic review on discovering new and reliable biomarkers for HCC. We also identified a list of high frequency prognostic genes and emphasized a critical role of AGXT deletion during HCC progression.
•Integrated SHC system driven by PTC and double-effect absorption chiller.•Mathematical model establishment and validation of the whole system.•Comparison of the SHC system and the conventional ...gas-driven absorption heating and cooling system.•Annual performance investigations and assessments of the SHC system.
With the increasing concerns on energy conservation and environmental protection, solar heating and cooling (SHC) system represents an attractive candidate in building sector. In this paper, an integrated SHC system driven by parabolic trough collector (PTC) and double-effect H2O/LiBr absorption chiller was presented. The energy generated by solar collectors was supplied to the absorption chiller during the cooling period, and was directly used for space heating with the integration of plate heat exchanger during the heating period. The mathematical models of the whole system including the collector, the double-effect absorption chiller and the plate heat exchanger were established and were validated by field tests. Based on the proposed models, comparison of the SHC system and the conventional gas-driven absorption heating and cooling system was carried out by case study. The annual performances as well as energetic, economic and environmental assessments of the proposed system were investigated. Results show that, 21.3% of the primary energy consumption and 18.8% of the CO2 emission can be reduced in SHC system. Therefore, the proposed integrated solar heating and cooling system has a promising application prospect in sustainable development in view of its considerable energy saving benefits, potential economic viability and environmental friendly characteristics.
A gridless direction-of-arrival (DOA) estimation algorithm with unsupervised deep learning is proposed to eliminate the influence of the spatial angle discretization on the estimation results and the ...deep neural network's reliance on labels in the training dataset. This algorithm is inspired by the atomic norm minimization (ANM) algorithm and unsupervised deep learning, and a loss function is designed to solve the ANM problem in the unsupervised deep learning framework. The proposed algorithm can address the grid mismatch issue and be more robust to the training dataset, since it no longer depends on the spatial angle discrete grid and labels in the training dataset. Simulation results show that the proposed algorithm is state of the art when compared with the other advanced algorithms currently in use.
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