43 research outputs found
Fundamentals of air cleaning technology and its application in cleanrooms
No full textFundamentals of Air Cleaning Technology and Its Application in Cleanrooms sets up the theoretical framework for cleanrooms. New ideas and methods are presented, which include the characteristic index of cleanrooms, uniform and non-uniform distribution characteristics, the minimum sampling volume, a new concept of outdoor air conditioning and the fundamentals of leakage-preventing layers. Written by an author who can look back on major scientific achievements and 50 years of experience in this field, this book offers a concise and accessible introduction to the fundamentals of air cleaning technology and its application. The work is intended for researchers, college teachers, graduates, designers, technicians and corporate R&D personnel in the field of HVAC and air cleaning technology. Zhonglin Xu is a senior research fellow at China Academy of Building Research
Regulation Of Cardiovascular Homeostasis By Autophagy
No full textMacroautophagy (hereafter autophagy) is a fundamental cellular process that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components. Mitophagy refers to the selective removal of damaged mitochondria via autophagy pathway. In addition to utilizing core autophagic machinery components, mitophagy exploits a variety of molecules, such as PTEN-induced putative kinase protein 1 (PINK1) and Parkin, to identify and eliminate damaged or superfluous mitochondria. Dysregulation of autophagy and mitophagy contributes to a variety of human disorders, including cardiovascular diseases, such as atherosclerosis and diabetic cardiomyopathy. Vascular smooth muscle cells (VSMCs) are a major component of the vascular media, and are vital for maintaining vessel homeostasis. Migration of VSMCs from the media to intima occurs during the development of atherosclerosis. Although alterations in autophagy activity have been reported in atherosclerosis, further investigation is required to delineate the mechanism by which autophagy regulates microtubule stability and cell migration. Diabetic cardiomyopathy, which develops in the absence of traditional risk factors, is a major cause of heart failure in Type 2 diabetic patients. Although multiple factors may collectively contribute to the development of diabetic cardiomyopathy, there is an urgent need to determine the role of autophagy in the development of diabetic cardiomyopathy.
This dissertation has explored the role of autophagy and mitophagy in regulating VSMCs migration as well as in the development of diabetic cardiomyopathy, using comprehensive physiological, pathophysiological, molecular, and genetic approaches. We show that activation of autophagy selectively degrades KAT2A/GCN5, a histone acetyltransferase that acetylates α-tubulin in VSMCs, leading to microtubule instability and promotion of VSMC migration. In diabetic heart, defective autophagy and PINK1/Parkin-mediated mitophagy are regulated by bromodomain-containing protein 4 (BRD4), a bromodomain and extra-terminal domain (BET) family of proteins. Administration of JQ1, one of the BET bromodomain inhibitors, restores PINK1/Parkin-mediated mitophagy and prevents high-fat-diet induced diabetic cardiomyopathy. Collectively, our work suggests that autophagy suppression in VSMCs is an important therapeutic target for atherosclerosis and that suppression of BRD4 may be a new therapeutic approach for diabetic cardiomyopathy
Genome-wide association study identifies 12 new genetic loci associated with growth traits in pigs
No full textGrowth traits are among the most important economic traits in pigs and are regulated by polygenes with complex regulatory mechanisms. As the major indicators of growth performance, the backfat thickness (BFT), loin eye area (LEA), and days to 100 kg (D100) traits are commonly used to the genetics improvement in pigs. However, the available genetic markers for these traits are limited. To uncover novel loci and candidate genes associated with growth performance, we collected the phenotypic information of BFT, LEA, and D100 in 1,186 pigs and genotyped all these individuals using the Neogen GGP porcine 80K BeadChip. We performed a genome-wide association study (GWAS) using 4 statistical models, including mixed linear models (MLM), fixed and random model circulating probability unification (FarmCPU), settlement of MLM under progressively exclusive relationships (SUPER), Bayesian-information and linkage-disequilibrium Iteratively nested keyway (Blink), and identified 5, 3, and 6 high-confidence single nucleotide polymorphisms (SNPs) associated with BFT, LEA, and D100, respectively. Variant annotation and quantitative trait locus (QTL) mapping analysis suggested that 6 genes (SKAP2, SATB1, PDE7B, PPP1R16B, WNT3, and WNT9B) were potentially associated with growth performance in pigs. Transcriptome analysis suggested that the expression of Src Kinase Associated Phosphoprotein 2 (SKAP2) was higher in prenatal muscles than in postnatal muscles, and the expression of Phosphodiesterase 7B (PDE7B) continuously increased during the prenatal stages and gradually decreased after birth, implying their potential roles in prenatal skeletal muscle development. Overall, this study provides new candidate loci and genes for the genetic improvement of pigs
Structure and composition study of carbon-doped titanium oxide film combined with first principles
No full textLoran-C ground-wave propagation prediction based on the calibrated two-way NAPE algorithm
No full textA modified MTS proliferation assay for suspended cells to avoid the interference by Hydralazine and beta-Mercaptoethanol
No full textThe 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay is one of the most commonly used tests of cell proliferation. Hydralazine has been reported to interfere with the performance of the MTS assay when used on adherent cells. This study aimed to investigate whether hydralazine interferes with the performance of the MTS assay on suspended cells. THP-1 (a monocytic leukemia cell line) cells were cultured in the presence or absence of hydralazine (0, 10, 50, 100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using the MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established by centrifuging the cells and replacing the test medium with fresh culture medium immediately before the addition of the MTS reagent. Culture of THP-1 cells with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p < 0.001) in the standard MTS assay, whereas both the trypan blue exclusion assay and microscopy suggested no change in cell numbers. Culture of THP-1 cells with 100 and 500 mu m hydralazine for 24 h increased absorbance (p < 0.05) in the standard MTS assay; however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (100 and 500 mu M) increased absorbance in a time- and concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy using THP-1 cells. In addition, the modified MTS assay produced reliable results when K562 and Jurkat cells were incubated with hydralazine or beta-mercaptoethanol (beta ME). In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and beta ME when assessing suspended cells
An improved 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay to overcome the interference of hydralazine
No full textThe MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds
Discovery of Quinazolone Pyridiniums as Potential Broad-Spectrum Antibacterial Agents
No full textThe overprescription of antibiotics in medicine and agriculture has accelerated the development and spread of antibiotic resistance in bacteria, which severely limits the arsenal available to clinicians for treating bacterial infections. This work discovered a new class of heteroarylcyanovinyl quinazolones and quinazolone pyridiniums to surmount the increasingly severe bacterial resistance. Bioactive assays manifested that the highly active compound 19a exhibited strong inhibition against MRSA and Escherichia coli with extremely low MICs of 0.5 μg/mL, being eightfold more active than that of norfloxacin (MICs = 4 μg/mL). The highly active 19a with rapid bactericidal properties displayed imperceptible resistance development trends, negligible hemolytic toxicity, and effective biofilm inhibitory effects. Preliminary explorations on antibacterial mechanisms revealed that compound 19a could cause membrane damage, embed in intracellular DNA to hinder bacterial DNA replication, and induce metabolic dysfunction. Surprisingly, active 19a was found to trigger the conformational change in PBP2a of MRSA to open the active site, which might account for its high inhibition against MRSA. In addition, the little effect of molecule 19a on the production of reactive oxygen species indicated that bacterial death was not caused by oxidative stress. The above comprehensive analyses highlighted the large potential of quinazolone pyridiniums as multitargeting broad-spectrum antibacterial agents
Novel Thiazolylketenyl Quinazolinones as Potential Anti-MRSA Agents and Allosteric Modulator for PBP2a
No full textBacterial infections caused by methicillin-resistant Staphylococcus aureus have seriously threatened public health. There is an urgent need to propose an existing regimen to overcome multidrug resistance of MRSA. A unique class of novel anti-MRSA thiazolylketenyl quinazolinones (TQs) and their analogs were developed. Some synthesized compounds showed good bacteriostatic potency. Especially TQ 4 was found to exhibit excellent inhibition against MRSA with a low MIC of 0.5 μg/mL, which was 8-fold more effective than norfloxacin. The combination of TQ 4 with cefdinir showed stronger antibacterial potency. Further investigation revealed that TQ 4, with low hemolytic toxicity and low drug resistance, was not only able to inhibit biofilm formation but also could reduce MRSA metabolic activity and showed good drug-likeness. Mechanistic explorations revealed that TQ 4 could cause leakage of proteins by disrupting membrane integrity and block DNA replication by intercalated DNA. Furthermore, the synergistic antibacterial effect with cefdinir might be attributed to TQ 4 with the ability to induce PBP2a allosteric regulation of MRSA and further trigger the opening of the active site to promote the binding of cefdinir to the active site, thus inhibiting the expression of PBP2a, thereby overcoming MRSA resistance and significantly enhancing the anti-MRSA activity of cefdinir. A new strategy provided by these findings was that TQ 4, possessing both excellent anti-MRSA activity and allosteric effect of PBP2a, merited further development as a novel class of antibacterial agents to overcome increasingly severe MRSA infections
An in-vitro biomechanical study of different fixation techniques for the extended trochanteric osteotomy in revision THA
No full textBackground: The wire fixation and the cable grip fixation have been developed for the extended trochanteric osteotomy (ETO) in the revision of total hip arthroplasty (THA). Many studies reported the postoperative performance of the patients, but with little quantitative biomechanical comparison of the two fixation systems. Methods: An in-vitro testing approach was designed to record the loosening between the femoral bed and the greater trochanter after fixations. Ten cadaveric femurs were chosen in this study. Each femur underwent the THA, revision by ETO and fixations. The tension to the greater trochanter was from 0 to 500N in vertical and lateral direction, respectively. The translation and rotation of the greater trochanter with respect to the bony bed were captured by an optical tracking system. Results: In the vertical tension tests, the overall translation of the greater trochanter was observed 0.4 mm in the cable fixations and 7.0 mm in the wire fixations. In the lateral tension tests, the overall motion of the greater trochanter was 2.0 mm and 1.2 degrees in the cable fixations, while it was 6.2 mm and 5.3 degrees in the wire fixations. The result was significantly different between the two fixation systems. Conclusions: The stability of the proximal femur after ETO using different fixations in the revision THA was investigated. The cable grip fixation was significantly more stable than the wire fixation.OrthopedicsSCI(E)1ARTICLEnull
