mSin3A is a core component of a large multiprotein corepressor complex with associated histone deacetylase (HDAC) enzymatic activity. Physical interactions of mSin3A with many sequence-specific ...transcription factors has linked the mSin3A corepressor complex to the regulation of diverse signaling pathways and associated biological processes. To dissect the complex nature of mSin3A's actions, we monitored the impact of conditional mSin3A deletion on the developmental, cell biological, and transcriptional levels. mSin3A was shown to play an essential role in early embryonic development and in the proliferation and survival of primary, immortalized, and transformed cells. Genetic and biochemical analyses established a role for mSin3A/HDAC in p53 deacetylation and activation, although genetic deletion of p53 was not sufficient to attenuate the mSin3A null cell lethal phenotype. Consistent with mSin3A's broad biological activities beyond regulation of the p53 pathway, time-course gene expression profiling following mSin3A deletion revealed deregulation of genes involved in cell cycle regulation, DNA replication, DNA repair, apoptosis, chromatin modifications, and mitochondrial metabolism. Computational analysis of the mSin3A transcriptome using a knowledge-based database revealed several nodal points through which mSin3A influences gene expression, including the Myc-Mad, E2F, and p53 transcriptional networks. Further validation of these nodes derived from in silico promoter analysis showing enrichment for Myc-Mad, E2F, and p53 cis-regulatory elements in regulatory regions of up-regulated genes following mSin3A depletion. Significantly, in silico promoter analyses also revealed specific cis-regulatory elements binding the transcriptional activator Stat and the ISWI ATP-dependent nucleosome remodeling factor Falz, thereby expanding further the mSin3A network of regulatory factors. Together, these integrated genetic, biochemical, and computational studies demonstrate the involvement of mSin3A in the regulation of diverse pathways governing many aspects of normal and neoplastic growth and survival and provide an experimental framework for the analysis of essential genes with diverse biological functions.
Arterial dissection is caused by intima damage and blood flow into the vascular wall, resulting in the separation of the intima and middle layer, intramural hematoma formation, and subsequently ...stenosis, occlusion, or aneurysm. A 68-year-old woman with bilateral common carotid artery dissection (CAD) caused by a dog bite two months prior was admitted to the hospital. Cerebral angiography, magnetic resonance angiography (MRA), and carotid color Doppler ultrasonography showed right CAD (aneurysm formation) with luminal stenosis (50%-69%), left common CAD (intramural hematoma formation). Bilateral common CAD caused by a dog bite is rare. The mechanism of CAD may be similar to iatrogenic dissection. After eliminating the contraindication of operation, right common carotid artery stenting was performed two months after conservative treatment.
Objective: To explore the potential category characteristics of sleep quality in conscious adult patients in the intensive care unit (ICU) and to analyze the differences in characteristics of ...different categories of conscious adult patients in the ICU. Methods: From 5/4/2023 to 30/6/2023, we selected ICU patients of a Class iii Grade A hospital in Wuhan as subjects by simple random sampling. The general information questionnaire, Acute Physiology and Chronic Health Evaluation II, Numerical Rating Scale (NRS)/Critical Care Pain Observation Tool (CPOT) and Richards-Campbell Sleep Questionnaire (RCSQ) were used for investigation. To analyze the latent profile of sleep quality characteristics of adult ICU awake patients and to identify the influencing factors of the latent profile through univariate analysis and logistic regression analysis. Results: A total of 298 awake ICU patients were investigated. There were three potential profiles of sleep quality characteristics, namely "low sleep quality" type (16.31%), "medium sleep quality" type (52.11%), and "high sleep quality" type (31.57%). Logistic regression analysis showed that age (36-60), disease type admitted to ICU, oxygen administration method, CPOT or NRS score, postoperative or not, use of analgesic drugs or not, and use of sleep-promoting drugs or not were the factors affecting the sleep quality of adult ICU awake patients (P < 0.05). Conclusion: The sleep quality of adult ICU awake patients has obvious classification characteristics. Health professionals can carry out individualized interventions according to the influencing factors of different potential profiles to improve the sleep quality of adult ICU awake patients. Keywords: ICU patients, sleep quality, sleep disorders, latent profile analysis, influencing factors
In order to find a more convenient processing method and more suitable paste formula for making VRLA batteries, hydrogen peroxide solution and red lead (Pb
3O
4) have been used together during the ...paste preparation. The use of hydrogen peroxide solution to replace the conventional sulphuric acid solution can accelerate the oxidation of free lead in the paste and therefore reduce the time for the plate curing, while the addition of red lead can enhance the cell formation and improve the cell performance. Based on these two beneficial functions, a new process for making VRLA cells was proposed and investigated. Cells were assembled directly from freshly pasted plates without undergoing the conventional plate curing and drying process, and the battery formation that followed was successful. The new processing resulted in an increase in the production efficiency and a substantial reduction in production time and cost. The battery performance, in terms of both the initial discharge capacity and the cycle life, is also improved by the use of red lead.
The aim of this study was to evaluate the
in vivo response following implantation into a rat model of three innovative hyaluronan derivatives for clinical use: HYAFF 7, HYAFF 11 and HYAFF 11p75 ...(respectively, the 100% ethyl ester, 100% and 75% benzyl esters). The tissue reaction evoked by films of these new biomaterials implanted into the dorsolumbar musculature of rats was assessed quantitatively using a well established technique based upon an image analysis system. The number of inflammatory cells present and the patterns of cell distribution around the implant up to a distance of 642 μm were examined at different time periods after implantation. Since a well-delineated tissue-material interface was needed for this type of investigation, it was not possible to apply image analysis to sections once dissolution of the implanted materials had begun. Films of both the total esters, HYAFF 7 and HYAFF 11, were found to undergo a slow dissolution process and, after a month, films of these materials were still present at the site of implantation. Differences in response to the two materials were observed only during the first two weeks, particularly with respect to neutrophil distribution and total cellularity. HYAFF 7 was found to be more reactive, with higher numbers of neutrophils near the surface of the implant than HYAFF 11. Thereafter, the differences between the two materials were minimal and owing mainly to a faster dissolution of HYAFF 7 films. After 3 and 5 months, considerable degradation of films of both total esters had occurred. Significant quantities of material appeared inside numerous macrophages with an ED1-positive phenotype. Only a very thin layer of fibrous connective tissue, indicative of low reactivity, was found to surround the site of implantation, separating the dissolved material and the phagocytic cells from healthy muscular tissue. ED2-positive macrophages were primarily confined within the lining connective tissue. The partial benzyl ester, HYAFF 11p75, showed a different behaviour. In fact, evidence of film dissolution was already present a week after the implantation. After two weeks, the implanted films were completely dissolved and numerous ED1-positive macrophages phagocytosing the material were observed at the site of implantation. Therefore, in agreement with previous
in vitro studies, which showed a greater susceptibility to degradation of hyaluronan derivatives with lower percentage of esterification, HYAFF 11p75 underwent resorption faster than the corresponding total ester.
An experimental investigation has been undertaken to study the behaviour of a single circular synthetic jet issued into turbulent boundary layer produced on a flat plate in cross flow. At the given ...free-stream conditions, the jet is also issued into laminar boundary layer so that an effective evaluation on the interaction of the vortices with the changing boundary layer could be made. The flow visualization technique is used in conjunction with the stereoscopic imaging system to reveal a unique quasi three-dimensional recognition of the vortices formed in either type of boundary layer under varying synthetic jet actuator (SJA) operating conditions. Firstly, the laminar boundary layer is produced on the flat plate with zero pressure gradient and later on the same boundary layer is triggered to turbulence using a trigger device. The free-stream conditions are justified by PIV measurements, in that the velocity profiles are drawn at given streamwise locations for both laminar and turbulent boundary layers. The parametric map is given to identify and bound the SJA operating parameters to produce the explicit vortical structures at the given conditions.
Graphical Abstract
Nasopharyngeal carcinoma (NPC), a highly invasive tumor, exhibits a distinctive racial and geographic distribution. As options of agents for effective combination chemoradiotherapy for advanced NPC ...are limited, novel therapeutic approaches are desperately needed. Here the potential of silencing NFBD1 in combination with PARP inhibition as a novel therapeutic strategy for NPC was investigated.
To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines via lentivirus mediated shRNA, and the colony formation, MTS assay, comet assay and apoptosis analysis were used to evaluate the sensitivity of NFBD1 knockdown on PARP inhibition. The signaling change was assessed by western blot, Immunofluorescence and flow cytometry. Furthermore, Xenografts model was used to evaluate the role of silencing NFBD1 in combination with PARP inhibition.
We find that silencing NFBD1 in combination with PARP inhibition significantly inhibits the cell proliferation and cell cycle checkpoint activity, and increases the apoptosis and DNA damage. Mechanistic studies reveal that NFBD1 loss blocks olaparib-induced homologous recombination repair by decreasing the formation of BRCA1, BRCA2 and RAD51 foci. Furthermore, the xenograft tumor model demonstrated significantly increases sensitivity towards PARP inhibition under NFBD1 deficiency.
We show that NFBD1 depletion may possess sensitizing effects of PARP inhibitor, and consequently offers novel therapeutic options for a significant subset of patients.
Prevalence studies of the recently identified TT virus (TTV) have suggested that parenteral transmission is a common route of infection, but other routes also appear likely. In this study, a high ...rate of cervical carriage (66%) of TTV DNA was found by polymerase chain reaction, which suggests that perinatal and sexual transmission is possible.
The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of prematurity. BPD occurs following ventilator treatment with supplemental oxygen for acute respiratory ...failure, and early inflammation. The hallmarks of the lung pathology are arrested lung development including fewer and larger alveoli with less septation, thickening of alveolar septa and impaired development of the capillary network. These changes may lead to life-long respiratory morbidity including asthma, reduced exercise capacity, early onset emphysema and pulmonary hypertension. Currently, there is no treatment for BPD. Mesenchymal stromal cells derived from the umbilical cord (UC-MSCs) improve lung structure and function in experimental BPD, and early phase clinical trials are underway. However, the optimal UC-MSC donor remains to be determined. The aim of this project is to compare healing effects of UC-MSC donors in hyperoxia-induced experimental BPD.
UC-MSCs derived from 5 human donors (1st term delivery TMSC, 2nd term delivery T2MSC, preterm delivery PMSC, preterm delivery with preeclampsia PPMSC, preterm delivery with chorioamnionitis PCMSC) were administered intratracheally at postnatal day (P) 4 in rat pups exposed to 85% oxygen from P0 to P14. At P21, survival, lung function (flexivent), lung structure (mean linear intercept), right ventricular hypertrophy (Fulton index), as well as lung vasculature at P35 (microCT) were assessed. Treatment with UC-MSCs increased survival in hyperoxia-exposed developing pups. In addition, TMSC, PMSC, PPMSC and PCMSC, but not T2MSC, improved lung compliance, lung growth and attenuated pulmonary hypertension when compared to control hyperoxic pups. Thus, donor source impacts beneficial effects of UC-MSCs in a rat BPD model. In the future, understanding the differences at the transcriptomic level between UC-MSC donors might improve the identification of the optimal MSC source for treatment of complications of extreme prematurity, the number one killer of infants below the age of 5.
We have employed a one-step (direct etching) metal-assisted chemical etching (MACE) technique to grow large-area Si nanostructures with smoother surface morphology and much less porous Si (PS) ...defects than those under the two-step (depositing and etching) MACE. A 17.63%-efficiency of the nano/ microstructures (N/M-Strus) based multicrystalline Si (mc-Si) solar cells has firstly surpassed that (17.45%) of traditional-micro-textured one with a standard solar wafer size of 156×156mm2. The key to success lies in the reduction of electrical loss by removing PS defects and employing shorter one-step-MACE-smoothened N/M-Strus, together with the optical gain from the combined antireflection of mc-Si N/M-Strus and SiNx:H thin films. The present work opens a way to the mass production of high efficient Si nanostructures based solar cells with a less-process-step and lower-cost approach.
•We prepare novel mc-Si nano/microstructures by employing a one-step MACE technique.•The trade-off of optical gain and electrical loss from nano/microstructures is achieved.•A 17.63%-efficiency has firstly surpassed that of traditional-micro-textured one.•The improving efficiency means a promising future for the mass production.
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