BACKGROUNDIdeal acellular dermal matrices (ADM) for breast reconstruction exhibit native extracellular matrix (ECM) structure to allow rapid biointegration and appropriate mechanical properties for ...desired clinical outcomes. In a novel in vivo model of irradiated breast reconstruction, we describe the cellular and vascular ingrowth of Artia, a porcine product chemically prepared to mimic the biomechanics of human ADM, with retained natural ECM structure to encourage cellular ingrowth.
METHODSUtilizing the murine dorsal skinfold model, Artia was implanted into 16 C57bl/6 mice. Eight of the mice received a single dose 35 Gy radiation to the skin, followed by 12 weeks to produce radiation fibrosis and 8 mice served as nonradiated controls. Real-time photoacoustic microscopy of vascular integration and oxygen saturation within the ADM were made over 14 days. At 21 days, vascular ingrowth (CD31), fibroblast scar tissue formation (alpha smooth-muscle actin α-SMA, vimentin), and macrophage function (M2/M1 ratio) were evaluated. Scanning electron microscopy images of Artia were produced to help interpret the potential orientation of cellular and vascular ingrowth.
RESULTSRepeated photoacoustic microscopy imaging demonstrated vascular ingrowth increasing over 14 days, with a commensurate increase in oxygen saturation within both radiated and nonradiated ADM—albeit at an insignificantly lower rate in the radiated group. By day 21, robust CD31 staining was seen that was insignificantly greater in the nonradiated group. Of the fibroblast markers, vimentin expression was significantly greater in the radiated group (P < 0.05). Macrophage lineage phenotype was consistent with remodeling physiology in both radiated and nonradiated groups. Scanning electron microscopy demonstrated transversely organized collagen fibrils with natural porous ECM structure to allow cellular ingrowth.
CONCLUSIONSArtia demonstrates appropriate biointegration, with increased oxygen saturation by 14 days, consistent with the performance of other collagen substrates in this model. Radiation fibrosis resulted in higher vimentin expression yet did not impact macrophage phenotype while only modestly decreasing Artia biointegration suggesting that ADM may have a role in reconstructive efforts in a radiated setting. Taken together with its enhanced biomechanics, this porcine ADM product is well poised to be clinically applicable to breast reconstruction.
We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus ...OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032 + 4127 and the other mainly with a pulsar wind nebula PWN G75.2 + 0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.
We investigated the possible correlations between N-acetyltransferase-2 (NAT2) gene polymorphisms and the risk of coronary heart disease (CHD). CHD patients (113) and healthy controls (118) were ...enrolled from the First People's Hospital of Yuhang between January 2013 and June 2014. The patients were divided into mild CHD (N = 72) and severe CHD (N = 41) subgroups. DNA samples were extracted and the distributions of NAT2 polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristic indexes of severe CHD patients were also examined for relevant statistical analysis. WT, M1, M2, and M3 alleles were observed in both case and control groups. PCR-RFLP identified a wild-type homozygote, WT/WT; a mutant heterozygote, WT/Mx; and a mutant homozygote, Mx/Mx (x = 1, 2, and 3) variant of the NAT2 genotype. Mx/Mx differed significantly between case and control groups (P < 0.05); the frequencies of all four alleles did not differ significantly between case and control groups (P > 0.05). Slow acetylator genotype frequencies were notably higher in the case group than in the control group (P < 0.05). Individuals with the slow acetylator genotype were at 1.97-times higher risk of CHD and also displayed higher triglyceride and lower high-density lipoprotein cholesterol levels than those with the rapid acetylator genotype (P < 0.05). Therefore, the NAT2 polymorphism was believed to be associated with increased risk of CHD, with the NAT2 slow acetylator genotype serving as a risk factor for severe CHD in a Chinese population.
Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit ...mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors.
Biogenic silver nanoparticles (AgNPs) have wider range of biomedical applications. The present work synthesized Tp-AgNPs using mycelial extract of endophytic fungus
(MEEF), characterized, and ...analyzed for antibacterial, anti-proliferation and cell wounding healing activities.
The synthesized Tp-AgNPs were characterized by UV-visible spectrophotometer (UV-Vis), field emission transmission electron microscopy (FETEM) with energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), particle size analysis (PSA) and X-ray diffraction (XRD). Further, antibacterial activity was determined by Kirby-Bauer test and anti-proliferation activity was tested in human lung carcinoma A549 by water-soluble tetrazolium and flow cytometer assay. In addition, cell wounding healing activity was determined by scratch assay.
UV-Vis results displayed a strong absorption peak from 390 nm to 420 nm, which indicated the successful synthesis of Tp-AgNPs. FETEM-EDS results indicated the round and triangle shaped Tp-AgNPs with the average size of 25 nm in accordance with PSA. FTIR analysis indicated the involvement of various functional molecules from MEEF in the synthesis of Tp-AgNPs. XRD result proved nature of Tp-AgNPs as a high-quality crystal. The Tp-AgNPs significantly inhibited the growth of bacterial pathogens at the minimal inhibitory concentration of 16.12 μg.mL
for Gram
, and 13.98 μg.mL
for Gram
bacteria. Further, Tp-AgNPs (2 μg.mL
) showed a strong anti-proliferation effect in A549. Interestingly, Tp-AgNPs was not cytotoxic to normal NIH3T3 cells. In addition, the NPs exhibited a strong cell wounding healing activity.
This work biosynthesized AgNPs with strong antibacterial, anticancer and cell wound healing properties using endophytic fungus
.
The carotid siphon is a natural barrier to intracranial interventions. Our aim was to make a model of the human intracranial internal carotid artery (ICA) and to test the navigability of covered ...stents for intracranial applications.
A digital tube was made on the basis of raw MR images of the human ICA. It was transferred into 10 physical models and then coated with silicone by using a 3D rapid prototyping (RP) machine. Ten dogs then underwent surgery. Their common carotid arteries (CCAs) were exposed, cut, and passed through 1 of the tubes. Finally, the vascular models were made by reanastomosis of their CCAs. Eight expended polytetrafluoroethylene (e-PTFE) covered stents (two 3.5 x 16 mm, two 3.5 x 13 mm, two 3.5 x 10 mm, and two 3.5 x 7 mm) were implanted 1 week later. Two dogs remained as controls. The performance of the device was evaluated by angiography and histopathologic examination.
Ten animal models were successfully constructed. There was no vascular spasm or thrombosis when assessed by angiography. Destruction of the tunica intima and media was found in the 3.5 x 16 mm stent group. Destruction of the endothelium was found in the 3.5 x 13 mm stent group, and only flattening of the endothelium was found in the 3.5 x 10 mm and 3.5 x 7 mm stent groups.
The experimental model was thought to simulate adequately the geometry of the human ICA and, thus, would be an effective tool for the research and testing of neurovascular devices. The length of the stent is 1 factor influencing the navigability in tortuous vessels.
BackgroundTuberculosis (TB) remains a significant global health emergency caused by Mycobacterium tuberculosis (Mtb). The epidemiology, transmission, genotypes, mutational patterns, and clinical ...consequences of TB have been extensively studied worldwide, however, there is a lack of information regarding the epidemiology and mutational patterns of Mtb in Pakistan, specifically concerning the prevalence of multi-drug resistant TB (MDR-TB).MethodsThis study aimed to investigate the incidence of Mtb and associated mutational patterns using the line probe assay (LPA). Previous studies have reported a high frequency of mutations in the rpoB, inhA, and katG genes, which are associated with resistance to rifampicin (RIF) and isoniazid (INH). Therefore, the current study utilized LPA to detect mutations in the rpoB, katG, and inhA genes to identify multi-drug resistant Mtb.ResultsLPA analysis of a large pool of Mtb isolates, including samples from 241 sputum-positive patients, revealed that 34.85% of isolates were identified as MDR-TB, consistent with reports from various regions worldwide. The most prevalent mutations observed were rpoB S531L and inhA promoter C15T, which were associated with resistance to RIF and INH, respectively.ConclusionsThis study highlights the effectiveness of GenoType MTBDRplus and MTBDRsl assays as valuable tools for TB management. These assays enable rapid detection of resistance to RIF, INH, and fluoroquinolones (FQs) in Mtb clinical isolates, surpassing the limitations of solid and liquid media-based methods. The findings contribute to our understanding of MDR-TB epidemiology and provide insights into the genetic profiles of Mtb in Pakistan, which are essential for effective TB control strategies.
Small ubiquitin-like modifier (SUMO) modification is emerging as an important control in transcription regulation. Here, we show that CREB-binding protein (CBP), a versatile transcriptional ...coactivator for numerous transcription factors in response to diverse signaling events, can be modified by SUMO-1 at lysine residues 999, 1034, and 1057 both in vitro and in vivo. Mutation of the SUMO acceptor lysine residues either individually or in combination enhanced CBP transcriptional activity, and expression of a SUMO protease SENP2 potentiated the transcriptional activity of CBP wild-type but not its sumoylation mutant, indicating that SUMO modification negatively regulates CBP transcriptional activity. Furthermore, we demonstrated an interaction of SUMO-1-modified CBP with the transcriptional corepressor Daxx and an essential role of Daxx in mediating SUMO-dependent transcriptional regulation of CBP through histone deacetylase 2 recruitment. Together, our findings indicate that SUMO modification and subsequent recruitment of Daxx represent a previously undescribed mechanism in modulating CBP transcriptional potential.
Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from ...astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.
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