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Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life.
Rationale: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model. Methods: Pregnant rats were made diabetic on day 12 of gestation by streptozotocin (STZ). Experiments were conducted in 6 weeks old offspring. Results: There were significant increases in ischemia-induced cardiac infarction and gender-dependent left ventricular (LV) dysfunction in male offspring in GDM group as compared to controls. Exposure to GDM enhanced ROS level and caused a global DNA methylation in offspring cardiomyocytes. GDM attenuated cardiac Sirt 1 protein and p-Akt/Akt levels, but enhanced autophagy-related proteins expression (Atg 5 and LC3 II/LC3 I) as compared to controls. Ex-vivo treatment of DNA methylation inhibitor, 5-Aza directly inhibited Dnmt3A and enhanced Sirt 1 protein expression in fetal hearts. Furthermore, treatment with antioxidant, N-acetyl-cysteine (NAC) in offspring reversed GDM-mediated DNA hypermethylation, Sirt1 repression and autophagy-related gene protein overexpression in the hearts, and rescued GDM-induced deterioration in heart ischemic injury and LV dysfunction. Conclusion: Our data indicated that exposure to GDM induced offspring cardiac oxidative stress and DNA hypermethylation, resulting in an epigenetic down-regulation of Sirt1 gene and aberrant development of heart ischemia-sensitive phenotype, which suggests that Sirt 1-mediated signaling is the potential therapeutic target for the heart ischemic disease in offspring
Application of Acoustic Emission Technology in Monitoring Corrosion Induced Expansion Cracks of Reinforced Concrete
Acoustic emission (AE) technology is used to monitor the whole process of reinforced concrete rust expanding and cracking, and the accuracy of AE technology to distinguish the location and type of cracks in concrete rust expanding and cracking is studied and verified. The results show that the protective layer is accompanied by a large number of acoustic emission signals in the process of rust expansion and cracking, Moment tensor inversion can more accurately identify crack sources such as shear source, tensile source and mixed source; In the process of corrosion-induced expansion cracking, shear source cracks appear before tensile source cracks and mixed source cracks. It is feasible to use acoustic emission technology to locate and identify cracks
Motional decoherence in ultracold Rydberg atom quantum simulators of spin models
Ultracold Rydberg atom arrays are an emerging platform for quantum simulation
and computing. However, decoherence in these systems remains incompletely
understood. Recent experiments [Guardado-Sanchez et al. Phys. Rev. X 8, 021069
(2018)] observed strong decoherence in the quench and longitudinal-field-sweep
dynamics of two-dimensional Ising models realized with Lithium-6 Rydberg atoms
in optical lattices. This decoherence was conjectured to arise from spin-motion
coupling. Here we show that spin-motion coupling indeed leads to decoherence in
qualitative, and often quantitative, agreement with the experimental data,
treating the difficult spin-motion coupled problem using the discrete truncated
Wigner approximation method. We also show that this decoherence will be an
important factor to account for in future experiments with Rydberg atoms in
optical lattices and microtrap arrays, and discuss methods to mitigate the
effect of motion, such as using heavier atoms or deeper traps
Ligand-Hole in SnI6 Unit and Origin of Band Gap in Photovoltaic Perovskite Variant Cs2SnI6
This paper has been published in Bulletin of the Chemical Society of Japan,
which can be viewed at the following URL: http://doi.org/10.1246/bcsj.20150110
Cs2SnI6, a variant of perovskite CsSnI3, is expected for a photovoltaic
material. Based on a simple ionic model, it is expected that Cs2SnI6 is
composed of Cs+, I-, and Sn4+ ions and that the band gap is primarily made of
occupied I- 5p6 valence band maximum (VBM) and unoccupied Sn4+ 5s conduction
band minimum (CBM) similar to SnO2. In this work, we performed density
functional theory (DFT) calculations and revealed that the real oxidation state
of the Sn ion in Cs2SnI6 is +2 similar to CsSnI3. The +2 oxidation state of Sn
originates from 2 ligand holes in the [SnI6]2- octahedron unit, where the
ligand [I6] cluster has the apparent [I66-L+2]4- oxidation state, because the
band gap is formed mainly by occupied I 5p VBM and unoccupied I 5p CBM. The +2
oxidation state of Sn and the band gap are originated from the intracluster
hybridization and stabilized by the strong covalent interaction between Sn and
I
A survey-based analysis of the public's willingness for disaster relief in China
Meteorological disasters frequently occur in China and around the world. These natural hazards can cause huge economic losses and threaten the personal safety of citizens. The public’s willingness to engage with disaster relief efforts and the degree of participation is critical to reduce the impact of such disasters. This study conducted a survey with 62,903 respondents from China. The study utilized statistical analysis and correlation analysis in order to understand the differences and similarities of the public’s willingness to take part in disaster relief across gender and age. The study found that: (1) the public’s awareness of insurance and willingness to make donations during climate disasters is low, and that more than half of the public are only willing to insure for very less money; (2) although the public has very high enthusiasm to participate in disaster relief, they are less willing to learn the basic skills of reducing disasters and for participating in training for disaster reduction as volunteers. This was especially the case for elderly citizens and females; (3) the willingness of the public to prevent and reduce disasters is high, and this was the case across various gender and age groups. Finally, the study puts forward several measures to improve the uptake of disaster relief and disaster prevention among citizens
Reinfection of Nine-Valent Human Papillomavirus Vaccine Types Among HIV-Negative Men Who Have Sex With Men: A Prospective Cohort Study
Objectives: Reinfection of human papillomavirus (HPV) among men who have sex with men (MSM) after clearing the infection of HPV has not been well characterized. To understand the reinfection of HPV among human immunodeficiency virus (HIV) negative MSM without HPV vaccine, we analyzed the reinfection of nine-valent HPV vaccine (9v-HPV) types.
Methods: Data were acquired from a prospective cohort study among HIV-negative MSM in Urumqi of Xinjiang from 1 April 2016 to 14 July 2020. Participants were recruited through a local non-government organization using a website advertisement. Self-administered questionnaires and self-collected anal swabs were collected at baseline and every 6 months. The incidence rates of reinfection was calculated based on the number of events divided by person-months of observation of event risk. 95% confidence intervals (CIs) were calculated based on the Poisson distribution.
Results: A total of 515 HIV-negative unvaccinated MSM were included with a mean age of 30.93 years (SD 7.85), and 27.68% were reinfected with any 9v-HPV type after clearance. The reinfection incidence rate of any 9v-HPV was 14.47 per 1000 person-months (95% CI: 11.52–17.87). HPV52 was the most common type of reinfection, with a reinfection rate of 17.96 per 1,000 person months (95% CI: 11.58–26.33). Univariate analysis showed that MSM over the age of 30 had a slightly higher risk of reinfection with any 9v-HPV (Hazard ratio (HR): 1.57; 95% CI: 1.01–2.45), but no significant association was observed in multivariate analysis.
Conclusions: Our study showed MSM without HPV vaccine will become reinfected following the natural clearance of specific HPV types. It is also suggested that HPV vaccination is recommended not only prior to sexual debut but also after viral clearance for MSM to reduce HPV prevalence
Single-cell RNA sequencing reveals distinct chondrocyte states in femoral cartilage under weight-bearing load in Rheumatoid arthritis
IntroductionRheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear.MethodsIn this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type. ResultsA total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages.ConclusionTwo new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis
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