Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a.

We previously reported that the canonical innate immune receptor toll-like receptor 4 (TLR4) is critical in maintaining lung integrity. However, the molecular mechanisms via which TLR4 mediates its effect remained unclear. In the present study, we identified distinct contributions of lung endothelial cells (Ec) and epithelial cells TLR4 to pulmonary homeostasis using genetic-specific, lung- and cell-targeted in vivo methods. Emphysema was significantly prevented via the reconstituting of human TLR4 expression in the lung Ec of TLR4-/- mice. Lung Ec-silencing of TLR4 in wild-type mice induced emphysema, highlighting the specific and distinct role of Ec-expressed TLR4 in maintaining lung integrity. We also identified a previously unrecognized role of TLR4 in preventing expression of p16INK4a , a senescence-associated gene. Lung Ec-p16INK4a -silencing prevented TLR4-/- induced emphysema, revealing a new functional role for p16INK4a in lungs. TLR4 suppressed endogenous p16INK4a expression via HDAC2-mediated deacetylation of histone H4. These findings suggest a novel role for TLR4 in maintaining of lung homeostasis via epigenetic regulation of senescence-related gene expression

Perioperative stroke : a perspective on challenges and opportunities for experimental treatment and diagnostic strategies

Perioperative stroke is an ischemic or hemorrhagic cerebral event during or up to 30 days after surgery. It is a feared condition due to a relatively high incidence, difficulties in timely detection, and unfavorable outcome compared to spontaneously occurring stroke. Recent preclinical data suggest that specific pathophysiological mechanisms such as aggravated neuroinflammation contribute to the detrimental impact of perioperative stroke. Conventional treatment options are limited in the perioperative setting due to difficult diagnosis and medications affecting coagulation in may cases. On the contrary, the chance to anticipate cerebrovascular events at the time of surgery may pave the way for prevention strategies. This review provides an overview on perioperative stroke incidence, related problems, and underlying pathophysiological mechanisms. Based on this analysis, we assess experimental stroke treatments including neuroprotective approaches, cell therapies, and conditioning medicine strategies regarding their potential use in perioperative stroke. Interestingly, the specific aspects of perioperative stroke might enable a more effective application of experimental treatment strategies such as classical neuroprotection whereas others including cell therapies may be of limited use. We also discuss experimental diagnostic options for perioperative stroke augmenting classical clinical and imaging stroke diagnosis. While some experimental stroke treatments may have specific advantages in perioperative stroke, the paucity of established guidelines or multicenter clinical research initiatives currently limits their thorough investigation

Malignancy‐associated ischemic stroke : implications for diagnostic and therapeutic workup

Background: Patients with malignancies have an increased risk of suffering ischemic stroke via several mechanisms such as coagulation dysfunction and other malignancy-related effects as well as iatrogenic causes. Moreover, stroke can be the first sign of an occult malignancy, termed as malignancy-associated ischemic stroke (MAS). Therefore, timely diagnostic assessment and targeted management of this complex clinical situation are critical. Findings: Patients with both stroke and malignancy have atypical ages, risk factors, and often exhibit malignancy-related symptoms and multiple lesions on neuroimaging. New biomarkers such as eicosapentaenoic acid and blood mRNA profiles may help in distinguishing MAS from other strokes. In terms of treatment, malignancy should not be considered a contraindication, given comparable rates of recanalization and complications between stroke patients with or without malignancies. Conclusion: In this review, we summarize the latest developments in diagnosing and managing MAS, especially stroke with occult malignancies, and provide new recommendations from recently emerged clinical evidence for diagnostic and therapeutic workup strategies

The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation.

Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK-1, resulting in Th2 cell cytokine production. Circulating Dkk-1 was primarily from platelets, and the increase of Dkk-1 resulted in formation of leukocyte-platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-1 impaired Th2 cell cytokine production and leukocyte infiltration, protecting mice from house dust mite (HDM)-induced asthma or Leishmania major infection. These results highlight that Dkk-1 from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation

The Relationship among Emotional Leadership, Job Satisfaction and Organizational Commitment: Taking China’s Hotel Industry as an Example

This study investigated the impact of emotional leadership of leaders on organizational commitment of hotel employees, as well as the mediating role of job satisfaction. The results indicate that: (1) Emotional leadership and job satisfaction have positive effects on organizational commitment. (2) Emotional leadership has a positive effect on job satisfaction. (3) Job satisfaction plays a mediating role between emotional leadership and organizational commitment

Research on the Work Engagement of Hospitality Industry Staff from the Perspective of Tourism Management Informatization

With the development of information technology, the Internet and informatization have brought huge changes in tourism management. As the pillar industry of the tourism, the hospitality industry, are facing new requirements for transformation and optimization. How to retain talents and how to make talents willing to work are two important issues that hotels need to pay attention to in practice. Through a self-report questionnaire survey of 325 employees from hospitality industry, this paper use SPSS and AMOS tools to analyze the influencing factors of performance evaluation fairness (emloyee voice) and the employees’s work engagement, and constructs the impact mechanism model of them, meanwhile aim to give some helpful suggestions on indigenous research, and can probably enrich the informatization application in tourism management and innovation

Passive Daytime Radiative Cooling of Silica Aerogels

Silica aerogels are one of the most widely used aerogels, exhibiting excellent thermal insulation performance and ultralow density. However, owing to their plenitude of Si-O-Si bonds, they possess high infrared emissivity in the range of 8–13 µm and are potentially robust passive radiative cooling (PRC) materials. In this study, the PRC behavior of traditional silica aerogels prepared from methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) in outdoor environments was investigated. The silica aerogels possessed low thermal conductivity of 0.035 W/m·K and showed excellent thermal insulation performance in room environments. However, sub-ambient cooling of 12 °C was observed on a clear night and sub-ambient cooling of up to 7.5 °C was achieved in the daytime, which indicated that in these cases the silica aerogel became a robust cooling material rather than a thermal insulator owing to its high IR emissivity of 0.932 and high solar reflectance of 0.924. In summary, this study shows the PRC performance of silica aerogels, and the findings guide the utilization of silica aerogels by considering their application environments for achieving optimal thermal management behavior

Passive Daytime Radiative Cooling of Silica Aerogels

Silica aerogels are one of the most widely used aerogels, exhibiting excellent thermal insulation performance and ultralow density. However, owing to their plenitude of Si-O-Si bonds, they possess high infrared emissivity in the range of 8–13 µm and are potentially robust passive radiative cooling (PRC) materials. In this study, the PRC behavior of traditional silica aerogels prepared from methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) in outdoor environments was investigated. The silica aerogels possessed low thermal conductivity of 0.035 W/m·K and showed excellent thermal insulation performance in room environments. However, sub-ambient cooling of 12 °C was observed on a clear night and sub-ambient cooling of up to 7.5 °C was achieved in the daytime, which indicated that in these cases the silica aerogel became a robust cooling material rather than a thermal insulator owing to its high IR emissivity of 0.932 and high solar reflectance of 0.924. In summary, this study shows the PRC performance of silica aerogels, and the findings guide the utilization of silica aerogels by considering their application environments for achieving optimal thermal management behavior

The association between time-mean serum uric acid levels and the incidence of chronic kidney disease in the general population: a retrospective study

Abstract Background Investigations on the role of the time-mean serum uric acid (SUA) value in determining the risk of chronic kidney disease (CKD) are limited. We investigated whether the time-mean SUA value indicates the risk of CKD, and explored associations of the baseline and time-mean SUA levels with kidney function decline and incident CKD in a healthy population. Methods We initiated an inhabitant-based cohort study between January 2011 and December 2016. All participants completed a yearly medical check-up at the Zhejiang Province People’s Hospital and had baseline estimated glomerular filtration rates (eGFR) > 60 ml/min/1.73m2. The SUA level and eGFR were assessed every year in the follow-up period. A multivariate adjusted binary logistic regression analysis and Cox proportional hazards models were used to evaluate the risk of newly-developed CKD among different stratified groups. Results During the 6-year follow-up period, 227 (4.4%) participants developed CKD. In multivariable-adjusted analyses, the odds ratio (OR) for new-onset CKD increased, with higher time-mean SUA levels than at baseline (OR: 1.00 [reference], 2.709 [95% confidence interval: 1.836–5.293], 3.754 [1.898–7.428], and 7.462 [3.694–15.073]). After adjustment for potential cofounders, a multivariate Cox proportional hazard model showed that a higher SUA increased the risk of developing CKD (the adjusted hazard ratios of the highest and lowest quartiles for the baseline and time-mean SUA levels were 1.689 [1.058–2.696] and 6.320 [3.285–12.159], respectively). Conclusion An increased time-mean and single SUA value were independently associated with an increased likelihood of eGFR decline and development of new-onset CKD in the general population