Activation of an AMP-activated protein kinase is involved in post-diapause development of Artemia franciscana encysted embryos

<p>Abstract</p> <p>Background</p> <p>Cysts of <it>Artemia </it>can remain in a dormant state for long periods with a very low metabolic rate, and only resume their development with the approach of favorable conditions. The post-diapause development is a very complicated process involving a variety of metabolic and biochemical events. However, the intrinsic mechanisms that regulate this process are unclear.</p> <p>Results</p> <p>Herein we report the specific activation of an AMP-activated protein kinase (AMPK) in the post-diapause developmental process of <it>Artemia</it>. Using a phospho-AMPKα antibody, AMPK was shown to be phosphorylated in the post-diapause developmental process. Results of kinase assay analysis showed that this phosphorylation is essential for AMPK activation. Using whole-mount immunohistochemistry, phosphorylated AMPK was shown to be predominantly located in the ectoderm of the early developed embryos in a ring shape; however, the location and shape of the activation region changed as development proceeded. Additionally, Western blotting analysis on different portions of the cyst extracts showed that phosphorylated AMPKα localized to the nuclei and this location was not affected by intracellular pH. Confocal microscopy analysis of immunofluorescent stained cyst nuclei further showed that AMPKα localized to the nuclei when activated. Moreover, cellular AMP, ADP, and ATP levels in developing cysts were determined by HPLC, and the results showed that the activation of <it>Artemia </it>AMPK may not be associated with cellular AMP:ATP ratios, suggesting other pathways for regulation of <it>Artemia </it>AMPK activity.</p> <p>Conclusion</p> <p>Together, we report evidence demonstrating the activation of AMPK in <it>Artemia </it>developing cysts and present an argument for its role in the development-related gene expression and energy control in certain cells during post-diapause development of <it>Artemia</it>.</p

Analytical Modeling of a Doubly Clamped Flexible Piezoelectric Energy Harvester with Axial Excitation and Its Experimental Characterization

With the rapid development of wearable electronics, novel power solutions are required to adapt to flexible surfaces for widespread applications, thus flexible energy harvesters have been extensively studied for their flexibility and stretchability. However, poor power output and insufficient sensitivity to environmental changes limit its widespread application in engineering practice. A doubly clamped flexible piezoelectric energy harvester (FPEH) with axial excitation is therefore proposed for higher power output in a low-frequency vibration environment. Combining the Euler–Bernoulli beam theory and the D’Alembert principle, the differential dynamic equation of the doubly clamped energy harvester is derived, in which the excitation mode of axial load with pre-deformation is considered. A numerical solution of voltage amplitude and average power is obtained using the Rayleigh–Ritz method. Output power of 22.5 μW at 27.1 Hz, with the optimal load resistance being 1 MΩ, is determined by the frequency sweeping analysis. In order to power electronic devices, the converted alternating electric energy should be rectified into direct current energy. By connecting to the MDA2500 standard rectified electric bridge, a rectified DC output voltage across the 1 MΩ load resistor is characterized to be 2.39 V. For further validation of the mechanical-electrical dynamical model of the doubly clamped flexible piezoelectric energy harvester, its output performances, including both its frequency response and resistance load matching performances, are experimentally characterized. From the experimental results, the maximum output power is 1.38 μW, with a load resistance of 5.7 MΩ at 27 Hz, and the rectified DC output voltage reaches 1.84 V, which shows coincidence with simulation results and is proved to be sufficient for powering LED electronics

A novel 7-chemokine-genes predictive signature for prognosis and therapeutic response in renal clear cell carcinoma

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort.Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package “Seurat” was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the “ssGSEA” algorithm. In order to develop possible medications for patients with high-risk ccRCC, the “pRRophetic” package is employed.Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature’s biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications.Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient’s prognosis for ccRCC and reflect the disease’s complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

High Diversity of Tick-associated Microbiota from Five Tick Species in Yunnan, China

Ticks are obligate blood-sucking vectors for multiple zoonotic diseases. In this study, tick samples were collected from Yunnan Province, China, which is well-known as the “Global Biodiversity Hotspot” in the world. This study aimed to clarify the microbial populations, including pathogens, associated with ticks and to identify the diversity of tick-borne microbiota in this region. The 16S rRNA full-length sequencing from pooled tick DNA samples and PCR amplification of pathogenic genera from individual samples were performed to understand tick-associated microbiota in this region. A total of 191 adult ticks of 5 tick species were included and revealed 11 phyla and 126 genera bacteria, including pathogenic Anaplasma , Ehrlichia , Candidatus Neoehrlichia, Rickettsia , Borrelia , and Babesia . Further identification suggested that Rickettsia sp. YN01 was a variant strain of Rickettsia spp. IG-1, but Rickettsia sp. YN02 and Rickettsia sp. YN03, were potentially two new SFGR species. This study revealed the complexity of ecological interactions between host and microbe and provided insight for the biological control of ticks. A high microbial diversity in ticks from Yunnan was identified, and more investigation should be undertaken to elucidate the pathogenicity in the area

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4+ T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4+ T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4+ T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr394). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4+ T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr394) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4+ T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases