In this study, we investigated lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6J mice by using behavioral tests, immunofluorescence, enzyme-linked immunosorbent ...assay (ELISA) and Western blot. We found that LPS treatment leads to sickness behavior and cognitive impairment in mice as shown in the Morris water maze and passive avoidance test, and these effects were accompanied by microglia activation (labeled by ionized calcium binding adaptor molecule-1, IBA-1) and neuronal cell loss (labeled by microtubule-associated protein 2, MAP-2) in the hippocampus. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the serum and brain homogenates were reduced by the LPS treatment, while the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE
) and nitric oxide (NO) were increased. In addition, LPS promoted the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the brain homogenates. The Western blot analysis showed that the nuclear factor kappa B (NF-κB) signaling pathway was activated in the LPS groups. Furthermore, VIPER, which is a TLR-4-specific inhibitory peptide, prevented the LPS-induced neuroinflammation and cognitive impairment. These data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, we compared the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections of LPS in LPS-induced neuroinflammation and cognitive impairment, and these data may provide additional insight for researchers performing neuroinflammation research.
Self‐powered and wearable electronics, which are away from the problems of batteries, can provide the sustainable and comfortable interactive service for people. In this work, cellular polypropylene ...piezoelectret, which is with excellent physical and electrical properties, is utilized to build the human body energy harvesting and self‐powered human health monitoring systems. The cellular polypropylene piezoelectret flexible generator can reach a maximum peak power density of ≈52.8 mW m−2. Simultaneously, self‐powered human body biological signals detecting sensors are demonstrated to detect the human physiological signals, such as coughing action and arterial pulses. This study strongly indicates the great compatibility and potential applications in human healthy monitoring may pave a new developing way for portable and wearable electronics systems.
Simple‐structured and efficient human body energy harvesting and self‐powered human health monitoring systems are demonstrated basing on the cellular polypropylene piezoelectret. A maximum peak power density of ≈52.8 mW m−2 is obtained and human physiological signals, such as coughing action and arterial pulse, are detected. These systems develop a new way for self‐powered and wearable electronics.
The roots of rock engineering disaster lie not only in cross-scale deterioration and failure of rock material, but also in large deformation and instability of rock discontinuities and structural ...bodies. The material-structure duality of rock mass influences the mechanical behavior of rock mass, resulting in continuous-discontinuous characteristics and singularity phenomena. Nevertheless, the cognition of the dominant transformation and cooperative effect between these complex mechanisms is still vague, and there is a lack of a numerical scheme considering both material and structral effects of rock. In this study, we constructed a unified numerical scheme (Rock failure and instability analysis, RFIA) that considers both material failure and structural instability of rock mass. By establishing the statistical meso-damage constitutive model, the damage and failure of rock materials were reflected, and by developing the finite deformation numerical formation considering current state response, the large deformation and instability of rock structural body were described. The proposed numerical scheme realized the synchronous simulation of both material failure induced instability, and structural instability induced failure of rock mass. The size effect on rock under uniaxial compression and the local collapse mechanism of the surrounding rock in deep slabbing tunnel were investigated by RFIA. Meanwhile, Rock failure analysis (RFA) that only considers rock material failure and Rock instability analysis (RIA) that only considers structural instability were performed in the simulations. The results show that there are dominant and competitive mechanisms between material failure and structural instability during failure and instability process of rock. For the rock structral body with dominant geometric features, its instability plays a decisive role in inducing catastrophe. The cooperative effect of material-structure is an important mechanism, which may result in large displacement and rotation of rock mass and the abrupt release of massive energy once instability induces the failure (e.g., in situation of rockburst).
•The decomposition of E. vaginatum litter is faster than that of Sphagnum.•Warming could promote decomposition of E. vaginatum and Sphagnum litter.•N addition promoted the decomposition of Sphagnum ...(low N) and vascular litter.•High N concentration inhibited the decomposition of Sphagnum litter.•Microorganisms regulated warming and N addition impacts on litter decomposition.
As one kind of the most important carbon (C) sink in the world, peatlands are sensitive to climate change. The decomposition of litter plays an important role in C fixation and nutrient utilization in peatlands. To reveal the mechanism of response of the litter decomposition to climate warming and the addition of nitrogen (N) in permafrostpeatlands, we selected two typical plants, Eriophorumvaginatum and Sphagnumpalustre, in the permafrost peatland of Da Xing’anling Mountains, China, as the research objects and conducted a 54-day litter decomposition experiment at 10 ℃ and 20 ℃. Three N addition treatments (CK: 0 mg N g−1, N1: 2.5 mg N g−1, and N2: 5 mg N g−1) were established. Our results showed that the E. vaginatum litter decomposed more quickly than that of Sphagnum, and an increase in temperature significantly promoted the litter decomposition and CO2 emission of E. vaginatum and Sphagnum. The addition of N promoted the decomposition of E. vaginatum litter, whereas the decomposition of Sphagnum litter was promoted by the N1 treatment but was inhibited by the N2 treatment. The enzyme activity in both types of litter was inhibited with the increase in temperature. The abundances of bacteria and fungi positively correlated with the decomposition constant and mean CO2 release rate by E. vaginatum and Sphagnum litter, indicating that the effects of temperature and N addition on the decomposition of plant litter were primarily regulated by microorganisms. This study provides a theoretical basis to understand and predict the effects of global climate change on the decomposition of plant litter in boreal peatlands.
Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in ...prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function.
RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships.
The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed.
A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.
Ischemic stroke can induce rapid disruption of blood-brain barrier (BBB). It has been suggested that increased BBB permeability can affect the pathological progression of ischemic tissue. However, ...the impact of increased BBB permeability on microglial activation and synaptic structures following reperfusion after ischemia remains unclear. In this study, we investigated microglial activation, dendritic damage and plasticity of dendritic spines after increasing BBB permeability following transient global cerebral ischemia in the somatosensory cortices in mice. Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischemia. Mannitol was used to increase the BBB permeability. Intravital two-photon imaging was performed to image the dendritic structures and BBB extravasation. Microglial morphology was quantitated using a skeletonization analysis method. To evaluate inflammation of cerebral cortex, the mRNA expression levels of integrin alpha M
, chemokine (C-X-C motif) ligand 10
and tumor necrosis factor alpha
were measured by fluorescent quantitative PCR. Intravital two-photon imaging revealed that mannitol caused a drastic increase in BBB extravasation during reperfusion after transient global ischemia. Increased BBB permeability induced by mannitol had no significant effect on inflammation and dendritic spines in healthy mice but triggered a marked de-ramification of microglia; importantly, in ischemic animals, mannitol accelerated de-ramification of microglia and aggravated inflammation at 3 h but not at 3 days following reperfusion after ischemia. Although mannitol did not cause significant change in the percentage of blebbed dendrites and did not affect the reversible recovery of the dendritic structures, excessive extravasation was accompanied with significant decrease in spine formation and increase in spine elimination during reperfusion in ischemic mice. These findings suggest that increased BBB permeability induced by mannitol can lead to acute activation of microglia and cause excessive loss of dendritic spines after transient global cerebral ischemia.
Alzheimer’s disease (AD), the most common dementia, is characterized by amyloid plaques (AP) and hyperphosphorylated tau tangles in the brain. Epidemiological evidence suggests that long-term chronic ...manganese (Mn) exposure increases the risk of AD. Additionally, the levels of Mn are elevated in the blood, cerebrospinal fluid and brain of AD patients, but the mechanisms underlying Mn enhancement of AD development remain unknown. Using the transgenic 3xTg-AD mouse model and mouse-derived microglia and neuroblastoma cell lines, we found that chronic 5-month Mn treatment increased Aβ burden in the cerebral cortex and hippocampus in these 3xTg-AD mice. Furthermore, we found that the β- and γ-secretase cleavage activities were markedly increased while α-secretase cleavage activity was reduced in the brain of Mn-treated AD mice, which might account for the increased Aβ accumulation. Equally important, acute Mn exposure did not alter -secretase 1 (BACE1) gene expression or amyloidosis in amyloidogenic mutant amyloid precursor protein gene hAPPsw-transfected N2a cells (APPsw-N2a); but in APPsw-N2a cells either co-cultured with microglia BV2 or cultured with microglia-conditioned media, Mn exposure increased BACE1 expression and amyloidosis. We further determined that Mn exposure promoted the activation of microglia both in 3xTg-AD mouse brains and in cultured BV2 microglia cells, and increased the secretion of the inflammatory cytokines interleukin-1 (IL-1β) and tumor necrosis factor- (TNF-α). Taken together, these results suggest that Mn may elevate the release of IL-1β and TNF-α from microglia that in turn stimulates the expression of BACE1 gene and protein and hence A production, providing a novel molecular mechanism for chronic Mn exposure to promote amyloidogenesis and AD pathogenesis.
Background:
Serum lactate is commonly measured in the perioperative period in patients who have undergone surgery for an acute type A aortic dissection (ATAAD). However, conflicting data has been ...reported as to whether lactate elevation is associated with short-term prognosis. The aim of the current study was to determine the association between perioperative arterial lactate levels and postoperative 30-day mortality.
Methods:
Patients who underwent repair of a ATAAD at our institution were retrospectively screened and those with comprehensive measurements of serum lactate before surgery and at 0, 1, 3, 6, 12, and 24 h after surgery in the intensive care unit (ICU) were selected for the analysis. Patients’ demographic features and outcomes were reviewed to determine risk factors associated with 30-day mortality using logistic regression modeling. The association between serum lactate levels at different time points and 30-day mortality were analyzed by receiver-operating characteristic curves.
Results:
513 patients were identified and retrospectively analyzed for this study including 66 patients (12.9%) who died within 30 days after surgery. Patients who died within 30 days after surgery had elevated lactate levels measured before surgery and at 0, 1, 3, 6, 12, and 24 h after their ICU stay. Lactate measured at 24 h post ICU admission (odds ratio, 2.131; 95% confidence interval, 1.346–3.374; p = 0.001) was a predictor of 30-day mortality. The area under the curve (AUC) for 30-day mortality with lactate levels at 12 h and 24 h post ICU stay were 0.820 and 0.805, respectively.
Conclusion:
Early elevation of lactate level is correlated with increased 30-day mortality in patients who received ATAAD surgical repair.
Background MAPK8IP2 is one of the JNK-interacting proteins (JIPs) family members, and is involved in the regulation of the JNK and P38 MAPK signaling pathways. MAPK8IP2 has been reported to be ...closely associated with several cancers. However, the biological function of MAPK8IP2 in prostate cancer (PCa) remains unclear. Methods MAPK8IP2 expression in PCa and subgroups of PCa was analyzed by public databases. The prognostic role of MAPK8IP2 in prostate cancer was analyzed using the Cox regression method. The potential mechanism by which MAPK8IP2 affects PCa progression was investigated by utilizing public data, including genetic alteration, DNA methylation, m6A methylation, and immune infiltration data. We further performed in vitro assays to validate the effect of MAPK8IP2 on PCa cell proliferation, migration and invasion. Results MAPK8IP2 is highly expressed in PCa tissues. Overexpression of MAPK8IP2 is associated with adverse clinicopathological factors and a poor prognosis in PCa. Receiver operating curve analysis showed that MAPK8IP2 can distinguish PCa tissues from non-PCa tissues with a certain accuracy (AUC = 0.814). The MAPK8IP2 genetic alteration rate was 2.6% and MAPK8IP2 alterations correlated with a poor prognosis. We also found that CDK12 and TP53 mutations were associated with MAPK8IP2 expression. The DNA methylation level of MAPK8IP2 was higher in primary tumors than in normal tissues, and the high MAPK8IP2 DNA methylation group of PCa patients had poor survival. Enrichment analysis indicated that MAPK8IP2 was involved in the MAPK signaling pathway. In vitro, knockdown of MAPK8IP2 inhibited PCa cell proliferation, migration and invasion. Conclusion MAPK8IP2 is a potential target for PCa treatment and can serve as a novel biomarker for PCa diagnosis and prognosis evaluation. Keywords: MAPK8IP2, Prostate cancer, Methylation, Prognosis, Tumor progression
The cellular piezoelectret generator (CPG) has drawn considerable attention as an emerging flexible energy harvester because of its advantages of a simple structure, easy assembly, a low cost, and ...eco‐friendliness. To facilitate practical applications, an initial theoretical study of CPGs is presented in this work, in which the output characteristics of CPGs can be optimized through an appropriate choice of parameters, including the electret dielectric permittivity, device structure, polarization process, and external load. A good agreement with experimental results is achieved, verifying the validity of the theoretical study. The reported theory offers a complete interpretation of the dynamic working mechanism of CPGs and provides significant guidance for the design of a CPG with enhanced yield.
A theoretical study of cellular piezoelectret generators (CPGs) is presented, focusing on the enhancement of their dynamic performance. An effective means to optimize the output characteristics of CPGs is found. This discovery will enhance performance and application range of future devices.
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