Malfunction of astrocyte and cholinergic input is involved in postoperative impairment of hippocampal synaptic plasticity and cognitive function.

Postoperative delirium (POD) occurs in a few days after major surgery under general anesthesia and may cause serious health problems. However, effective intervention and treatment remain unavailable because the underlying mechanisms have far been elucidated. In the present study, we explored the role of the malfunctioned astrocytes in POD. Our results showed that mice with tibia fracture displayed spatial and temporal memory impairments, reduced LTP, and activated astrocytes in the hippocampus in early postoperative stage. Using electrophysiological and Ca2+ imaging techniques in hippocampal slices, we demonstrated the malfunctions of astrocytes in surgery mice: depolarized resting membrane potential, higher membrane conductance and capacitance, and attenuated Ca2+ elevation in response to external stimulation. The degraded calcium signaling in hippocampal astrocytes in surgery mice was restored by correcting the diminution of acetylcholine release with galantamine. Furthermore, pharmacologically blocking astrocyte activation with fluorocitrate and enhancing cholinergic inputs with galantamine normalized hippocampal LTP in surgery mice. Finally, inhibition of astrocyte activation with fluorocitrate in the hippocampus improved cognitive function in surgery mice. Therefore, the prevention of astrocyte activation may be a valuable strategy for the intervention of cognitive dysfunction in POD, and acetylcholine receptors may be valid drug targets for this purpose.

ETS proto-oncogene 1 modulates PTP1B expression to participate in high glucose-mediated endothelial inflammation.

Hyperglycemia-induced endothelial inflammation participates in the pathogenesis of cardiovascular complications in diabetics. Previous studies showed that protein tyrosine phosphatase 1B (PTP1B) and ETS proto-oncogene 1 (ets1) are involved in hyperglycemia-induced endothelial inflammation. In this study, we hypothesized that ets1 modulates PTP1B expression, thus playing a crucial role in hyperglycemia-induced vascular endothelial inflammation. Our results indicated that high glucose increases monocyte/endothelial adhesion, vascular cell adhesion molecule-1 (VCAM-1) expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose-mediated endothelial inflammation is reversed by PTP1B silencing. In addition, high glucose increases ets1 expression in HUVECs. silencing reverses high glucose-mediated endothelial inflammation. Furthermore, the effect of ets1 overexpression is similar to that of high glucose treatment, which is counteracted by si-PTP1B. The results from ChIP assays indicated that ets1 occupies the PTP1B promoter region. Ets1 overexpression enhances PTP1B promoter activity, which is disappeared after specific binding site mutation. experiments demonstrated that the expressions of VCAM-1, PTP1B, and ets1, as well as the phosphorylation of p65 are augmented in the aorta of diabetic rats. In conclusion, ets1 contributes to hyperglycemia-mediated endothelial inflammation via upregulation of PTP1B expression.

Applications of UAS in Crop Biomass Monitoring: A Review.

Biomass is an important indicator for evaluating crops. The rapid, accurate and nondestructive monitoring of biomass is the key to smart agriculture and precision agriculture. Traditional detection methods are based on destructive measurements. Although satellite remote sensing, manned airborne equipment, and vehicle-mounted equipment can nondestructively collect measurements, they are limited by low accuracy, poor flexibility, and high cost. As nondestructive remote sensing equipment with high precision, high flexibility, and low-cost, unmanned aerial systems (UAS) have been widely used to monitor crop biomass. In this review, UAS platforms and sensors, biomass indices, and data analysis methods are presented. The improvements of UAS in monitoring crop biomass in recent years are introduced, and multisensor fusion, multi-index fusion, the consideration of features not directly related to monitoring biomass, the adoption of advanced algorithms and the use of low-cost sensors are reviewed to highlight the potential for monitoring crop biomass with UAS. Considering the progress made to solve this type of problem, we also suggest some directions for future research. Furthermore, it is expected that the challenge of UAS promotion will be overcome in the future, which is conducive to the realization of smart agriculture and precision agriculture.

Glycogen phosphorylase B promotes cell proliferation and migration through PI3K/AKT pathway in non-small cell lung cancer.

OBJECTIVE: Glycogen phosphorylase B (PYGB), the rate-determining enzyme in glycogen degradation, plays a critical role in progression of various tumors. The present study focused on the potential molecular mechanism toward PYGB in non-small cell lung cancer (NSCLC) progression. METHODS: Expression of PYGB in NSCLC tissues and cell lines was evaluated via quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. Cell viability, proliferation and apoptosis were investigated using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-bromo-2-deoxyuridine (BrdU) and flow cytometry, respectively. Cell migration and invasion ability were detected by wound healing and transwell invasion assays, respectively. The in vivo effect of PYGB on NSCLC tumor growth was determined via subcutaneous xenotransplanted tumor model. RESULTS: PYGB was upregulated in NSCLC tissues and cell lines, suggesting a poor prognosis in NSCLC patients. In vitro functional assays indicated that knockdown of PYGB suppressed cell viability, proliferation, migration and invasion, while promoted cell apoptosis in NSCLC. Mechanistically, we found that overexpression of PYGB could activate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, while these effects were effectively reversed by knockdown of PYGB. In vivo tumorigenesis and PI3K/AKT signaling pathway were also inhibited by PYGB knockdown. CONCLUSIONS: Knockdown of PYGB suppressed NSCLC progression, suggesting PYGB as a novel biomarker and potential molecular therapeutic target for further investigation in NSCLC.

Ketamine attenuates high-glucose-mediated endothelial inflammation in human umbilical vein endothelial cells.

Hyperglycemia mediates oxidative stress, thus inducing transcription factor nuclear factor kappa B (NF-κB) activation, increasing endothelial adhesion molecule expression and monocyte/endothelial interaction, and resulting in endothelial injury. Ketamine was reported to attenuate oxidative stress in many cases. In this research, we determined whether and how ketamine protects against high-glucose-mediated augmentation of monocyte/endothelial interaction and endothelial adhesion molecule expression in human umbilical vein endothelial cells. High glucose augmented monocyte/endothelial adhesion and endothelial adhesion molecule expression. High glucose induced reactive oxygen species (ROS) production and augmented phospho-protein kinase C (p-PKC) ßII expression and PKC activity. Moreover, high glucose inhibited the inhibitory subunit of nuclear factor-κBα (IκBα) expression in the cytoplasm and induced NF-κB nuclear translocation. Importantly, the effects induced by high glucose were counteracted by ketamine treatment. Further, CGP53353, a PKC ßII inhibitor, inhibited high-glucose-mediated NF-κB nuclear translocation, attenuated adhesion molecule expression, and reduced monocyte/endothelial interaction. Further, these effects of ketamine against high-glucose-induced endothelial injury were inhibited by phorbol 12-myristate 13-acetate, a PKC ßII activator. In conclusion, ketamine, via reducing ROS accumulation, inhibited PKC ßII Ser660 phosphorylation and PKC and NF-κB activation and reduced high-glucose-induced expression of endothelial adhesion molecules and monocyte/endothelial interaction.

Dexmedetomidine attenuates LPS-mediated BV2 microglia cells inflammation via inhibition of glycolysis.

Microglia inflammation induces pro-inflammatory cytokines and pro-inflammatory enzymes expression, thus leading to inflammation-mediated neuronal cell death. Increased intracellular glycolysis participates in LPS-mediated microglia inflammation. Dexmedetomidine exhibits neuroprotective effects in some situations. In this study, we mainly focused on whether and how dexmedetomidine inhibits LPS-mediated cellular glycolysis and inflammation in BV2 cells. LPS induced pro-inflammatory cytokines and pro-inflammatory enzymes expression, and increased glycolysis capacity in BV2 cells. Moreover, inhibition of glycolysis by 2DG attenuated LPS-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression. Moreover, LPS upregulated hypoxia-inducible factor 1α (HIF1α) expression and decreased sirt1 expression. Dexmedetomidine counteracted these effects induced by LPS. Further, 2-methoxyestradiol, a HIF1α inhibitor, could inhibit LPS-mediated glycolysis and inflammation in BV2 cells, which was similar to the effects of dexmedetomidine. In addition, these effects of dexmedetomidine could be reversed by EX527, a sirt1 inhibitor. The present study indicated that dexmedetomidine, via upregulation of sirt1 expression, inhibited HIF-1α expression and glycolysis, thus reducing LPS-mediated inflammation in BV2 cells.

An oral second-generation proteasome inhibitor oprozomib significantly inhibits lung cancer in a p53 independent manner in vitro.

The destruction of proteins via the ubiquitin-proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious to cell survival and are promising anticancer agents. Oprozomib (OPZ), an oral second-generation proteasome inhibitor, has been shown to inhibit the growth of several cancers in preclinical and clinical trials, including multiple myeloma and head and neck cancers, but its effects on lung cancer has not yet been determined. In this study, we evaluated the inhibitory effects of OPZ on lung cancer cell lines in vitro. The results showed that OPZ significantly suppressed cell proliferation and strongly induced apoptosis in both tested lung cancer cells independent of p53 expression. OPZ was able to cause obvious caspase 3 and PARP cleavages and stabilize p53 and its transcriptional targets p21, PUMA, and Noxa. Moreover, OPZ was capable of sensitizing lung cancer cells to the conventional chemotherapeutic drug cisplatin. Our study provides preclinical data and sheds light on the potential applications of proteasome inhibitor OPZ in lung cancer treatment.

Galantamine reversed early postoperative cognitive deficit via alleviating inflammation and enhancing synaptic transmission in mouse hippocampus.

Postoperative cognitive dysfunction (POCD) is commonly seen in patients undergoing major surgeries and may persist. Although neuroinflammation is one of the important contributors to the development of POCD, the mechanisms underlying POCD remain unclear. We performed stabilized tibial fracture operation in male mice. In comparison with sham mice (anesthesia only), the surgery mice exhibited cognitive deficits in a fear conditioning paradigm at postsurgery day 3-7, and increased numbers of microglia and elevated levels of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) without change of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Electrophysiological recordings from CA1 hippocampal neurons revealed that POCD mice exhibited impairment in AMPA receptor-mediated evoked excitatory postsynaptic currents (eEPSCs) without alteration in the rectification property of AMPA receptors. Interestingly, daily intraperitoneal administration of galantamine, an inhibitor of acetylcholinesterase, reversed cognitive dysfunction in surgery mice and attenuated accumulation of microglia and protein levels of IL-1ß, IL-6 and TNF-α in the hippocampus. Additionally, galantamine potentiated AMPA receptor-mediated eEPSCs in the hippocampus more prominent in surgery mice than in sham mice. Therefore, enhancement of cholinergic tone in the hippocampus might be a therapeutic strategy for early POCD in terms of suppression of inflammation and normalization of excitatory synaptic transmission.