The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts.

This study aimed to investigate the effect of aquaporin-4 (AQP4) on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts. A model of diffuse ischemic brain injury was established, and adenovirus was injected stereotactically through the lateral ventricle of mice. The water content of the brain tissue was measured. The co-expression of glial fibrillary acidic protein (GFAP) and AQP4 and the aggregation of p-tau and neuronal marker were detected through immunofluorescence double staining. The expression of phosphorylated microtubule-associated protein tau (p-tau, Ser202/Thr205, Thr205, Ser396, Ser404), interleukin(IL)-6, IL-1ß, tumor necrosis factor (TNF)-a, growth associated protein43 (GAP43), GFAP, and ionized calcium-binding adapter molecule 1 (Iba1) was detected through Western blot. It was found that the brain water content in the model group was increased and decreased after the AQP4 interference. Compared with the sham group, the expression of GFAP, p-tau, IL-1ß, TNF-a, Iba1, and p-tau was increased in the model group (p < 0.05). Compared with the model group, the expression of p-tau, IL-6, IL-1ß, TNF-a, GFAP, and Iba1 was decreased after AQP4 interference (p < 0.05). It is indicated that AQP4 positively regulates neurodegeneration and persistent neuroinflammation caused by tau protein aggregation after cerebral microinfarcts.

Object-Process Methodology as an Alternative to Human Factors Task Analysis.

OBJECTIVE: We define and demonstrate the use of OPM-TA-a model-based task analysis (TA) framework that uses object-process methodology (OPM) ISO 19450 as a viable alternative to traditional TA techniques. BACKGROUND: A variety of different TA methods exist in human factors engineering, and several of them are often applied successively for a broad task representation, making it difficult to follow. METHOD: Using OPM-TA, we modeled how an International Space Station (ISS) astronaut would support extravehicular activities using the existing robotic arm workstation with a new control panel and an electronic procedure system. The modeling employed traditional TA methods and the new OPM-TA approach, enabling a comparison between them. RESULTS: While the initial stages of modeling with OPM-TA follow those of traditional TA, OPM-TA modeling yields an executable and logically verifiable model of the entire human-robot system. Both OPM's hierarchical set of diagrams and the equivalent, automatically generated statements in a subset of natural language text specify how objects and processes relate to each other at increasingly detailed levels. The graphic and textual OPM modalities specify the system's architecture, which enables its function and benefits its users. To verify the model logical correctness model, we executed it using OPM's simulation capability. CONCLUSION: OPM-TA was able to unify traditional TA methods and expand their capabilities. The formal yet intuitive OPM-TA approach fuses and extends traditional TA methods, which are not amenable to simulation. It therefore can potentially become a widely used means for TA and human-machine procedure development and testing.

Change in the pituitary stalk deviation angle after transsphenoidal surgery can predict the development of diabetes insipidus for pituitary adenomas.

Purpose: We aimed to assess the factors influencing the development of diabetes insipidus after transsphenoidal surgery for pituitary adenomas. Methods: A retrospective analysis was conducted on the clinical data of patients with pituitary adenomas who underwent transsphenoidal surgery. The predictors of postoperative diabetes insipidus were determined using statistical analysis. Results: Of the 415 patients who underwent microscopic transsphenoidal surgery for pituitary adenomas, 196 experienced postoperative diabetes insipidus. The sinking depth of the diaphragma sellae and the difference between the preoperative and postoperative pituitary stalk deviation angles in the diabetes insipidus group were greater than those in the non-diabetes insipidus group. Logistic regression analysis showed that the risk of diabetes insipidus after transsphenoidal surgery was higher in patients with a larger difference in their pituitary stalk deviation angles (odds ratio = 2.407, 95% CI = 1.335-4.342; P = 0.004). Conclusion: The difference in the pituitary stalk deviation angle could predict the onset of diabetes insipidus after transsphenoidal surgery for pituitary adenomas.

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling.

CONTEXT: Chlorogenic acid (CGA) has good antioxidant effects, but its explicit mechanism in cerebral ischaemia-reperfusion injury is still uncertain. OBJECTIVE: We studied the effect of CGA in human brain microvascular endothelial cells (HBMECs) under OGD/R damage. MATERIALS AND METHODS: HBMECs in 4 groups were treated with oxygen-glucose deprivation/re-oxygenation (OGD/R) (4 + 24 h), normal no CGA treatment and different concentrations (20, 40 or 80 µM) of CGA. Male C57BL/6J mice were classified as sham, middle cerebral artery occlusion (MCAO), and MCAO + CGA (30 mg/kg/day) groups. Mice in the sham group were not subjected to MCAO. Cell viability, apoptosis, angiogenesis and related protein levels were investigated by CCK-8, flow cytometry, TUNEL staining, tube formation and western blot assays. Infarct volume of brain tissues was analyzed by TTC staining. RESULTS: CGA curbed apoptosis (from 32.87% to 13.12% in flow cytometry; from 34.46% to 17.8% in TUNEL assay) but accelerated cell angiogenesis of HBMECs with OGD/R treatment. Moreover, CGA augmented activation of the PI3K-Akt signalling (p-PI3K/PI3K level, from 0.39 to 0.49; p-Akt/Akt level, from 0.52 to 0.81), and the effect of CGA on apoptosis and angiogenesis was abolished by an inhibitor of PI3K-Akt signalling. Furthermore, CGA attenuated infarct (from 41.26% to 22.21%) and apoptosis and promoted angiogenesis and activation of the PI3K/Akt signalling in MCAO-induced mice. CONCLUSIONS: CGA effectively repressed apoptosis and promoted angiogenesis in OGD/R-treated HBMECs and MCAO-treated mice by modulating PI3K-Akt signalling. Our research provides a theoretical basis for the use of CGA in the treatment of ischaemic stroke.

Chlorogenic Acid Prevents Microglia-Induced Neuronal Apoptosis and Oxidative Stress under Hypoxia-Ischemia Environment by Regulating the MIR497HG/miR-29b-3p/SIRT1 Axis.

Background: Chlorogenic acid (CGA) is a polyphenolic compound with antioxidant and anti-inflammatory properties. CGA has been shown to improve neuroinflammation. This study is aimed at elucidating the exact mechanism by which CGA reduces neuroinflammation. Methods: Oxygen and glucose deprivation (OGD) was utilized to treat BV2 microglia and HT-22 hippocampal neurons to engineer an in vitro model of hypoxic ischemia reperfusion. The levels of inflammatory factors (IL-1ß, IL-6, TNF-α, IL-4, and IL-10) and oxidative stress factors (MDA, SOD, and GSH-PX) in microglia were determined by ELISA kits. The neuron proliferation was assessed by CCK-8 assay, and LDH kit was used to determine LDH release in neurons. The fluorescent dye DCF-DA was employed to measure ROS levels in neurons. Correlation of MIR497HG, miR-29b-3p, and SIRT1/NF-κB in neurons and microglia was determined by qRT-PCR. Expressions of inflammatory proteins (COX2, iNOS), oxidative stress pathways (Nrf2, HO-1), and apoptosis-related proteins (Bcl-2, Bax, caspase3, caspase8, and caspase9) in microglia or neurons were determined by western blot. The interactions between MIR497HG and miR-29b-3p, as well as between miR-29b-3p and SIRT1, were determined by dual luciferase assay and RIP assay. Results: CGA attenuated OGD-mediated inflammation and oxidative stress in microglia and inhibited microglia-mediated neuronal apoptosis. CGA increased the levels of MIR497HG and SIRT1 and suppressed the levels of miR-29b-3p in BV2 and HT-22 cells. MIR497HG knockdown, miR-29b-3p upregulation, and SIRT1 inhibition inhibited CGA-mediated anti-inflammatory and neuronal protective functions. There is a targeting correlation between MIR497HG, miR-29b-3p, and Sirt1. MIR497HG sponges miR-29b-3p to regulate SIRT1 expression in an indirect manner. Conclusion: CGA upregulates MIR497HG to curb miR-29b-3p expression, hence initiating the SIRT1/NF-κB signaling pathway and repressing OGD-elicited inflammation, oxidative stress, and neuron apoptosis.

The Difference Between Preoperative and Postoperative Pituitary Stalk Deviation Angles Can Predict Delayed Hyponatremia After Transsphenoidal Surgery.

OBJECTIVE: Our aim was to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of the difference between preoperative and postoperative pituitary stalk deviation angles on delayed hyponatremia. METHODS: A retrospective study was performed on the clinical data of patients with pituitary adenomas who were treated with TSS at a single institution. On the basis of the observation of indicators such as pituitary stalk deviation angle and length of "measurable pituitary stalk" on magnetic resonance imaging, we determined the predictors of postoperative delayed hyponatremia through univariate and multivariate analyses. RESULTS: Microscopic TSS was performed in 422 patients with pituitary adenoma, of whom 66 experienced postoperative delayed hyponatremia. Logistic regression analysis showed that the risk of delayed hyponatremia was greater for patients with a large difference between preoperative and postoperative pituitary stalk deviation angle (odds ratio = 1.040, 95% confidence interval: 1.018-1.051; P < 0.001) and a large difference in the "measurable pituitary stalk" (odds ratio = 1.128, 95% confidence interval: 1.011-1.258; P = 0.032), and patients with high blood sodium on the second day after surgery have a lower probability of developing delayed hyponatremia. CONCLUSIONS: This study is the first to suggest the important role of the difference between preoperative and postoperative pituitary stalk deviation angles in predicting the development of delayed hyponatremia after TSS for pituitary adenomas.

Long noncoding RNA NEAT 1 and its target microRNA-125a in sepsis: Correlation with acute respiratory distress syndrome risk, biochemical indexes, disease severity, and 28-day mortality.

BACKGROUND: Sepsis is one of the main contributors to in-hospital deaths. This study aimed to evaluate the clinical roles of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) and microRNA (miR)-125a in sepsis. METHODS: LncRNA NEAT1 and miR-125a in plasma samples from 102 sepsis patients and 100 healthy controls (HCs) were detected by reverse transcription-quantitative polymerase chain reaction. In sepsis patients, general disease severity was assessed by acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score. Meanwhile, acute respiratory distress syndrome (ARDS) occurrence and mortality during 28 days were recorded. RESULTS: LncRNA NEAT1 was increased, but miR-125a was decreased in sepsis patients compared to HCs, and in ARDS sepsis patients compared to non-ARDS sepsis patients. The receiver's operative characteristic (ROC) curves revealed that higher lncRNA NEAT1 or lower miR-125a had certain predictive value for ARDS risk. Further multivariate logistic regression revealed miR-125a but not lncRNA NEAT1 was correlated with ARDS risk independently in sepsis patients. Additionally, lncRNA NEAT1 was positively, but miR-125a was negatively correlated with APACHE II score and SOFA score in sepsis patients. Moreover, higher lncRNA NEAT1 and lower miR-125a were observed in 28-day deaths compared to 28-day survivors and were correlated with increased accumulating mortality in sepsis patients. CONCLUSION: LncRNA NEAT1 high expression and miR-125a low expression correlate with increased ARDS risk, enhanced disease severity, higher 28-day mortality, and negatively associate with each other in sepsis patients.

Efficient travelling-mode quantum key agreement against participant's attacks.

Quantum key agreement (QKA) is to negotiate a final key among several participants fairly and securely. In this paper, we show that some existing travelling-mode multiparty QKA protocols are vulnerable to internal participant's attacks. Dishonest participants can exploit a favorable geographical location or collude with other participants to predetermine the final keys without being discovered. To resist such attacks, we propose a new travelling-mode multiparty QKA protocol based on non-orthogonal Bell states. Theoretical analysis shows that the proposed protocol is secure against both external and internal attacks, and can achieve higher efficiency compared with existing travelling-mode multiparty QKA protocols. Finally we design an optical platform for each participant, and show that our proposed protocol is feasible with current technologies.

Hyperbaric oxygen promotes neural stem cell proliferation by activating vascular endothelial growth factor/extracellular signal-regulated kinase signaling after traumatic brain injury.

Hyperbaric oxygen (HBO) therapy and neural stem cell (NSC) transplantation can improve traumatic brain injury (TBI) clinically. This study aimed to investigate the mechanism of HBO promoting NSC proliferation and neurological recovery after TBI. Twenty-four Sprague-Dawley rats were divided randomly into three groups: a sham group, a TBI group (constructed using Feeney's free-fall method), and an HBO-treated TBI group. Neurological function was evaluated by Neurological Severity Scores on days 1, 3, and 7, and we found that TBI-induced poor neurological function was improved by HBO. On day 7 after TBI, we observed that TBI promoted NSC proliferation, migration to the lesion area, and the levels of vascular endothelial growth factor (VEGF), VEGFR2, Raf-1, MEK1/2, and phospho-extracellular signal-regulated kinase (ERK) 1/2 protein, which were further boosted by HBO, from immunohistochemistry, immunofluorescence, and Western blot experiments. In vitro, cell injury was applied to NSCs isolated from neonatal Sprague-Dawley rats by the Cell Injury Controller II system. Moreover, data from the BrdU Kit and Western blot showed that in-vitro HBO significantly accelerated NSC proliferation and the levels of proteins related to cell cycle and the VEGF/ERK pathway after cell injury, which was suppressed by the VEGFR2 inhibitor. Taken together, this study indicated that HBO may promote NSC proliferation by activating VEGF/ERK signaling and play a crucial role in neuroprotection after TBI.