Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION: The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.

A combined risk model for the multi-encompassing identification of heterogeneities of prognoses, biological pathway variations and immune states for sepsis patients.

BACKGROUND: Sepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy. METHODS: We systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8). RESULTS: Datasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P < 0.05). The above results indicated that the models in this study are all superior to the traditional biomarkers for the predicting the prognosis of sepsis patients. Furthermore, the current study provides some therapeutic recommendations for patients with high risk scores identified by the three submodels. CONCLUSIONS: In summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.

New Cyclic Diarylheptanoids from Platycarya strobilacea.

Five new cyclic diarylheptanoids (platycary A-E, compounds 1-5) and three previously identified analogues (i.e., phttyearynol (compound 6), myricatomentogenin (compound 7), and juglanin D (compound 8)) were isolated from the stem bark of Platycarya strobilacea. The structures of these compounds were determined using NMR, HRESIMS, and electronic circular dichroism (ECD) data. The cytotoxicity of compounds 1-5 and their ability to inhibit nitric oxide (NO) production, as well as protect against the corticosterone-induced apoptosis of Pheochromocytoma (PC12) cells, were evaluated in vitro using the appropriate bioassays. Compounds 1 and 2 significantly inhibited the corticosterone-induced apoptosis of PC12 cells at a concentration of 20 µΜ.

Piezo1 mediates neuron oxygen-glucose deprivation/reoxygenation injury via Ca2+/calpain signaling.

OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.

Clathrin-mediated endocytosis is required for ANE 30-100K-induced autophagy.

BACKGROUND: We identified an autophagy-inducing areca nut (AN) ingredient (AIAI) in the 30-100 kDa fraction of AN extract (ANE 30-100K). This study was to analyze the role of endocytosis in ANE 30-100K-induced autophagy. METHODS: We used benzyl alcohol, dynasore, and shRNA of clathrin and dynamin to assess whether ANE 30-100K-induced cytotoxicity and accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II were affected in oral (OECM-1) and esophageal (CE81T/VGH) carcinoma cells. RESULTS: Both benzyl alcohol and dynasore effectively reduced ANE 30-100K-induced cytotoxicity and LC3-II accumulation in OECM-1 and CE81T/VGH cells. Downregulated protein expression of both clathrin and dynamin by their shRNA also significantly attenuated ANE 30-100K-induced elevation of LC3-II levels in CE81T/VGH cells. CONCLUSIONS: These results indicate that AIAI may be engulfed by cells through clathrin-mediated endocytosis, which promotes the execution of the following autophagy program.

The combination of blue dye and radioisotope versus radioisotope alone during sentinel lymph node biopsy for breast cancer: a systematic review.

BACKGROUND: The combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes (SLNs) in patients with breast cancer. However, some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs. We performed a systematic review to investigate the added value of blue dye in addition to radioisotope. METHODS: We searched Pubmed and Embase. Prospective studies that compared the combination of radioisotope and blue dye with radioisotope alone were selected. The identification rate of SLNs and the false-negative rate were the main outcomes of interest. The odds ratios (ORs) and 95% confidential intervals (CIs) were calculated by using random-effects model. RESULTS: Twenty-four studies were included. The combination of radioisotope and blue dye showed higher identification rate than radioisotope alone (OR = 2.03, 95% CI 1.53-2.69, P < 0.05). However, no statistically significant difference was revealed for patients after neoadjuvant chemotherapy (OR = 1.64, 95% CI 0.82-3.27, P > 0.05), or for studies with high proportion of patients with positive lymphoscintigraphy (OR = 1.41, 95% CI 0.83-2.39, P > 0.05). Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95% CI 0.44-1.29, P > 0.05). CONCLUSIONS: Although the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection, the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy. Besides, the combined modality did not help lower the false-negative rate.

An open air research study of blast-induced traumatic brain injury to goats.

PURPOSE: We once reported blast-induced traumatic brain injury (bTBI) in confined space. Here, bTBI was studied again on goats in the open air using 3.0 kg trinitrotoluene. METHODS: The goats were placed at 2, 4, 6 and 8 m far from explosion center. Trinitrotoluene (TNT) was used as the source of the blast wave and the pressure at each distance was recorded. The systemic physiology, electroencephalogram, serum level of S-100 beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 h after the exposure. RESULTS: Simple blast waveforms were recorded with parameters of 702.8 kPa-0.442 ms, 148.4 kPa-2.503 ms, 73.9 kPa-3.233 ms, and 41.9 kPa-5.898 ms at 2, 4, 6 and 8 m respectively. Encephalic blast overpressure was on the first time recorded in the literature by us at 104.2 kPa-0.60 ms at 2 m, where mortality and burn rate were 44% and 44%. Gross examination showed that bTBI was mainly manifested as congestive expansion of blood vessels and subarachnoid hemorrhage, which had a total incidence of 25% and 19% in 36 goats. Microscopical observation found that the main pathohistological changes were enlarged perivascular space (21/36, 58%), small hemorrhages (9/36, 25%), vascular dilatation and congestion (8/36, 22%), and less subarachnoid hemorrhage (2/36, 6%). After explosion, serum levels of S-100b and NSE were elevated, and EEG changed into slow frequency with declined amplitude. The results indicated that severity and incidence of bTBI is related to the intensity of blast overpressure. CONCLUSION: Blast wave can pass through the skull to directly injure brain tissue.

Resin glycosides from Porana duclouxii.

A new intact resin glycoside (3) and two glycosidic acids (1 and 2), all having a common trisaccharide moiety and (11S)-hydroxytetradecanoic acid or (3S,11S)-dihydroxytetradecanoic acid as the aglycone, were obtained from the roots of Porana duclouxii. Their structures were elucidated by spectroscopic analyses and chemical correlations. These compounds represent the first examples of resin glycosides from the genus Porana.

Antisense oligonucleotides targeting basal forebrain ATXN2 enhances spatial memory and ameliorates sleep deprivation-induced fear memory impairment in mice.

INTRODUCTION: Regulation of brain-derived neurotrophic factor (BDNF) in the basal forebrain ameliorates sleep deprivation-induced fear memory impairments in rodents. Antisense oligonucleotides (ASOs) targeting ATXN2 was a potential therapy for spinocerebellar ataxia, whose pathogenic mechanism associates with reduced BDNF expression. We tested the hypothesis that ASO7 targeting ATXN2 could affect BDNF levels in mouse basal forebrain and ameliorate sleep deprivation-induced fear memory impairments. METHODS: Adult male C57BL/6 mice were used to evaluate the effects of ASO7 targeting ATXN2 microinjected into the bilateral basal forebrain (1 µg, 0.5 µL, each side) on spatial memory, fear memory and sleep deprivation-induced fear memory impairments. Spatial memory and fear memory were detected by the Morris water maze and step-down inhibitory avoidance test, respectively. Immunohistochemistry, RT-PCR, and Western blot were used to evaluate the changes of levels of BDNF, ATXN2, and postsynaptic density 95 (PSD95) protein as well as ATXN2 mRNA. The morphological changes in neurons in the hippocampal CA1 region were detected by HE staining and Nissl staining. RESULTS: ASO7 targeting ATXN2 microinjected into the basal forebrain could suppress ATXN2 mRNA and protein expression for more than 1 month and enhance spatial memory but not fear memory in mice. BDNF mRNA and protein expression in basal forebrain and hippocampus was increased by ASO7. Moreover, PSD95 expression and synapse formation were increased in the hippocampus. Furthermore, ASO7 microinjected into the basal forebrain increased BDNF and PSD95 protein expression in the basal forebrain of sleep-deprived mice and counteracted sleep deprivation-induced fear memory impairments. CONCLUSION: ASOs targeting ATXN2 may provide effective interventions for sleep deprivation-induced cognitive impairments.

Cochlear implantation in a patient with congenital microtia, cochlear hypoplasia, venous anomalies of the temporal bone and laryngomalacia: Challenges and surgical considerations.

RATIONALE AND PATIENT CONCERNS: Congenital hearing loss is often caused by an inner ear malformation, in such cases, the presence of other anomalies, such as microtia, and venous anomalies of the temporal bone and laryngomalacia makes it challenging to perform cochlear implantation surgery. DIAGNOSES: This study reports the case of a 28-month-old girl with congenital profound hearing loss, laryngomalacia, and malformed inner ear, who received cochlear implantation surgery. The bony structure, vessels and nerves were first assessed through magnetic resonance imaging and computed tomography before exploring the genetic basis of the condition using trio-based whole exome sequencing. Perioperative evaluation and management of the airway was then performed by experienced anesthesiologist, with the surgical challenges as well as problems encountered fully evaluated. INTERVENTIONS: Cochlear implantation was eventually performed using a trans-mastoid approach under uneventful general anesthesia. OUTCOMES: Due to the small size of the cochlea, a short electrode FLEX24 was inserted through the cochleostomy. LESSONS: Considering the high risk of facial nerve injury and limited access to the cochlea when patients present significant bony and venous anomalies, cochlear implantation in such patients require careful preoperative evaluation and thoughtful planning. In these cases, airway assessment, magnetic resonance venography, magnetic resonance arteriography, and magnetic resonance imaging and computed tomography can be useful to minimize the risks. Intraoperative facial nerve monitoring is also recommended to assist in the safe location of facial nerve.

Accuracy of Artificial Intelligence-Based Photographic Detection of Gingivitis.

OBJECTIVES: Gingivitis is one of the most prevalent plaque-initiated dental diseases globally. It is challenging to maintain satisfactory plaque control without continuous professional advice. Artificial intelligence may be used to provide automated visual plaque control advice based on intraoral photographs. METHODS: Frontal view intraoral photographs fulfilling selection criteria were collected. Along the gingival margin, the gingival conditions of individual sites were labelled as healthy, diseased, or questionable. Photographs were randomly assigned as training or validation datasets. Training datasets were input into a novel artificial intelligence system and its accuracy in detection of gingivitis including sensitivity, specificity, and mean intersection-over-union were analysed using validation dataset. The accuracy was reported according to STARD-2015 statement. RESULTS: A total of 567 intraoral photographs were collected and labelled, of which 80% were used for training and 20% for validation. Regarding training datasets, there were total 113,745,208 pixels with 9,270,413; 5,711,027; and 4,596,612 pixels were labelled as healthy, diseased, and questionable respectively. Regarding validation datasets, there were 28,319,607 pixels with 1,732,031; 1,866,104; and 1,116,493 pixels were labelled as healthy, diseased, and questionable, respectively. AI correctly predicted 1,114,623 healthy and 1,183,718 diseased pixels with sensitivity of 0.92 and specificity of 0.94. The mean intersection-over-union of the system was 0.60 and above the commonly accepted threshold of 0.50. CONCLUSIONS: Artificial intelligence could identify specific sites with and without gingival inflammation, with high sensitivity and high specificity that are on par with visual examination by human dentist. This system may be used for monitoring of the effectiveness of patients' plaque control.

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis.

Background: Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2'-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators can be a diagnostic marker and potential drug therapy target of early pulmonary fibrosis needs to be explored. Materials and Methods: Using GSE110147 and GSE33566 in the GEO database to predict the m6A methylation regulators that may be related to the development of pulmonary fibrosis, we used 10 mg/ml bleomycin to induce mouse pulmonary fibrosis models and human pulmonary fibrosis samples, to confirm whether this indicator can be an early diagnostic marker of pulmonary fibrosis. Results: According to the database prediction results, METTL3 can predict the occurrence and development of pulmonary fibrosis, and the results of MASSON and HE staining show that the fibrosis model of mice is successful, and the fibrosis of human samples is obvious. The results of immunohistochemistry showed that the expression of METTL3 was significantly reduced in pulmonary fibrosis. Conclusions: The m6A methylation regulator METTL3 can be considered as an important biomarker for diagnosing pulmonary fibrosis occurrence, furthermore it could be considered as a drug target because of its low expression in pulmonary fibrosis.

Inhibition of Piezo1/Ca2+/calpain signaling in the rat basal forebrain reverses sleep deprivation-induced fear memory impairments.

In this study, we tested the hypothesis that the Piezo1/Ca2+/calpain pathway of the basal forebrain (BF) modulates impaired fear conditioning caused by sleep deprivation. Adult male Wistar rats were subjected to 6 h of total sleep deprivation using the gentle handling protocol. Step-down inhibitory avoidance tests revealed that sleep deprivation induced substantial short- and long-term fear memory impairment in rats, which was accompanied by increased Piezo1 protein expression (P < 0.01) and increased cleavage of full-length tropomyocin receptor kinase B (TrkB-FL) (P < 0.01) in the BF area. Microinjection of the Piezo1 activator Yoda1 into the BF mimicked these sleep deprivation-induced phenomena; TrkB-FL cleavage was increased (P < 0.01) and short- and long-term fear memory was impaired (both P < 0.01) by Yoda1. Inhibition of Piezo1 by GsMTx4 in the BF area reduced TrkB-FL degradation (P < 0.01) and partially reversed short- and long-term fear memory impairments in sleep-deprived rats (both P < 0.01). Inhibition of calpain activation, downstream of Piezo1 signaling, also improved short- and long-term fear memory impairments (P = 0.038, P = 0.011) and reduced TrkB degradation (P < 0.01) in sleep-deprived rats. Moreover, sleep deprivation induced a lower pain threshold than the rest control, which was partly reversed by microinjection of GsMTx4 or PD151746. Neither sleep deprivation nor the abovementioned drugs affected locomotion and sedation. Taken together, these results indicate that BF Piezo1/Ca2+/calpain signaling plays a role in sleep deprivation-induced TrkB signaling disruption and fear memory impairments in rats.

Development and validation of a risk score for predicting postoperative delirium after major abdominal surgery by incorporating preoperative risk factors and surgical Apgar score.

STUDY OBJECTIVE: To develop and validate a simple delirium-predicting scoring system in patients undergoing major abdominal surgery by incorporating preoperative risk factors and intraoperative surgical Apgar score (SAS). DESIGN: Observational retrospective cohort study. SETTING: A tertiary general hospital in China. PATIENTS: 1055 patients who received major abdominal surgery from January 2015 to December 2019. MEASUREMENTS: We collected data on preoperative and intraoperative variables, and postoperative delirium. A risk scoring system for postoperative delirium in patients after major open abdominal surgery was developed and validated based on traditional logistic regression model. The elastic net algorithm was further developed and evaluated. MAIN RESULTS: The incidence of postoperative delirium was 17.8% (188/1055) in these patients. They were randomly divided into the development (n = 713) and validation (n = 342) cohorts. Both the logistic regression model and the elastic net regression model identified that advanced age, arrythmia, hypoalbuminemia, coagulation dysfunction, mental illness or cognitive impairments and low surgical Apgar score are related with increased risk of postoperative delirium. The elastic net algorithm has an area under the receiver operating characteristic curve (AUROC) of 0.842 and 0.822 in the development and validation cohorts, respectively. A prognostic score was calculated using the following formula: Prognostic score = Age classification (0 to 3 points) + arrythmia + 2 * hypoalbuminemia + 2 * coagulation dysfunction + 4 * mental illness or cognitive impairments + (10-surgical Apgar score). The 22-point risk scoring system had good discrimination and calibration with an AUROC of 0.823 and 0.834, and a non-significant Hosmer-Lemeshow test P = 0.317 and P = 0.853 in the development and validation cohorts, respectively. The bootstrapping internal verification method (R = 1000) yielded a C-index of 0.822 (95% CI: 0.759-0.857). CONCLUSION: The prognostic scoring system, which used both preoperative risk factors and surgical Apgar score, serves as a good first step toward a clinically useful predictive model for postoperative delirium in patients undergoing major open abdominal surgery.

[The clinical efficacy and cardiac safety of itraconazole injection in treatment of acute pulmonary invasive fungal infection in chronic pulmonary diseases in the elderly].

OBJECTIVE: To observe the clinical efficiency and cardiac safety of itraconazole injection in the treatment of the elderly patients with chronic pulmonary diseases suffered from acute pulmonary invasive fungal infection (IFI). METHODS: The research was single centre and open experimental designed trial. We selected patients (> 70 years old) who were admitted to our department of respiratory medicine because of chronic pulmonary diseases combined with pulmonary IFI. All patients received intravenous itraconazole injection. The clinical efficiency and cardiac safety was observed for 14 days. RESULTS: Thirty-five patients were included, 3 patients were proven, 32 patients were probable. There were 26 patients combined with coronary artery disease (74.28%), 20 patients combined with cor pulmonale (57.14%), and 17 patients simultaneously combined with both (48.57%). The temperature of 22 patients (62.86%) decreased to normal in 7 days, 31 patients (90.39%) in 11 days. After 14 days' therapy, the level of 1, 3-beta-D glucan decreased to normal in 26 patients (78.79%). The foci in sternum of 5 patients who were infected by candida albicans were completely absorbed in 14 days. Two patients were suffered from left heart insufficiency and arrhythmia ventricular on the 4th and 5th day respectively, and disappeared on the next day after given symptomatic treatment. There was a significant difference in B-type natriuretic peptide (BNP) between before and after treatment. CONCLUSION: The clinical efficiency of itraconazole injection in the elderly patients who suffered from chronic pulmonary diseases and then combined with acute pulmonary IFI were 78.79%. Even if combined with coronary artery disease and/or cor pulmonale, the elderly patients who have chronic pulmonary diseases were safe when using the itraconazole injection in 14 days.

Active control on topological immunity of elastic wave metamaterials.

The topology concept in the condensed physics and acoustics is introduced into the elastic wave metamaterial plate, which can show the topological property of the flexural wave. The elastic wave metamaterial plate consists of the hexagonal array which is connected by the piezoelectric shunting circuits. The Dirac point is found by adjusting the size of the unit cell and numerical simulations are illustrated to show the topological immunity. Then the closing and breaking of the Dirac point can be generated by the negative capacitance circuits. These investigations denote that the topological immunity can be achieved for flexural wave in mechanical metamaterial plate. The experiments with the active control action are finally carried out to support the numerical design.

Activation of brain-derived neurotrophic factor signaling in the basal forebrain reverses acute sleep deprivation-induced fear memory impairments.

INTRODUCTION: The mechanisms underlying sleep deprivation-induced memory impairments and relevant compensatory signaling pathways remain elusive. We tested the hypothesis that increased brain-derived neurotrophic factor (BDNF) expression in the basal forebrain following acute sleep deprivation was a compensatory mechanism to maintain fear memory performance. METHODS: Adult male Wistar rats were deprived of 6-hr total sleep from the beginning of the light cycle. The effects of sleep deprivation on BDNF protein expression and activation of downstream tropomyosin receptor kinase B (TrkB)/phospholipase C-γ1 (PLCγ1) signaling in the basal forebrain and fear memory consolidation were examined. BDNF or selective downstream TrkB receptor antagonist ANA-12 was further injected into the basal forebrain bilaterally to observe the changes in fear memory consolidation in response to modulation of the BDNF/TrkB signaling. RESULTS: Six hours of sleep deprivation-induced both short- and long-term fear memory impairments. Increased BDNF protein expression and TrkB and PLCγ1 phosphorylation in the basal forebrain were observed after sleep deprivation. Microinjection of BDNF into the basal forebrain partly reversed fear memory deficits caused by sleep deprivation, which were accompanied by increased BDNF protein levels and TrkB/PLCγ1 activation. After ANA-12 microinjection, sleep deprivation-induced activation of the BDNF/TrkB pathway was inhibited and impairments of fear memory consolidation were further aggravated. CONCLUSIONS: Acute sleep deprivation induces compensatory increase of BDNF expression in the basal forebrain. Microinjection of BDNF into the basal forebrain mitigates the fear memory impairments caused by sleep deprivation by activating TrkB/PLCγ1 signaling.

Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial-mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-ß1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-ß1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-ß1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.

Active control on switchable waveguide of elastic wave metamaterials with the 3D printing technology.

Propagation of elastic waves along a direction has special interests in practical applications. These concerns generate the design of an elastic wave metamaterial with electrically switchable properties, which is studied in this work. The structure contains a T-shaped waveguide in a plate with the 3D printing technology; and the active control system is used to tune the propagation direction of the flexural wave. The piezoelectric patches which are connected by the negative capacitance circuits are applied to behave as the active control system. The finite element simulation is performed to give the theoretical prediction of the switchable waveguide and the tunable equivalent parameters are achieved by the electrical circuits. The active control experiments are finally carried out to support the numerical design.