Jasmonates regulate apical hook development by repressing brassinosteroid biosynthesis and signaling.

An apical hook is a special structure formed during skotomorphogenesis in dicotyledonous plant species. It is critical for protecting the shoot apical meristem from mechanical damage during seed germination and hypocotyl elongation in soil. Brassinosteroid (BR) and jasmonate (JA) phytohormones antagonistically regulate apical hook formation. However, the interrelationship between BRs and JAs in this process has not been well elucidated. Here, we reveal that JAs repress BRs to regulate apical hook development in Arabidopsis (Arabidopsis thaliana). Exogenous application of methyl jasmonate (MeJA) repressed the expression of the rate-limiting BR biosynthetic gene DWARF4 (DWF4) in a process relying on 3 key JA-dependent transcription factors, MYC2, MYC3, and MYC4. We demonstrated that MYC2 interacts with the critical BR-activated transcription factor BRASSINAZOLE RESISTANT 1 (BZR1), disrupting the association of BZR1 with its partner transcription factors, such as those of the PHYTOCHROME INTERACTING FACTOR (PIF) family and downregulating the expression of their target genes, such as WAVY ROOT GROWTH 2 (WAG2), encoding a protein kinase essential for apical hook development. Our results indicate that JAs not only repress the expression of BR biosynthetic gene DWF4 but, more importantly, attenuate BR signaling by inhibiting the transcriptional activation of BZR1 by MYC2 during apical hook development.

EGR1 knockdown confers protection against ferroptosis and ameliorates intervertebral disc cartilage degeneration by inactivating the MAP3K14/NF-κB axis.

This study explored whether EGR1-MAP3K14-NF-κB axis regulated ferroptosis and IVD cartilage generation. EGR1 and MAP3K14 expression levels were determined in CEP tissues of IVDD patients and intermittent cyclic mechanical tension (ICMT)-treated CEP cells. After EGR1 and MAP3K14 were altered in ICMT-treated CEP cells, the expression levels of degeneration- and ferroptosis-related proteins were measured. Binding relationship between EGR1 and MAP3K14 was evaluated. Additionally, the impacts of EFR1 knockdown on ferroptosis and cartilage degeneration in vivo were analyzed. EGR1 and MAP3K14 were overexpressed in clinical samples and cell models of IVDD. In IVDD cell models, EGR1 knockdown reduced ferroptosis and cartilage degeneration, which was reversed by MAP3K14 overexpression or Erastin treatment. NF-κB pathway inhibition nullified these effects of sh-EGR1 + oe-MAP3K14 treatment. EGR1 knockdown inhibited ferroptosis and relieved CEP degeneration via MAP3K14-NF-κB axis inactivation in vivo. Collectively, our findings highlighted that EGR1 promoted ferroptosis and IVD cartilage degeneration through MAP3K14-NF-κB axis.

Co-Doped Porous Carbon/Carbon Nanotube Heterostructures Derived from ZIF-L@ZIF-67 for Efficient Microwave Absorption.

Carbon-based magnetic metal composites derived from metal-organic frameworks (MOFs) are promising materials for the preparation of broadband microwave absorbers. In this work, the leaf-like co-doped porous carbon/carbon nanotube heterostructure was obtained using ZIF-L@ZIF-67 as precursor. The number of carbon nanotubes can be controlled by varying the amount of ZIF-67, thus regulating the dielectric constant of the sample. An optimum reflection loss of -42.2 dB is attained when ZIF-67 is added at 2 mmol. An effective absorption bandwidth (EAB) of 4.8 GHz is achieved with a thickness of 2.2 mm and a filler weight of 12%. The excellent microwave absorption (MA) ability is generated from the mesopore structure, uniform heterogeneous interfaces, and high conduction loss. The work offers useful guidelines to devise and prepare such nanostructured materials for MA materials.

Vegetation clumping modulates global photosynthesis through adjusting canopy light environment.

The spatial dispersion of photoelements within a vegetation canopy, quantified by the clumping index (CI), directly regulates the within-canopy light environment and photosynthesis rate, but is not commonly implemented in terrestrial biosphere models to estimate the ecosystem carbon cycle. A few global CI products have been developed recently with remote sensing measurements, making it possible to examine the global impacts of CI. This study deployed CI in the radiative transfer scheme of the Community Land Model version 5 (CLM5) and used the revised CLM5 to quantitatively evaluate the extent to which CI can affect canopy absorbed radiation and gross primary production (GPP), and for the first time, considering the uncertainty and seasonal variation of CI with multiple remote sensing products. Compared to the results without considering the CI impact, the revised CLM5 estimated that sunlit canopy absorbed up to 9%-15% and 23%-34% less direct and diffuse radiation, respectively, while shaded canopy absorbed 3%-18% more diffuse radiation across different biome types. The CI impacts on canopy light conditions included changes in canopy light absorption, and sunlit-shaded leaf area fraction related to nitrogen distribution and thus the maximum rate of Rubisco carboxylase activity (Vcmax ), which together decreased photosynthesis in sunlit canopy by 5.9-7.2 PgC year-1 while enhanced photosynthesis by 6.9-8.2 PgC year-1 in shaded canopy. With higher light use efficiency of shaded leaves, shaded canopy increased photosynthesis compensated and exceeded the lost photosynthesis in sunlit canopy, resulting in 1.0 ± 0.12 PgC year-1 net increase in GPP. The uncertainty of GPP due to the different input CI datasets was much larger than that caused by CI seasonal variations, and was up to 50% of the magnitude of GPP interannual variations in the tropical regions. This study highlights the necessity of considering the impacts of CI and its uncertainty in terrestrial biosphere models.

MiR-155-5p Aggravated Astrocyte Activation and Glial Scarring in a Spinal Cord Injury Model by Inhibiting Ndfip1 Expression and PTEN Nuclear Translocation.

Central nervous injury and regeneration repair have always been a hot and difficult scientific questions in neuroscience, such as spinal cord injury (SCI) caused by a traffic accident, fall injury, and war. After SCI, astrocytes further migrate to the injured area and form dense glial scar through proliferation, which not only limits the infiltration of inflammatory cells but also affects axon regeneration. We aim to explore the effect and underlying mechanism of miR-155-5p overexpression promoted astrocyte activation and glial scarring in an SCI model. MiR-155-5p mimic (50 or 100 nm) was used to transfect CTX-TNA2 rat brain primary astrocyte cell line. MiR-155-5p antagonist and miR-155-5p agomir were performed to treat SCI rats. MiR-155-5p mimic dose-dependently promoted astrocyte proliferation, and inhibited cell apoptosis. MiR-155-5p overexpression inhibited nuclear PTEN expression by targeting Nedd4 family interacting protein 1 (Ndfip1). Ndfip1 overexpression reversed astrocyte activation which was induced by miR-155-5p mimic. Meanwhile, Ndfip1 overexpression abolished the inhibition effect of miR-155-5p mimic on PTEN nuclear translocation. In vivo, miR-155-5p silencing improved SCI rat locomotor function and promoted astrocyte activation and glial scar formation. And miR-155-5p overexpression showed the opposite results. MiR-155-5p aggravated astrocyte activation and glial scarring in a SCI model by targeting Ndfip1 expression and inhibiting PTEN nuclear translocation. These findings have ramifications for the development of miRNAs as SCI therapeutics.

Construction and validation of a predictive model for postoperative urinary retention after lumbar interbody fusion surgery.

BACKGROUND: Postoperative urine retention (POUR) after lumbar interbody fusion surgery may lead to recatheterization and prolonged hospitalization. In this study, a predictive model was constructed and validated. The objective was to provide a nomogram for estimating the risk of POUR and then reducing the incidence. METHODS: A total of 423 cases of lumbar fusion surgery were included; 65 of these cases developed POUR, an incidence of 15.4%. The dataset is divided into a training set and a validation set according to time. 18 candidate variables were selected. The candidate variables were screened through LASSO regression. The stepwise regression and random forest analysis were then conducted to construct the predictive model and draw a nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the calibration curve were used to evaluate the predictive effect of the model. RESULTS: The best lambda value in LASSO was 0.025082; according to this, five significant variables were screened, including age, smoking history, surgical method, operative time, and visual analog scale (VAS) score of postoperative low back pain. A predictive model containing four variables was constructed by stepwise regression. The variables included age (ß = 0.047, OR = 1.048), smoking history (ß = 1.950, OR = 7.031), operative time (ß = 0.022, OR = 1.022), and postoperative VAS score of low back pain (ß = 2.554, OR = 12.858). A nomogram was drawn based on the results. The AUC of the ROC curve of the training set was 0.891, the validation set was 0.854 in the stepwise regression model. The calibration curves of the training set and validation set are in good agreement with the actual curves, showing that the stepwise regression model has good prediction ability. The AUC of the training set was 0.996, and that of the verification set was 0.856 in the random forest model. CONCLUSION: This study developed and internally validated a new nomogram and a random forest model for predicting the risk of POUR after lumbar interbody fusion surgery. Both of the nomogram and the random forest model have high accuracy in this study.

Study on Microwave-Assisted Ignition Using a Novel Aero-Engine Combustor.

Microwave plasma can improve the performance of ignition and combustion, as well as reduce pollutant emissions. By designing a novel microwave feeding device, the combustor can be used as a cavity resonator to generate microwave plasma and improve the performance of ignition and combustion. In order to feed the energy of microwave into the combustor as much as possible, and effectively adapt to the change in resonance frequency of combustor during ignition and combustion, the combustor was designed and manufactured by optimizing the size of slot antenna and setting the tuning screws, according to the simulation results of HFSS software (version: 2019 R 3). The relationship between the size, position of metal tip in the combustor and the discharge voltage was studied using HFSS software, as well as the interaction between ignition kernel, flame and microwave. The resonant characteristics of combustor and the discharge of microwave-assisted igniter were subsequently studied via experiments. The results show that the combustor as microwave cavity resonator has a wider resonance curve and can adapt to the change in resonance frequency during ignition and combustion. It is also indicated that microwave can enhance the discharge development of igniter and increase the discharge size. Based on this, the electric and magnetic field effects of microwave are decoupled.

A Novel Ionospheric Disturbance Index to Evaluate the Global Effect on BeiDou Navigation Satellite System Signal Caused by the Moderate Geomagnetic Storm on May 12, 2021.

In this paper, we propose a new method to quantitatively evaluate the quality of the carrier phase observation signals of the BeiDou Navigation Satellite System (BDS) during weak and moderate geomagnetic storms. We take a moderate geomagnetic storm that occurred on 12 May 2021 during the 25th solar cycle as an example. The results show that the newly defined PAS (Percentage of Affected Satellites) index shows significant anomaly changes during the moderate geomagnetic storm. Its variation trend has good correlations with the geomagnetic storm Kp index and Dst index. The anomaly stations are mainly distributed in the equatorial region and auroral region in the northern and southern hemispheres. The proposed PAS index has a good indication for both BDS2 and BDS3 satellites. We further validated this index by calculating the Precise Point Position (PPP) positioning error. We found that the anomaly period of PAS has strong consistency with the abnormal period of PPP positioning accuracy. This study could provide methodological support for the evaluation of the signal quality and analysis of positioning accuracy for the BeiDou satellite navigation system under different space weather conditions.

Comparison of percutaneous endoscopic and open posterior lumbar interbody fusion for the treatment of single-segmental lumbar degenerative diseases.

BACKGROUND: Endoscopic lumbar interbody fusion has become an emerging technique. Some researchers have reported the technique of percutaneous endoscopic transforaminal lumbar interbody fusion. We propose percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) as an alternative approach. The purpose of this study was to assess the clinical efficacy of PE-PLIF by comparing percutaneous endoscopic and open posterior lumbar interbody fusion (PLIF). METHODS: Thirty patients were enrolled in each group. Demographic data, perioperative data, and radiological parameters were collected prospectively. The clinical outcomes were evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. RESULTS: The background data were comparable between the two groups. The mean operation time was longer in the PE-PLIF group. The PE-PLIF group showed benefits in less blood loss and shorter hospital stay. VAS and ODI scores significantly improved in both groups. However, the VAS score of low-back pain was lower in the PE-PLIF group. The satisfaction rate was 96.7% in both groups. The radiological outcomes were similar in both groups. In the PE-PLIF group, the fusion rate was 93.3%, and the cage subsidence rate was 6.7%; in the open PLIF group, the fusion and cage subsidence rates were 96.7% and 16.7%. There were minor complications in one patient in the PE-PLIF group and two in the open PLIF group. CONCLUSIONS: The current study revealed that PE-PLIF is safe and effective compared with open PLIF. In addition, this minimally invasive technique may enhance postoperative recovery by reducing tissue damage and blood loss.

Extraction of Step-Feature Lines in Open-Pit Mines Based on UAV Point-Cloud Data.

Step-feature lines are one of the important geometrical elements for drawing the status quo maps of open-pit mines, and the efficient and accurate automatic extraction and updating of step-feature lines is of great significance for open-pit-mine stripping planning and analysis. In this study, an automatic extraction method of step-feature lines in an open-pit mine based on unmanned-aerial-vehicle (UAV) point-cloud data is proposed. The method is mainly used to solve the key problems, such as low accuracy, local-feature-line loss, and the discontinuity of the step-feature-line extraction method. The method first performs the regular raster resampling of the open-pit-mine cloud based on the MLS algorithm, then extracts the step-feature point set by detecting the elevation-gradient change in the resampled point cloud, further traces the step-feature control nodes by the seed-growth tracking algorithm, and finally generates smooth step-feature lines by fitting the space curve to the step-feature control nodes. The results show that the method effectively improves the accuracy of step-feature-line extraction and solves the problems of local-feature-line loss and discontinuity.

A New Fusicoccane-Type Norditerpene and a New Indone from the Marine-Derived Fungus Aspergillus aculeatinus WHUF0198.

A new norditerpene named aculeaterpene A (1) and a new indone named aculeaindone A (2), along with eight known compounds 3-10 were isolated from the culture extract of Aspergillus aculeatinus WHUF0198. The structural characterization of compounds 1 and 2 were performed by spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments, whereas the absolute configurations were determined by comparing their experimental or calculated ECD spectra. Compound 1 was the first report of fusicoccane-based norditerpene, in which the C-20 was degraded and tured into a hydroxy group.

Percutaneous endoscopic posterior lumbar interbody fusion for the treatment of degenerative lumbar diseases: a technical note and summary of the initial clinical outcomes.

BACKGROUND: Percutaneous endoscopic lumbar interbody fusion was a new technique that leads to improved visualization, improved safety and less trauma than does the traditional procedure. The purpose of this study was to introduce the technique of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and determine its efficacy. METHODS: 35 patients with an average age of 52.3±13.7 years were treated with single-segment PE-PLIF. The perioperative parameters and the radiographic parameters were measured. The visual analog scale (VAS) score for low back pain, VAS score for leg pain and Oswestry disability index (ODI) score were used to assess the levels of pain and function. RESULTS: The mean estimated volume of blood loss was 68.6±32.3 ml, operative time was 179.6±31.0 minutes. PE-PLIF significantly reduced the VAS score for low back pain, VAS score for leg pain and ODI score, and improved the posterior disc height, lumbar lordosis angle and segmental lordosis angle (p < 0.05). The rate of satisfaction was 94.3%. One patient suffered a dural tear. There was one case of contralateral radiculopathy that was relieved after conservative treatment. CONCLUSIONS: This research suggests that PE-PLIF is a minimally invasive, safe, and effective treatment for degenerative lumbar diseases requiring interbody fusion.

Obeticholic Acid Derivative, T-2054 Suppresses Osteoarthritis via Inhibiting NF-κB-Signaling Pathway.

Osteoarthritis (OA), a degenerative joint disorder, has been reported as the most common cause of disability worldwide. The production of inflammatory cytokines is the main factor in OA. Previous studies have been reported that obeticholic acid (OCA) and OCA derivatives inhibited the release of proinflammatory cytokines in acute liver failure, but they have not been studied in the progression of OA. In our study, we screened our small synthetic library of OCA derivatives and found T-2054 had anti-inflammatory properties. Meanwhile, the proliferation of RAW 264.7 cells and ATDC5 cells were not affected by T-2054. T-2054 treatment significantly relieved the release of NO, as well as mRNA and protein expression levels of inflammatory cytokines (IL-6, IL-8 and TNF-α) in LPS-induced RAW 264.7 cells. Moreover, T-2054 promoted extracellular matrix (ECM) synthesis in TNF-α-treated ATDC5 chondrocytes. Moreover, T-2054 could relieve the infiltration of inflammatory cells and degeneration of the cartilage matrix and decrease the levels of serum IL-6, IL-8 and TNF-α in DMM-induced C57BL/6 mice models. At the same time, T-2054 showed no obvious toxicity to mice. Mechanistically, T-2054 decreased the extent of p-p65 expression in LPS-induced RAW 264.7 cells and TNF-α-treated ATDC5 chondrocytes. In summary, we showed for the first time that T-2054 effectively reduced the release of inflammatory mediators, as well as promoted extracellular matrix (ECM) synthesis via the NF-κB-signaling pathway. Our findings support the potential use of T-2054 as an effective therapeutic agent for the treatment of OA.

New Ophiobolins from the Deep-Sea Derived Fungus Aspergillus sp. WHU0154 and Their Anti-Inflammatory Effects.

Deep-sea fungi have become a new arsenal for the discovery of leading compounds. Here five new ophiobolins 1-5, together with six known analogues 6-11, obtained from a deep-sea derived fungus WHU0154. Their structures were determined by analyses of IR, HR-ESI-MS, and NMR spectra, along with experimental and calculated electronic circular dichroism (ECD) analysis. Pharmacological studies showed that compounds 4 and 6 exhibited obvious inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine macrophage RAW264.7 cells. Mechanical study revealed that compound 6 could inhibit the inducible nitric oxide synthase (iNOS) level in LPS-stimulated RAW264.7 cells. In addition, compounds 6, 9, and 10 could significantly inhibit the expression of cyclooxygenase 2 (COX 2) in LPS-induced RAW264.7 cells. Preliminary structure-activity relationship (SAR) analyses revealed that the aldehyde group at C-21 and the α, ß-unsaturated ketone functionality at A ring in ophiobolins were vital for their anti-inflammatory effects. Together, the results demonstrated that ophiobolins, especially for compound 6, exhibited strong anti-inflammatory effects and shed light on the discovery of ophiobolins as new anti-inflammatory agents.

Mechanical and Thermal Properties of Polyether Polytriazole Elastomers Formed by Click-Chemical Reaction Curing Glycidyl Azide Polymer.

Energetic binders are a research hot-spot, and much emphasis has been placed on their mechanical properties. In this study, propargyl-terminated ethylene oxide-tetrahydrofuran copolymer (PTPET) was synthesized. Then, PTPET and low-molecular-weight ester-terminated glycidyl azide polymer (GAP) were reacted by the click reaction without using catalysts to obtain a polyether polytriazole elastomer. Through tensile tests, where R = 0.5, the tensile strength reached 0.332 MPa, with an elongation at break of 897.1%. Swelling tests were used to measure the cross-linked network and showed that the cross-linked network regularity was reduced as R increased. The same conclusions were confirmed by dynamic mechanical analysis (DMA). In DMA curves, Tg was around -70 to -65 °C, and a small amount of crystallization appeared at between -50 and -30 °C, because locally ordered structures were also present in random copolymers, thereby forming localized crystals. Their thermal performance was tested by Differential Scanning Calorimeter (DSC) and Thermal Gravimetric Analyzer (TG), and the main mass loss occurred at around 350 to 450 °C, which meant that they were stable. In conclusion, the polyether polytriazole elastomer can be used as a binder in a composite propellant.

Improved estimates of global terrestrial photosynthesis using information on leaf chlorophyll content.

The terrestrial biosphere plays a critical role in mitigating climate change by absorbing anthropogenic CO2 emissions through photosynthesis. The rate of photosynthesis is determined jointly by environmental variables and the intrinsic photosynthetic capacity of plants (i.e. maximum carboxylation rate; Vcmax25 ). A lack of an effective means to derive spatially and temporally explicit Vcmax25 has long hampered efforts towards estimating global photosynthesis accurately. Recent work suggests that leaf chlorophyll content (Chlleaf ) is strongly related to Vcmax25 , since Chlleaf and Vcmax25 are both correlated with photosynthetic nitrogen content. We used medium resolution satellite images to derive spatially and temporally explicit Chlleaf , which we then used to parameterize Vcmax25 within a terrestrial biosphere model. Modelled photosynthesis estimates were evaluated against measured photosynthesis at 124 eddy covariance sites. The inclusion of Chlleaf in a terrestrial biosphere model improved the spatial and temporal variability of photosynthesis estimates, reducing biases at eddy covariance sites by 8% on average, with the largest improvements occurring for croplands (21% bias reduction) and deciduous forests (15% bias reduction). At the global scale, the inclusion of Chlleaf reduced terrestrial photosynthesis estimates by 9 PgC/year and improved the correlations with a reconstructed solar-induced fluorescence product and a gridded photosynthesis product upscaled from tower measurements. We found positive impacts of Chlleaf on modelled photosynthesis for deciduous forests, croplands, grasslands, savannas and wetlands, but mixed impacts for shrublands and evergreen broadleaf forests and negative impacts for evergreen needleleaf forests and mixed forests. Our results highlight the potential of Chlleaf to reduce the uncertainty of global photosynthesis but identify challenges for incorporating Chlleaf in future terrestrial biosphere models.

Diverse photosynthetic capacity of global ecosystems mapped by satellite chlorophyll fluorescence measurements.

Photosynthetic capacity is often quantified by the Rubisco-limited photosynthetic capacity (i.e. maximum carboxylation rate, Vcmax). It is a key plant functional trait that is widely used in Earth System Models for simulation of the global carbon and water cycles. Measuring Vcmax is time-consuming and laborious; therefore, the spatiotemporal distribution of Vcmax is still poorly understood due to limited measurements of Vcmax. In this study, we used a data assimilation approach to map the spatial variation of Vcmax for global terrestrial ecosystems from a 11-year-long satellite-observed solar-induced chlorophyll fluorescence (SIF) record. In this SIF-derived Vcmax map, the mean Vcmax value for each plant function type (PFT) is found to be comparable to a widely used N-derived Vcmax dataset by Kattge et al. (2009). The gradient of Vcmax along PFTs is clearly revealed even without land cover information as an input. Large seasonal and spatial variations of Vcmax are found within each PFT, especially for diverse crop rotation systems. The distribution of major crop belts, characterized with high Vcmax values, is highlighted in this Vcmax map. Legume plants are characterized with high Vcmax values. This Vcmax map also clearly illustrates the emerging soybean revolution in South America where Vcmax is the highest among the world. The gradient of Vcmax in Amazon is found to follow the transition of soil types with different soil N and P contents. This study suggests that satellite-observed SIF is powerful in deriving the important plant functional trait, i.e. Vcmax, for global climate change studies.

Protective role of glucocorticosteroid prior to endotoxin exposure in cultured neonatal type II alveolar epithelial cells.

BACKGROUND: Dexamethasone (DEX) is widely used for antenatal lung maturation and has been investigated to prevent premature lung injury by inhibiting postnatal inflammation. Its pharmacological mechanisms in the treatment of bacterial infection-induced injury of neonatal lung parenchymal cells remain to be clarified. We hypothesized that DEX pretreatment may attenuate endotoxin-induced growth suppression and regulate cytokine mRNA expression in cultured neonatal type II alveolar epithelial cells (AEC-II). METHODS: AEC-II of newborn piglets were freshly isolated and cultured. After pretreatment of 0.01, 0.1, 1.0 and 10 µmol/l DEX (E0.01, E0.1, E1.0 and E10 group, respectively) for 24 h, the cells were cultured with 1 µg/ml lipopolysaccharides (LPS) for 7 days with medium replacement every 24 h. Messenger RNA expression of surfactant proteins (SPs), pro-inflammatory cytokines and multiple growth factors (GF) were determined by RT-PCR, along with the cell growth and apoptosis measurements. RESULTS: LPS without DEX pretreatment suppressed cell proliferation, enhanced expression of pro-inflammatory cytokine mRNA and apoptosis, which was ameliorated in all DEX-pretreated groups on day 3. On day 3 and 5, only cells pretreated by E1.0 and E10 showed a 20-fold increase in insulin-like GF-1 mRNA expression whereas the expression of other GFs was down-regulated. LPS exposure reduced the expression of SP-A, B, C and Aquaporin-5 mRNA on day 3-7. However, the expression of SP-C mRNA was increased in E1.0 on day 3, which was supported by in situ expression of pro-SP-C with immunocytochemical assay. CONCLUSION: LPS-induced in vitro AEC-II injury was partially prevented by DEX pretreatment, with 1.0 µmol/l being the potentially optimal concentration. (253 words).

Brain-derived neurotrophic factor inhibits calcium channel activation, exocytosis, and endocytosis at a central nerve terminal.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic function and plasticity and plays important roles in neuronal development, survival, and brain disorders. Despite such diverse and important roles, how BDNF, or more generally speaking, neurotrophins affect synapses, particularly nerve terminals, remains unclear. By measuring calcium currents and membrane capacitance during depolarization at a large mammalian central nerve terminal, the rat calyx of Held, we report for the first time that BDNF slows down calcium channel activation, including P/Q-type channels, and inhibits exocytosis induced by brief depolarization or single action potentials, inhibits slow and rapid endocytosis, and inhibits vesicle mobilization to the readily releasable pool. These presynaptic mechanisms may contribute to the important roles of BDNF in regulating synapses and neuronal circuits and suggest that regulation of presynaptic calcium channels, exocytosis, and endocytosis are potential mechanisms by which neurotrophins achieve diverse neuronal functions.

Compound vesicle fusion increases quantal size and potentiates synaptic transmission.

Exocytosis at synapses involves fusion between vesicles and the plasma membrane. Although compound fusion between vesicles was proposed to occur at ribbon-type synapses, whether it exists, how it is mediated, and what role it plays at conventional synapses remain unclear. Here we report the existence of compound fusion, its underlying mechanism, and its role at a nerve terminal containing conventional active zones in rats and mice. We found that high potassium application and high frequency firing induced giant capacitance up-steps, reflecting exocytosis of vesicles larger than regular ones, followed by giant down-steps, reflecting bulk endocytosis. These intense stimuli also induced giant vesicle-like structures, as observed with electron microscopy, and giant miniature excitatory postsynaptic currents (mEPSCs), reflecting more transmitter release. Calcium and its sensor for vesicle fusion, synaptotagmin, were required for these giant events. After high frequency firing, calcium/synaptotagmin-dependent mEPSC size increase was paralleled by calcium/synaptotagmin-dependent post-tetanic potentiation. These results suggest a new route of exocytosis and endocytosis composed of three steps. First, calcium/synaptotagmin mediates compound fusion between vesicles. Second, exocytosis of compound vesicles increases quantal size, which increases synaptic strength and contributes to the generation of post-tetanic potentiation. Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered.