Does the presence of systemic artery-pulmonary circulation shunt during bronchial arterial embolization increase the recurrence of noncancer-related hemoptysis? A retrospective cohort study.

BACKGROUND: The presence of systemic artery-pulmonary circulation shunt (SPS) during the bronchial arterial embolization (BAE) procedure, has been inferred to be a potential risk factor for recurrence. The aim of this study is to reveal the impact of SPS on the recurrence of noncancer-related hemoptysis after BAE. METHODS: In this study, 134 patients with SPS (SPS-present group) and 192 patients without SPS (SPS-absent group) who underwent BAE for noncancer-related hemoptysis from January 2015 to December 2020 were compared. Four different Cox proportional hazards regression models were used to clarify the impact of SPSs on hemoptysis recurrence after BAE. RESULTS: During the median follow-up time of 39.8 months, recurrence occurred in 75 (23.0%) patients, including 51 (38.1%) in the SPS-present group and 24 (12.5%) in the SPS-absent group. The 1-month, 1-year, 2-year, 3-year and 5-year hemoptysis-free survival rates in the SPS-present and SPS-absent groups were 91.8%, 79.7%, 70.6%, 62.3%, and 52.6% and 97.9%, 94.7%, 89.0%, 87.1%, and 82.3%, respectively (P < 0.001). The adjusted hazard ratios of SPSs in the four models were 3.37 [95% confidence intervals (CI), 2.07-5.47, P < 0.001 in model 1], 1.96 (95% CI, 1.11-3.49, P = 0.021 in model 2), 2.29 (95% CI, 1.34-3.92, P = 0.002 in model 3), and 2.39 (95% CI, 1.44-3.97, P = 0.001 in model 4). CONCLUSIONS: The presence of SPS during BAE increases the recurrence probability of noncancer-related hemoptysis after BAE.

Comparison of Bronchial Artery Embolisation Versus Conservative Treatment for Bronchiectasis-Related Nonmassive Haemoptysis: A Single-Centre Retrospective Study.

OBJECTIVE: To compare the safety and effectiveness between bronchial artery embolisation (BAE) and conservative treatment for bronchiectasis-related nonmassive haemoptysis patients. MATERIALS AND METHODS: From January 2015 to December 2020, consecutive bronchiectasis-related nonmassive haemoptysis patients who underwent either BAE (n = 98) or conservative treatment (n = 118) were included. Treatment-related complications, length of hospital stays, clinical success rate, patient satisfaction, and recurrence-free survival rates were compared between groups. Prognostic factors related to recurrence were also analysed. RESULTS: During a median follow-up time of 44.8 months (range, 2.4-83.6 months), 34 and 66 patients in the BAE and conservative treatment groups suffered relapse. The 1-year, 2-year, 3-year and 5-year haemoptysis-free survival rates in the BAE and conservative treatment groups were 79.2%, 68.1%, 62.8%, and 57.6% and 64.0%, 52.8%, 44.1%, and 37.0%, respectively (P = 0.007). The minor complication rate after BAE was higher than that after conservative treatment (23/98 vs. 12/118, P = 0.008). BAE was associated with shorter hospital stays (5.0 vs. 7.0 days, P = 0.042) and higher patient satisfaction (88.8% vs. 74.6%, P = 0.008) than those for conservative treatment and with comparable clinical success rates (95.9% vs. 91.5%, P = 0.192). Treatment type, haemoptysis duration, and bronchiectasis severity were independently significant predictors of recurrence for these patients. CONCLUSIONS: BAE could be another option for bronchiectasis-related nonmassive haemoptysis patients. In the patients with longer duration and more severe bronchiectasis, BAE still appeared to have better long-term haemoptysis control than conservative therapy.

Bronchial artery embolization for the management of frequent hemoptysis caused by bronchiectasis.

BACKGROUND: To retrospectively evaluate the effectiveness of bronchial artery embolization (BAE) compared with conservative therapy for the treatment of frequent hemoptysis caused by bronchiectasis. METHODS: From January 2015 to December 2019, consecutive patients who were admitted due to frequent (more than three times per year) bronchiectasis-related hemoptysis were retrospectively reviewed. Those who were treated with either BAE (n = 69) or conservative therapy (n = 47) were enrolled for analysis. The technical success, clinical success, and complications of the BAE procedure were evaluated. Long-term hemoptysis-free survival rates and clinical success were compared between patients in the BAE group and patients in the conservative group. A Cox proportional hazard regression model was used to identify the predictors of recurrent hemoptysis. RESULTS: The technical success rate was 100% for the BAE procedure, and clinical success was achieved in 92.8% (64 of 69) of cases. No major procedure-related complications occurred, and minor complications were observed in 16 cases (23.2%). The 1-, 2-, and 3-year hemoptysis-free survival rates were 88.3, 71.3, and 66.2%, respectively, for the BAE group and 31.9, 17.6, and 2.5%, respectively, for the conservative treatment group (P <  0.001). Multivariate analysis showed that BAE was a protective factor against recurrent hemoptysis in treated patients. In addition, the presence of cystic bronchiectasis was the only independent risk factor for rebleeding in the whole population and in the BAE group. CONCLUSIONS: BAE may provide an effective option for patients with frequent bronchiectasis-related hemoptysis, especially for those without cystic bronchiectasis.

Low Psoas-Muscle index is associated with decreased survival in hepatocellular carcinoma treated with transarterial chemoembolization.

PURPOSE: Skeletal muscle index (SMI) is a promising predictor of clinical outcomes in patients with malignant diseases. As a simpler surrogate of sarcopenia-psoas muscle index (PMI), its predict value for overall survival (OS) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been reported. To determine if changes in the PMI predicted OS in individuals with HCC treated with TACE. PATIENTS AND METHODS: A retrospective analysis was performed in HCC patients treated with TACE between January 2018 and March 2019. The survival curve according to PMI was estimated by the Kaplan-Meier method and then compared by the log-rank test. Cox proportional hazards models were conducted to identify the prognostic factors for OS. Furthermore, the predictive abilities of PMI and SMI were compared by using Harrell's concordance index (C-index). RESULTS: Two hundred and twenty-eight patients (175 men, mean age 59 ± 11 years) were analysed. The OS was less in patients with low PMI than those with high PMI (median OS: 16.9 vs. 38.5 months, p < .001). Multivariate analysis found that either PMI (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.45-0.91; p < .001) or SMI (HR = 0.51; 95% CI, 0.36-0.72; p < .001) was significantly associated with OS. In the multivariate analysis, the C-index for PMI was 0.78 and 0.79 for SMI (p = .985). CONCLUSION: PMI is a simple tool to predict OS in HCC patients treated with TACE. The predictive ability of PMI is comparable to that of SMI. Key messagesLow psoas-muscle index is associated with decreased overall survival in hepatocellular carcinoma treated with transarterial chemoembolization (TACE).Psoas-muscle index has advantages of being faster and easier to acquire, which thus makes it more likely to achieve widespread clinical application.

Development of a model to predict recurrence after bronchial artery embolization for non-cancer related hemoptysis.

BACKGROUND: Relapse after effective bronchial arterial embolization (BAE) for controlling hemoptysis is not uncommon. Studies reported diverse predictors of recurrence. However, a model to assess the probability of recurrence in non-cancer related hemoptysis patients after BAE has not been reported. This study was to develop a model to predict recurrence after BAE for non-cancer related hemoptysis. METHODS: The study cohort included 487 patients who underwent BAE for non-cancer-related hemoptysis between January 2015 and December 2019. We derived the model's variables from univariate and multivariate Cox regression analyses. The model presented as a nomogram scaled by the proportional regression coefficient of each predictor. Model performance was assessed with respect to discrimination and calibration. RESULTS: One-month and 1-, 2-, 3- and 5-year recurrence-free rates were 94.5%, 88.0%, 81.4%, 76.2% and 73.8%, respectively. Risk factors for recurrence were underlying lung diseases and the presence of systemic arterial-pulmonary circulation shunts. This risk prediction model with two risk factors provided good discrimination (area under curve, 0.69; 95% confidence interval, 0.62-0.76), and lower prediction error (integrated Brier score, 0.143). CONCLUSION: The proposed model based on routinely available clinical and imaging features demonstrates good performance for predicting recurrence of non-cancer-related hemoptysis after BAE. The model may assist clinicians in identifying higher-risk patients to improve the long-term efficacy of BAE.

A Nomogram to Predict Recurrence After Bronchial Artery Embolization for Hemoptysis Due to Bronchiectasis.

OBJECTIVE: To develop and validate a nomogram for predicting recurrent hemoptysis after successful bronchial arterial embolization (BAE) in patients with bronchiectasis. MATERIALS AND METHODS: From January 2015 to December 2019, a total of 251 patients were enrolled in this study. A nomogram was developed with the predictors of recurrent events, which were identified by univariate and multivariate Cox regression analyses. We evaluated nomogram discrimination by area under the receiver operating characteristic curve, calibration by the calibration curve, and clinical usefulness potential by decision curve analysis. RESULTS: The one-month, 1-year, 2-year, 3-year, and 5-year cumulative recurrence-free rates of patients were 98.4%, 90.5%, 82.8%, 77.7%, and 74.4%, respectively. Three predictive factors, namely sex, lung destruction, and systemic arterial-pulmonary circulation shunts, were applied to develop the nomogram. The model maintained good discrimination (area under the curve, 0.72; 95% confidence interval, 0.62-0.81), low prediction error (integrated Brier score, 0.129), and certain net benefits in terms of clinical usefulness. CONCLUSIONS: The proposed nomogram showed favorable predictive efficacy for hemoptysis recurrence after BAE in patients with bronchiectasis. Improved long-term outcomes are expected with close follow-up, a healthy lifestyle, and pulmonary rehabilitation for patients at risk of recurrence according to the model.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Skeletal-muscle index predicts survival after percutaneous transhepatic biliary drainage for obstructive jaundice due to perihilar cholangiocarcinoma.

BACKGROUND: Sarcopenia is emerging as a prognostic factor in patients with malignant diseases. The prognostication of perihilar cholangiocarcinoma (PHC) with obstructive jaundice was complex, because these patients suffered compete mortality events beyond cancer itself. Our study was to investigate the association between low skeletal-muscle index and overall survival (OS) after percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice due to PHC. METHODS: We performed a retrospective survival analysis of patients undergoing PTBD for PHC-related obstructive jaundice between January 2016 and March 2019. Using computed tomography, we measured skeletal-muscle mass at the third lumbar vertebra (L3) to obtain a skeletal-muscle index (SMI). Then, we compared OS between low- and high-SMI groups. Furthermore, factors that could potentially affect OS were assessed. RESULTS: One hundred and four patients (56 males; mean age 66 ± 12 years) were analyzed. Median OS after PTBD was 150 days. OS was shorter in patients with low SMI than in those with high SMI (median OS, 120 vs. 270 days; P < 0.001). Multivariate analysis indicated that low SMI (hazard ratio [HR] 3.46; 95% confidence interval [CI] 1.14-5.60; P < 0.001), intrahepatic metastasis (HR 2.98; 95% CI 1.89-4.69; P < 0.001) and elevated carbohydrate antigen (CA) 19-9 level (HR 1.00; 95% CI 1.00-1.00; P = 0.04) were significantly associated with OS. CONCLUSION: Low SMI was a predictor of dismal OS after PTBD for patients with PHC-related obstructive jaundice.

Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors.

Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene (mcr-1) has rendered polymyxins ineffective. Therefore, the protein encoded by mcr-1, MCR-1, could be a target for structure-based design of inhibitors to tackle polymyxins resistance. Here, we identified racemic compound 3 as a potential MCR-1 inhibitor by virtual screening, and 26 compound 3 derivatives were synthesized and evaluated in vitro. In the cell-based assay, compound 6g, 6h, 6i, 6n, 6p, 6q, and 6r displayed more potent activity than compound 3. Notably, 25 µΜ of compound 6p or 6q combined with 2 µg·mL-1 colistin could completely inhibit the growth of BL21(DE3) expressing mcr-1, which exhibited the most potent activity. In the enzymatic assay, we elucidate that 6p and 6q could target the MCR-1 to inhibit the activity of the protein. Additionally, a molecular docking study showed that 6p and 6q could interact with Glu246 and Thr285 via hydrogen bonds and occupy well the cavity of the MCR-1 protein. These results may provide a potential avenue to overcome colistin resistance, and provide some valuable information for further investigation on MCR-1 inhibitors.

[Effect of Biochar Amendment on Physicochemical Properties and Fungal Community Structures of Cinnamon Soil].

To identify the effect of biochar addition on soil abiotic and biotic properties and provide evidence for the soil improvement with biochar input, the soil physiochemical properties and fungal community were investigated in a cinnamon soil after 3-year biochar additions of 10, 20, and 40 t ·hm-2. The relationship between the fungal community and edaphic physicochemical characteristics was also analyzed. The results showed that soil pH, moisture, total nitrogen (TN), and total organic carbon (TOC) significantly increased but dissolved organic carbon (DOC) content and soil bulk density decreased with biochar addition. High-throughput sequencing results indicated that biochar amendment had little influence on fungal α diversity but significantly changed the fungal community structure. The taxonomic classification showed that the dominant fungal phyla were Ascomycota, Zygomycota, and Basidiomycota, and these phyla accounted for more than 90% of the total sequences. The relative abundance of Ascomycota and Basidiomycota increased, while the abundance of Zygomycota decreased with biochar addition. At the genus level, biochar addition increased the relative abundances of Alternaria, Conocybe, and Aspergillus but decreased the relative abundances of Actinomucor and Gibberella. Redundancy analysis (RDA) showed that soil DOC, pH, and moisture were key environmental factors leading to the shift in the soil fungal community composition. In summary, the application of biochar changed the soil physicochemical properties, which drove the ecological succession of soil fungal communities.

Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels.

INTRODUCTION: Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. METHODS: To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. RESULTS: We found that Sig-1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth-promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca2+ influx and was recapitulated by incubating the neurons with the L-type, N-type, and P/Q-type VGCC blockers, nimodipine, MVIIA and ω-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. CONCLUSION: Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases.

Intersubunit Concerted Cooperative and cis-Type Mechanisms Modulate Allosteric Gating in Two-Pore-Domain Potassium Channel TREK-2.

In response to diverse stimuli, two-pore-domain potassium channel TREK-2 regulates cellular excitability, and hence plays a key role in mediating neuropathic pain, mood disorders and ischemia through. Although more and more input modalities are found to achieve their modulations via acting on the channel, the potential role of subunit interaction in these modulations remains to be explored. In the current study, the deletion (lack of proximal C-terminus, ΔpCt) or point mutation (G312A) was introduced into TREK-2 subunits to limit K(+) conductance and used to report subunit stoichiometry. The constructs were then combined with wild type (WT) subunit to produce concatenated dimers with defined composition, and the gating kinetics of these channels to 2-Aminoethoxydiphenyl borate (2-APB) and extracellular pH (pHo) were characterized. Our results show that combination of WT and ΔpCt/G312A subunits reserves similar gating properties to that of WT dimmers, suggesting that the WT subunit exerts dominant and positive effects on the mutated one, and thus the two subunits controls channel gating via a concerted cooperative manner. Further introduction of ΔpCt into the latter subunit of heterodimeric channel G312A-WT or G312A-G312A attenuated their sensitivity to 2-APB and pHo alkalization, implicating that these signals were transduced by a cis-type mechanism. Together, our findings elucidate the mechanisms for how the two subunits control the pore gating of TREK-2, in which both intersubunit concerted cooperative and cis-type manners modulate the allosteric regulations induced by 2-APB and pHo alkalization.

Allosteric coupling between proximal C-terminus and selectivity filter is facilitated by the movement of transmembrane segment 4 in TREK-2 channel.

TREK-2, a member of two-pore-domain potassium channel family, regulates cellular excitability in response to diverse stimuli. However, how such stimuli control channel function remains unclear. Here, by characterizing the responses of cytosolic proximal C-terminus deletant (ΔpCt) and transmembrane segment 4 (M4)-glycine hinge mutant (G312A) to 2-Aminoethoxydiphenyl borate (2-APB), an activator of TREK-2, we show that the transduction initiated from pCt domain is allosterically coupled with the conformation of selectivity filter (SF) via the movements of M4, without depending on the original status of SF. Moreover, ΔpCt and G312A also exhibited blunted responses to extracellular alkalization, a model to induce SF conformational transition. These results suggest that the coupling between pCt domain and SF is bidirectional, and M4 movements are involved in both processes. Further mechanistic exploration reveals that the function of Phe316, a residue close to the C-terminus of M4, is associated with such communications. However, unlike TREK-2, M4-hinge of TREK-1 only controls the transmission from pCt to SF, rather than SF conformational changes triggered by pHo changes. Together, our findings uncover the unique gating properties of TREK-2, and elucidate the mechanisms for how the extracellular and intracellular stimuli harness the pore gating allosterically.

Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes.

Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively in nociceptive primary sensory neurons and the neurons located in stratum granulosum of skin. More and more evidence suggest that MrgD plays an important role in pain sensation and/or transduction. Recent studies have demonstrated that the receptor is also involved in itch sensation in both mouse and human. In the present study, we identified a robust inward current in MrgD-expressing Xenopus oocytes by using ß-alanine, a putative ligand of MrgD. The currents were sensitive to inhibitor of Ca(2+)-activated chloride channels (CaCCs) and intracellular Ca(2+) chelator, suggesting they were produced by endogenous CaCCs. Furthermore, it was demonstrated that upon the application of phospholipase C (PLC) inhibitor, or antisense oligonucleotides of inositol trisphosphate receptor (IP3R), the ß-alanine-induced currents were dramatically depressed. However, protein kinase C inhibitor did not display any visible effect on CaCC currents. In summary, our data suggest that the activation of MrgD promotes the open of endogenous CaCCs via G(q)-PLC-IP3-Ca(2+) pathway. The current findings reveal the functional coupling between MrgD and CaCCs in Xenopus oocytes and also provide a facile model to assay the activity of MrgD.

Aquaporin-4 deficiency attenuates opioid dependence through suppressing glutamate transporter-1 down-regulation and maintaining glutamate homeostasis.

BACKGROUND: Glutamate homeostasis plays a critical role in mediating the addiction-related behaviors. Therefore, preventing the disruption or reestablishing of it is a novel strategy for the treatment of addiction. Glutamate transporters are responsible for clearing extracellular glutamate and maintaining glutamate homeostasis. Our previous work demonstrated that aquaporin-4 (AQP4) deficiency attenuated morphine dependence, but the mechanisms are unclear. According to the recent evidence that AQP4 might form a functional complex with glutamate transporter-1 (GLT-1), this study focused on whether AQP4 participates in the modulation of GLT-1 and glutamate homeostasis in morphine-dependent mice. RESULTS: We found that AQP4 knockout prevented the down-regulations of GLT-1 expression and glutamate clearance when mice were repeatedly treated with morphine. Further study revealed that inhibition of GLT-1 by dihydrokainic acid (DHK) initiated morphine dependence in AQP4 knockout mice. In addition, AQP4 knockout abolished both decreases and increases in the extracellular glutamate levels in the prefrontal cortex during repeated morphine treatment and naloxone-precipitated withdrawal. CONCLUSION: AQP4 deficiency suppresses the down-regulation of GLT-1, and the disruption of glutamate homeostasis caused by repeated exposure to morphine, pointing to a strategy for maintaining glutamate homeostasis and thereby treating addiction through the modulation of AQP4 function and expression.

External Ba2+ block of the two-pore domain potassium channel TREK-1 defines conformational transition in its selectivity filter.

TREK-1 is a member of the two-pore domain potassium channel family that is known as a leak channel and plays a key role in many physiological and pathological processes. The conformational transition of the selectivity filter is considered as an effective strategy for potassium channels to control the course of potassium efflux. It is well known that TREK-1 is regulated by a large volume of extracellular and intracellular signals. However, until now, little was known about the selectivity filter gating mechanism of the channel. In this research, it was found that Ba(2+) blocked the TREK-1 channel in a concentration- and time-dependent manner. A mutagenesis analysis showed that overlapped binding of Ba(2+) at the assumed K(+) binding site 4 (S4) within the selectivity filter was responsible for the inhibitory effects on TREK-1. Then, Ba(2+) was used as a probe to explore the conformational transition in the selectivity filter of the channel. It was confirmed that collapsed conformations were induced by extracellular K(+)-free and acidification at the selectivity filters, leading to nonconductive to permeable ions. Further detailed characterization demonstrated that the two conformations presented different properties. Additionally, the N-terminal truncated isoform (ΔN41), a product derived from alternative translation initiation, was identified as a constitutively nonconductive variant. Together, these results illustrate the important role of selectivity filter gating in the regulation of TREK-1 by the extracellular K(+) and proton.

[Research on clouds affecting the spectra of solar ultraviolet radiation].

In the present paper, using UV CCD optical multi-channel analyzer, the solar ultraviolet radiation spectra under the conditions of cloud cover were measured, and the impact of clouds on the solar ultraviolet radiation spectra were studied mostly. The results of spectral analysis showed that the intensity of solar ultraviolet radiation spectra was weakened by the clouds. The solar ultraviolet radiation spectral intensity attenuation depended on the wavelength and decreased with decreasing wavelength. The greater the cloud cover, the stronger the attenuation, The solar ultraviolet radiation spectral intensity at wavelengths below 315 nm was affected relatively less by the cloud cover. These results have more important practical applications. When we use solar ultraviolet radiation spectrum to study the atmospheric composition, we should choose the spectral band that is less affected by the atmospheric environment.

Involvement of tissue transglutaminase in endothelin 1-induced hypertrophy in cultured neonatal rat cardiomyocytes.

A potential link between tissue-type transglutaminase (tTG) and cardiac hypertrophy was suggested recently. However, whether tTG is implicated in hypertrophic agonist-induced cardiac hypertrophy is not yet known. The purpose of this study was to investigate the effects of tTG on cardiomyocyte hypertrophy induced by endothelin (ET) 1. Real-time quantitative RT-PCR and Western blot analysis demonstrated that ET-1 increased the expression of tTG mRNA and protein in cardiomyocytes by activating ET(A) receptors. ET-1 failed to cause increases in cell size and [(3)H]leucine uptake, sarcomere reorganization, and gene induction of the atrial natriuretic factor when cardiomyocytes were treated with monodansylcadaverine, a competitive inhibitor of tTG. Furthermore, the effects of ET-1 on multifunctional activities of tTG were determined by evaluating the incorporation of [(3)H]putrescine into N,N'-dimethylated casein and charcoal absorption, respectively. The results showed that ET-1 did not influence the basal transglutaminase activity of cardiomyocytes but significantly inhibited the 0.1-mmol/L Ca(2+)-stimulated transglutaminase activity. Otherwise, ET-1 elevated the activity of GTPase in a concentration- and time-dependent manner. In vivo, right ventricular hypertrophy induced by 2 weeks of chronic hypoxia was depressed by the tTG inhibitor cystamine (10 to 30 mg/kg, 2 times per day, IP) in a dose-dependent manner. Taken together, our data strongly supported the notion that tTG may act as a positive regulator of the hypertrophic program in response to ET-1. This is probably attributable to the signaling activity of tTG rather than transglutaminase activity.

Effects of aquaporin4 deficiency on opioid receptors characteristics in naive and chronic morphine-treated mice.

Our previous study indicated that aquaporin4 (AQP4) deficiency potentiated morphine analgesia, but attenuated tolerance and physical dependence induced by chronic exposure to morphine. However, the mechanisms remained to be explored. In the present study, effects of AQP4 deficiency on opioid receptor characteristics were investigated by [(3)H]-diprenorphine binding assays. In basal condition, the K(d) values of opioid receptors increased from 0.27+/-0.03 nM in wild-type mice to 0.44+/-0.04 nM in AQP4 deficient mice. Meanwhile, the density (B(max) values) of opioid receptors increased from 0.40+/-0.04 pmol/mg protein in wild-type mice to 0.66+/-0.04 pmol/mg protein in AQP4 deficient mice. After chronic morphine treatment, the affinity of opioid receptors decreased in wild-type mice, in which the K(d) value increased from 0.27+/-0.03 nM to 0.40+/-0.04 nM, while no change in the density of opioid receptors was observed. In AQP4 knockout mice, the effects of chronic morphine treatment on opioid receptors were similar to that in wild-type mice, in which the K(d) values increased from 0.44+/-0.04 nM to 0.64+/-0.08 nM, whereas the density had no significant change. Taken together, at the first time, we found that AQP4 deficiency decreased the affinity and increased the density of opioid receptors. Additionally, AQP4 deficiency did not affect chronic morphine-induced alterations of opioid receptor characteristics.

Aquaporin 4 deficiency modulates morphine pharmacological actions.

Acute administration of opioids produces analgesia, while chronic administration induces tolerance and dependence. Aquaporin 4 (AQP4) is most strongly expressed in astrocytes throughout central nervous system, and plays an important role in some pathophysiological processes in brain. However, whether AQP4 modulates opioid analgesia, tolerance and dependence or not remains unknown. In the present study, the effects of AQP4 deficiency on morphine analgesia, tolerance and physical dependence were investigated. (1) In hot-plate tests, ED(50) values of morphine analgesia were 3.77 and 3.96 mg/kg in male and female AQP4 knockout mice, which were lower than that in wild-type mice (5.23 and 5.20mg/kg in males and females). (2) Repeated treatment with morphine resulted in analgesic tolerance to morphine in wild-type mice, whereas the morphine tolerance was attenuated in AQP4 knockout mice treated as the same schedule. (3) After repeated morphine administration, naloxone precipitation induced significant abstinent jumping in wild-type mice, whereas naloxone-induced abstinent jumping was not observed in AQP4 knockout mice. This suggested that AQP4 deficiency inhibited the development of morphine physical dependence. (4) Repeated morphine administration down-regulated cerebral glutamate transporter 1 (GLT-1) expression in wild-type mice. However, the down-regulation of GLT-1 expression diminished in AQP4 knockout mice. Taken together, these results demonstrated that AQP4 deficiency potentiated morphine analgesia, attenuated morphine tolerance and physical dependence. The suppression of down-regulation of cerebral GLT1 expression might mediate the attenuation of AQP4 deficiency to morphine tolerance and dependence.