Dynamics and regulatory role of circRNAs in Asian honey bee larvae following fungal infection.

Non-coding RNA (ncRNA) plays a vital part in the regulation of immune responses, growth, and development in plants and animals. Here, the identification, characteristic analysis, and molecular verification of circRNAs in Apis cerana cerana worker larval guts were conducted, followed by in-depth investigation of the expression pattern of larval circRNAs during Ascosphaera apis infection and exploration of the potential regulatory part of differentially expressed circRNAs (DEcircRNAs) in host immune responses. A total of 3178 circRNAs in the larval guts of A. c. cerana were identified, with a length distribution ranging from 15 to 96,007 nt. Additionally, 155, 95, and 86 DEcircRNAs were identified in the in the 4-, 5-, and 6-day-old larval guts following A. apis infection. These DEcircRNAs were predicted to target 29, 25, and 18 parental genes relevant to 12, 20, and 17 GO terms as well as 144, 114, and 61 KEGG pathways, including 5 cellular and 4 humoral immune pathways. Complex competing endogenous RNA (ceRNA) regulatory networks were detected as being formed among DEcircRNAs, DEmiRNAs, and DEmRNAs. The target DEmRNAs were engaged in 36, 47, and 47 GO terms as well as 331, 332, and 331 pathways, including 6 cellular and 6 humoral immune pathways. Further, 19 DEcircRNAs, 5 DEmiRNAs, and 3 mRNAs were included in the sub-networks relative to 3 antioxidant enzymes. Finally, back-splicing sites within 15 circRNAs and the difference in the 15 DEcircRNAs' expression between uninoculated and A. apis-inoculated larval guts were confirmed based on molecular methods. These findings not only enrich our understanding of bee host-fungal pathogen interactions but also lay a foundation for illuminating the mechanism underlying the DEcircRNA-mediated immune defense of A. c. cerana larvae against A. apis invasion. KEY POINTS: • The expression pattern of circRNAs was altered in the A. cerana worker larval guts following A. apis infection. • Back-splicing sites within 15 A. cerana circRNAs were verified using molecular approaches. DEcircRNAs potentially modulated immune responses and antioxidant enzymes in A. apis-challenged host guts.

Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study.

BACKGROUND: The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI. METHODS: Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan-Meier survival methods. RESULTS: In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23-14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197-4.263) and 2.167 (1.157-4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161-6.450) and 3.272 (1.408-7.607), respectively (both p < 0.05). CONCLUSIONS: Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.

Predictive efficacy of neutrophil-to-lymphocyte ratio for long-term prognosis in new onset acute coronary syndrome: a retrospective cohort study.

BACKGROUND: Inflammation is involved in the pathogenesis and progression of coronary artery diseases (CADs), including acute coronary syndrome. The neutrophil-to-lymphocyte ratio (NLR) has been identified as a novel marker of the pro-inflammatory state. We aimed to evaluate the predictive efficacy of the NLR for the prognosis of patients with new-onset ACS. METHODS: We retrospectively included consecutive patients with new-onset ACS treated with emergency coronary angiography. NLR was measured at baseline and analyzed by tertiles. The severity of coronary lesions was evaluated by the Gensini score. Correlations of NLR with the severity of CAD and the incidence of major adverse cardiovascular diseases (MACEs) during follow-up were determined. RESULTS: Overall, 737 patients were included. The NLR was positively correlated with the severity of coronary lesions as assessed by Gensini score (P < 0.05). During the follow-up period (mean, 43.49 ± 23.97 months), 65 MACEs occurred. No significant association was detected between baseline NLR and the risk of MACEs during follow-up by either Kaplan-Meier or Cox regression analysis. Multivariable logistic regression analysis showed that a higher NLR was independently associated with coronary lesion severity as measured by the Gensini score (1st tertile vs. 3rd tertile hazard ratio [HR]: 0.527, P < 0.001, and 2nd tertile vs. 3rd tertile HR: 0.474, P = 0.025). CONCLUSIONS: The NLR may be associated with coronary disease severity at baseline but is not associated with adverse outcomes in patients with new-onset ACS. ETHICS APPROVAL NUMBER: 2019XE0208.

Steroids from the seeds of Datura metel.

Two new steroids meteloside F (1) and meteloside G (2), together with six known ones (3-8), were isolated and identified from the seeds of Datura metel L. The chemical constituents were isolated by silica gel, ODS chromatogram columns. and preparative HPLC. The structures of these compounds were established by one- and two-dimensional NMR spectra and HR-ESI-MS. The compounds exhibited inhibition on the nitric oxide release of lipopolysaccharide-induced RAW 264.7 cells with IC50 values from 30.2 to 44.8 µM. [Formula: see text].

Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role.

New Glycosides from the Fruits of Nicandra physaloides.

Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values from 26.9 to 47.5 µM.

TIG3 interaction at the centrosome alters microtubule distribution and centrosome function.

TIG3 is an important pro-differentiation regulator that is expressed in the suprabasal epidermis. We have shown that TIG3 activates selective keratinocyte differentiation-associated processes leading to cornified envelope formation. However, TIG3 also suppresses cell proliferation by an unknown mechanism. Our present studies suggest that cessation of growth is mediated through the impact of TIG3 on the centrosome and microtubules. The centrosome regulates microtubule function in interphase cells and microtubule spindle formation in mitotic cells. We show that TIG3 colocalizes with γ-tubulin and pericentrin at the centrosome. Localization of TIG3 at the centrosome alters microtubule nucleation and reduces anterograde microtubule growth, increases acetylation and detyrosination of α-tubulin, increases insoluble tubulin and drives the formation of a peripheral microtubule ring adjacent to the plasma membrane. In addition, TIG3 suppresses centrosome separation, but not duplication, and reduces cell proliferation. We propose that TIG3 regulates the formation of the peripheral microtubule ring observed in keratinocytes of differentiated epidermis and also has a role in the cessation of proliferation in these cells.

Multimodal Data Integration Enhance Longitudinal Prediction of New-Onset Systemic Arterial Hypertension Patients with Suspected Obstructive Sleep Apnea.

Background: It is crucial to accurately predict the disease progression of systemic arterial hypertension in order to determine the most effective therapeutic strategy. To achieve this, we have employed a multimodal data-integration approach to predict the longitudinal progression of new-onset systemic arterial hypertension patients with suspected obstructive sleep apnea (OSA) at the individual level. Methods: We developed and validated a predictive nomogram model that utilizes multimodal data, consisting of clinical features, laboratory tests, and sleep monitoring data. We assessed the probabilities of major adverse cardiac and cerebrovascular events (MACCEs) as scores for participants in longitudinal cohorts who have systemic arterial hypertension and suspected OSA. In this cohort study, MACCEs were considered as a composite of cardiac mortality, acute coronary syndrome and nonfatal stroke. The least absolute shrinkage and selection operator (LASSO) regression and multiple Cox regression analyses were performed to identify independent risk factors for MACCEs among these patients. Results: 448 patients were randomly assigned to the training cohort while 189 were assigned to the verification cohort. Four clinical variables were enrolled in the constructed nomogram: age, diabetes mellitus, triglyceride, and apnea-hypopnea index (AHI). This model accurately predicted 2-year and 3-year MACCEs, achieving an impressive area under the receiver operating characteristic (ROC) curve of 0.885 and 0.784 in the training cohort, respectively. In the verification cohort, the performance of the nomogram model had good discriminatory power, with an area under the ROC curve of 0.847 and 0.729 for 2-year and 3-year MACCEs, respectively. The correlation between predicted and actual observed MACCEs was high, provided by a calibration plot, for training and verification cohorts. Conclusions: Our study yielded risk stratification for systemic arterial hypertension patients with suspected OSA, which can be quantified through the integration of multimodal data, thus highlighting OSA as a spectrum of disease. This prediction nomogram could be instrumental in defining the disease state and long-term clinical outcomes.

Development and preclinical evaluation of a biodegradable ventricular septal defect occluder.

OBJECTIVES: This study evaluated the feasibility, effectiveness, and safety of a biodegradable (BD) occluder for closure of ventricular septal defect (VSD) in an acute canine model. BACKGROUND: All current available VSD occluders are permanent implants which consist of a metal framework and synthetic fabrics. However, the septal occluder in vivo plays the role of a temporary bridge that facilitates the ingrowth of fibrous connective tissue and endothelialization. The ideal occluder may be a temporary scaffold which can be gradually absorbed in vivo and replaced by "native" tissue. METHODS: The BD VSD occluder consists of a polydioxanone (PDO) framework and two pieces of poly-L-lactic acid (PLLA) fabrics. Percutaneous transcatheter closure of interventionally created VSDs was performed in 16 dogs using the BD occluders. Follow-up consisted of electrocardiography, transthoracic echocardiography, and fluoroscopy from 1 week to 24 weeks post-implantation. Gross pathology and histopathology were obtained at 6, 12, and 24 weeks follow-up. RESULTS: Implantation of the BD occluders was successful in 15 animals. The devices became well integrated into the ventricular septum with complete endothelialization at 12 weeks after implantation. After 24 weeks in vivo, the PDO framework of devices was largely absorbed and replaced by the ingrowth of collagenous fibers, and the PLLA fabric within disks was partly degraded. Neither occluder dislocation nor VSD recanalization occurred during follow-up. CONCLUSIONS: The BD occluder proved safe and effective for VSD closure. This device is characterized by compatible mechanical properties, a fully BD property, and a good match between the degradation of occluder and the healing response of organism.

Ag2NCN anchored on Ti3C2Tx MXene as a Schottky heterojunction: enhanced visible light photocatalytic efficiency of rhodamine B degradation.

The quick charge recombination of light-generated electrons and holes severely restricts the photocatalytic applications of single semiconductors. Here, a straightforward electrostatically driven self-assembly technique was used to construct an Ag2NCN/Ti3C2Tx Schottky heterojunction, which was then used to degrade Rhodamine B (RhB) in the illumination of visible light. The findings from the experiments revealed that as a cocatalyst, Ti3C2Tx significantly suppresses the recombination rate and broadens visible absorptivity to improve Ag2NCN photocatalytic efficiency. The optimized Ag2NCN/Ti3C2Tx (AT2) composite exhibited an outstanding photocatalytic rate in 96 min, with the highest RhB degradation rate (k = 0.029 min-1), which was around fifteen times that of pure Ag2NCN (k = 0.002 min-1). Furthermore, the trapping-agent experiment showed photogenerated superoxide radicals and holes were the principal active agents inside the photodegradation of RhB. Compared with Ag-based semiconductors, the composite exhibited outstanding photostability, highlighting its excellent potential for application in visible-light photocatalysis.

Study on the Preparation and Optical Properties of Graphene Oxide@Fe3O4 Two-Dimensional Magnetically Oriented Nanocomposites.

In this work, graphene oxide@Fe3O4 (GO@Fe3O4) two-dimensional magnetically oriented nanocomposites were prepared through the co-precipitation approach using graphene oxide as the carrier and FeCl3·6H2O and FeSO4·7H2O as iron sources. The samples were characterized and tested by X-ray diffraction, a transmission electron microscope, Fourier-transform infrared spectroscopy, a vibrating-specimen magnetometer, a polarized optical microscope, an optical microscope, etc. The effects of material ratios and reaction conditions on the coating effects of Fe3O4 on the GO surface were investigated. The stable GO@Fe3O4 sol system was studied and constructed, and the optical properties of the GO@Fe3O4 sol were revealed. The results demonstrated the GO@Fe3O4 two-dimensional nanocomposites uniformly coated with Fe3O4 nanoparticles were successfully prepared. The GO@Fe3O4 two-dimensional nanocomposites exhibited superparamagnetic properties at room temperature, whose coercive force was 0. The stable GO@Fe3O4 sol system could be obtained by maintaining 1 < pH < 1.5. The GO@Fe3O4 sol showed magneto-orientation properties, liquid crystalline properties, and photonic crystal properties under the influence of the external magnetic field. The strength and direction of the magnetic field and the solid content of the GO@ Fe3O4 sol could regulate the aforementioned properties. The results suggest that GO@Fe3O4 two-dimensional magnetically oriented nanocomposites have potential applications in photonic switches, gas barriers, and display devices.

Nano-sized aggregate Ti3C2-TiO2 supported on the surface of Ag2NCN as a Z-scheme catalyst with enhanced visible light photocatalytic performance.

Exposing the photocatalyst's highly active facets and hybridizing the photocatalyst with suitable cocatalysts in the proper spot have been recognized as strong methods for high-performance photocatalysts. Herein, Ag2NCN/TiO2-Ti3C2 composites were synthesized by applying simple calcination and physically weak interaction deposition processes to obtain an excellent photocatalyst for Rhodamine B (Rh B) degradation when exposed to visible light. The findings from the experiments reveal that the Ag2NCN/TiO2-Ti3C2400 composite exhibited an outstanding photocatalytic rate in 80 min, with the highest Rh B degradation rate (k = 0.03889 min-1), which was 16 times higher than that of pure Ag2NCN (k = 0.00235 min-1) and 2.2 times higher than that of TiO2-Ti3C2400 (k = 0.01761 min-1). The results from the following factors: (i) the powerful interfacial contact created by the in situ formation of TiO2, and the superior electrical conductivity of Ti3C2 that makes carrier separation possible; (ii) TiO2 with electron-rich (101) facets are deposited on the surface of Ag2NCN, significantly reducing charge carrier recombination by trapping photoelectrons; (iii) a Z-type heterojunction is constructed between nanosize aggregate Ti3C2-TiO2 and Ag2NCN with non-metal Ti3C2 as the solid medium, improving the transfer and separation of photogenerated charges and inhibiting the recombination of electrons and holes. Additionally, the redox ability of the composite photocatalyst is enhanced. Furthermore, the analyses of active species showed that photogenerated superoxide radicals and holes were the principal active agents inside the photodegradation of Rh B. Moreover, the composite exhibited outstanding photo-stability.

Phenolic glycosides and indole alkaloids isolated from the roots and rhizomes of Clematis chinensis and their anti-inflammatory activity.

Six undescribed compounds, including three phenolic glycosides (1-3) and three indole alkaloids (4-6), together with ten known alkaloids (7-16) and three known phenolic glycosides (17-19), were isolated from 70% EtOH aqueous extracts of the roots and rhizomes of Clematis chinensis Osbeck. The structures were elucidated by NMR, HRESIMS and X-ray diffraction spectroscopies. The anti-inflammatory activity of these compounds was evaluated, and twelve compounds showed significant inhibitory activity against TNF-α with an inhibition ratio from 47.87% to 94.70% at a dose of 10 µM. Compound 7 exhibited significant inhibitory activity against TNF-α and IL-6 with IC50 values of 3.99 µM and 2.24 µM, respectively. Compound 8 displayed potent anti-inflammatory activity against mouse ear edema induced by croton oil. A mechanistic study suggested that compounds 7 and 8 decreased the activation of the NF-κB signaling pathway to reduce the secretion of inflammatory factors in LPS-induced RAW 264.7 cells.

Animal experimental study of the fully biodegradable atrial septal defect (ASD) occluder.

This study was conducted to evaluate the feasibility, safety, biocompatibility, and degradation features of a fully biodegradable occluder for closure of atrial septal defect (ASD) in an acute canine model. The ASD was created in 20 healthy mongrel dogs by the brockenbrough needle, and the fully biodegradable occluders were implanted by self-made delivery system. The success rate and complications were observed. Acute ASD models were successfully created in 18 dogs, and 16 occluders were successfully implanted in the ASD models. Animals were sacrificed at different times after procedure. The cardiac gross anatomy showed that all occluders were stable in the interatrial septum, no vegetation or thrombus formation was observed on the surface of all occluders. They were embedded into endogenous host tissue gradually at 12-week follow-up. Different periods of pathological observations suggested that the occluders degraded gradually over about 24 weeks and essentially became an integral part of the septum. Transcatheter closure of ASD in acute canine model using the fully biodegradable ASD occluder has the potential of a high successful rate of technique, excellent biocompatibility, and fewer complications with adequate, immediate, and short-term results.

CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity.

Mutation in leucine-rich repeat kinase-2 (LRRK2) is the most common cause of late-onset Parkinson's disease (PD). Although most cases of PD are sporadic, some are inherited, including those caused by LRRK2 mutations. Because these mutations may be associated with a toxic gain of function, controlling the expression of LRRK2 may decrease its cytotoxicity. Here we show that the carboxyl terminus of HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes the ubiquitin proteasomal degradation of LRRK2. Overexpression of CHIP protects against and knockdown of CHIP exacerbates toxicity mediated by mutant LRRK2. Moreover, HSP90 forms a complex with LRRK2, and inhibition of HSP90 chaperone activity by 17AAG leads to proteasomal degradation of LRRK2, resulting in increased cell viability. Thus, increasing CHIP E3 ligase activity and blocking HSP90 chaperone activity can prevent the deleterious effects of LRRK2. These findings point to potential treatment options for LRRK2-associated PD.

Long Noncoding RNA AF131217.1 Regulated Coronary Slow Flow-Induced Inflammation Affecting Coronary Slow Flow via KLF4.

INTRODUCTION: This study investigated the correlation between the levels of long noncoding ribonucleic acids (lncRNAs) AF131217.1 and coronary slow flow (CSF). METHODS: A total of 22 patients in the high-sensitivity C-reactive protein (hsCRP) group diagnosed with CSF from January 2018 to December 2018 were enrolled in this study. Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) method. Results: LncRNA AF131217.1 expression in the CSF model was activated. Mean TFC was positively correlated with lncRNA AF131217.1 levels and hsCRP levels. LncRNA AF131217.1 induced inflammation factor levels in the in vitro model. Micro ribonucleic acid (miR)-128-3p is a target spot of lncRNA AF131217.1 on the inflammation in vitro model via Kruppel-like factor (KLF) 4. MiR-128-3p reduced inflammation factor levels (tumor necrosis factor alpha, interleukin [IL]-6, IL-1ß, and IL-18). Conclusion: Thus, lncRNA AF131217.1 promoted inflammation in the regulated CSF via KLF4 by miR-128-3p.

New permanent bundle-branch block and long-term prognosis of patients with new onset ST-elevation myocardial infarction who underwent percutaneous coronary intervention.

Aim: The aim of the study was to evaluate the potential predictive value of permanent RBBB and LBBB for longer-term prognosis in patients with new-onset STEMI who underwent percutaneous coronary intervention (PCI). Methods: Patients with new-onset STEMI that underwent emergency PCI at our department from June 2012 to September 2020 were included in the study. Gensini score (GS) was employed to evaluate the severity of coronary lesions. The primary endpoint of the study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), the composite of cardiac mortality, recurrence of myocardial infarction, cardiac shock, stroke, stent thrombosis, or revascularization. We also set all-cause mortality as a secondary endpoint. Results: Out of the 547 patients, 29 patients had new-onset permanent LBBB, 51 patients had new-onset permanent RBBB, and 467 patients had no bundle-branch block (BBB). The occurrence of no BBB, new permanent LBBB, or RBBB was not associated with the severity of coronary artery lesions as evaluated by the GS. After follow-up at an average of 43.93 months, MACCEs occurred in 52 patients. Kaplan-Meier analysis showed that patients with new-onset RBBB were at greater risk for MACCEs compared to those with new onset LBBB (χ2 = 5.107, p = 0.021). Also, an independent correlation was found between new permanent RBBB and LBBB and MACCEs risk. The adjusted hazard ratios (HRs) were 6.862 [95% confidence interval (CI) of 3.764-12.510] for the new-onset permanent RBBB and 3.395 (95% CI of 1.280-9.005) for LBBB, compared to those with no BBB, respectively (both p < 0.05). Conclusion: New onset permanent RBBB in patients with new onset STEMI who underwent PCI may be correlated independently with increased risk of poor long-term prognosis.

Type I transglutaminase accumulation in the endoplasmic reticulum may be an underlying cause of autosomal recessive congenital ichthyosis.

Type I transglutaminase (TG1) is an enzyme that is responsible for assembly of the keratinocyte cornified envelope. Although TG1 mutation is an underlying cause of autosomal recessive congenital ichthyosis, a debilitating skin disease, the pathogenic mechanism is not completely understood. In the present study we show that TG1 is an endoplasmic reticulum (ER) membrane-associated protein that is trafficked through the ER for ultimate delivery to the plasma membrane. Mutation severely attenuates this processing and a catalytically inactive point mutant, TG1-FLAG(C377A), accumulates in the endoplasmic reticulum and in aggresome-like structures where it is ubiquitinylated. This accumulation results from protein misfolding, as treatment with a chemical chaperone permits it to exit the endoplasmic reticulum and travel to the plasma membrane. ER accumulation is also observed for ichthyosis-associated TG1 mutants. Our findings suggest that misfolding of TG1 mutants leads to ubiquitinylation and accumulation in the ER and aggresomes, and that abnormal intracellular processing of TG1 mutants may be an underlying cause of ichthyosis.

Percutaneous valved stent implantation above the coronary ostia.

BACKGROUND: In recent years, some experimental and clinical studies on transcatheter aortic valve implantation (TAVI) have been conducted. TAVI is indicated in patients with calcified pure or predominant aortic stenosis. The risk of this technique is still high. Aortic valved stent implantation above the coronary ostia might avoid blocking the coronary ostia. METHODS AND RESULTS: Twenty healthy dogs were selected to establish a canine model of acute aortic valve rupture. The dogs were randomly divided into 2 groups: the rupture model group without any treatment and the valved stent group with percutaneous valved stent implantation above the coronary ostia. The 2 groups of animals were followed up for 3 months. Echocardiography and other tests were performed to assess aortic regurgitation and ventricular function. Acute aortic valve rupture models were successfully established in 16 of 20 dogs. In the rupture model group, the mean aortic regurgitation was 6.8 ± 1.9 ml/s; only 3 of 8 animals survived for 3 months. In the valved stent group, the mean aortic regurgitation was 7.0 ± 2.1 ml/s; valved stents were successfully implanted in 8 animals. Instant post-implantation anatomy showed that the stents were located appropriately. Seven dogs survived for 3 months. CONCLUSIONS: Percutaneous valved stent implantation above the coronary ostia is feasible and effective as a transitional treatment for acute aortic valve rupture.

A Drosophila model for LRRK2-linked parkinsonism.

Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo"gain-of-function" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention.