Optimizing Post-Acute Coronary Syndrome Dyslipidemia Management: Insights from the North American Acute Coronary Syndrome Reflective III.

INTRODUCTION: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. METHODS: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1-12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. RESULTS: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3-12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3-6 months] to 1.87 mmol/L [6-12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3-6 months] to 53.4% [6-12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. CONCLUSION: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium-pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

EARLY BUD BREAK 1 triggers bud break in peach trees by regulating hormone metabolism, the cell cycle, and cell wall modifications.

In a previous study we identified EARLY BUD BREAK 1 (EBB1), an ERF transcription factor, in peach (Prunus persica var. nectarina cultivar Zhongyou 4); however, little is known of how PpEBB1 may regulate bud break. To verify the function of PpEBB1 in bud break, PpEBB1 was transiently transformed into peach buds, resulting in early bud break. Bud break occurred earlier in PpEBB1-oe poplar (Populus trichocarpa) obtained by heterologous transformation than in wild type (WT), consistent with the peach bud results, indicating that PpEBB1 can promote bud break. To explore how PpEBB1 affects bud break, differentially expressed genes (DEGs) between WT and PpEBB1-oe poplar plants were identified by RNA-sequencing. The expression of DEGs associated with hormone metabolism, cell cycle, and cell wall modifications changed substantially according to qRT-PCR. Auxin, ABA, and total trans-zeatin-type cytokinin levels were higher in the PpEBB1-oe plants than in WT plants, while the total N6-(Δ 2-isopentenyl)-adenine-type cytokinins was lower. Yeast two-hybrid and bimolecular fluorescence complementation assays verified that a cell wall modification-related protein (PpEXBL1) interacted with PpEBB1 suggesting that PpEBB1 could interact with these cell wall modification proteins directly. Overall, our study proposed a multifaceted explanation for how PpEBB1 regulates bud break and showed that PpEBB1 promotes bud break by regulating hormone metabolism, the cell cycle, and cell wall modifications.

Transcription factor TCP20 regulates peach bud endodormancy by inhibiting DAM5/DAM6 and interacting with ABF2.

The dormancy-associated MADS-box (DAM) genes PpDAM5 and PpDAM6 have been shown to play important roles in bud endodormancy; however, their molecular regulatory mechanism in peach is unclear. In this study, by use of yeast one-hybrid screening, we isolated a TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR transcription factor, PpTCP20, in the peach cultivar 'Zhongyou 4' (Prunus persica var. nectarina). The protein was localized in the nucleus and was capable of forming a homodimer. Electrophoretic mobility shift assays demonstrated that PpTCP20 binds to a GCCCR element in the promoters of PpDAM5 and PpDAM6, and transient dual luciferase experiments showed that PpTCP20 inhibited the expression of PpDAM5 and PpDAM6 as the period of the release of flower bud endodormancy approached. In addition, PpTCP20 interacted with PpABF2 to form heterodimers to regulate bud endodormancy, and the content of abscisic acid decreased with the release of endodormancy. PpTCP20 also inhibited expression of PpABF2 to regulate endodormancy. Taken together, our results suggest that PpTCP20 regulates peach flower bud endodormancy by negatively regulating the expression of PpDAM5 and PpDAM6, and by interacting with PpABF2, thus revealing a novel regulatory mechanism in a perennial deciduous tree.

Identification and characterization of cherry (Cerasus pseudocerasus G. Don) genes responding to parthenocarpy induced by GA3 through transcriptome analysis.

BACKGROUND: Fruit set after successful pollination is key for the production of sweet cherries, and a low fruit-setting rate is the main problem in production of this crop. As gibberellin treatment can directly induce parthenogenesis and satisfy the hormone requirement during fruit growth and development, such treatment is an important strategy for improving the fruit-setting rate of sweet cherries. Previous studies have mainly focused on physiological aspects, such as fruit quality, fruit size, and anatomical structure, whereas the molecular mechanism remains clear. RESULTS: In this study, we analyzed the transcriptome of 'Meizao' sweet cherry fruit treated with gibberellin during the anthesis and hard-core periods to identify genes associated with parthenocarpic fruit set. A total of 25,341 genes were identified at the anthesis and hard-core stages, 765 (681 upregulated, 84 downregulated) and 186 (141 upregulated, 45 downregulated) of which were significant differentially expressed genes (DEGs) at the anthesis and the hard-core stages after gibberellin 3 (GA3) treatment, respectively. Based on DEGs between the control and GA3 treatments, the GA3 response mainly involves parthenocarpic fruit set and cell division. Exogenous gibberellin stimulated sweet cherry fruit parthenocarpy and enlargement, as verified by qRT-PCR results of related genes as well as the parthenocarpic fruit set and fruit size. Based on our research and previous studies in Arabidopsis thaliana, we identified key genes associated with parthenocarpic fruit set and cell division. Interestingly, we observed patterns among sweet cherry fruit setting-related DEGs, especially those associated with hormone balance, cytoskeleton formation and cell wall modification. CONCLUSIONS: Overall, the result provides a possible molecular mechanism regulating parthenocarpic fruit set that will be important for basic research and industrial development of sweet cherries.

Effects of ozone processing on patulin, phenolic compounds and organic acids in apple juice.

In this study, ozone processing was used to degrade patulin in apple juice, and the ozonolysis efficiency of patulin and its effects on phenolic compounds and organic acids in apple juice were investigated. Ozone processing was performed using a self-developed ozonolysis reactor at the ozone concentration of 12 mg/L and flow rate of 3 L/min for increasing ozonation times ranged from 0 to 30 min. Ozone processing significantly degraded patulin in apple juice, and decreased it from 201.06 to below 50 µg/L within 15 min, with a reduction of 75.36%. While major phenolic compounds and organic acids in apple juice were seriously destroyed by ozone processing compared with the control. Processors should consider the adverse effects of ozone processing on quality of apple juices and further studies are advised to optimize the ozone processing for remaining the phenols and organic acids in apple juices.

Dual-Responsive SPMA-Modified Polymer Photonic Crystals and Their Dynamic Display Patterns.

Light and electrothermal responsive polymer photonic crystals (PCs) modified with 1'-acryloyl chloride-3',3'-dimethyl-6-nitro-spiro(2H-1-benzopyran-2,2'-indoline) (SPMA) are proposed, and their dynamic display patterns are achieved through the combination of the SPMA-modified PCs and a patterned graphite layer. These PCs exhibit fluorescence under UV light irradiation because of the isomerization of the SPMA, which is restricted in the shell of the polymer colloidal spheres. After a voltage is applied to the patterned graphite layer, the fluorescence of PCs in the specific area disappears, and dynamic display patterns are obtained. Under UV light irradiation, the PCs change from the "partial-fluorescence" state to the initial "fluorescence" state, and the patterns disappear. Using this technique, the PC pattern "M L N" on the glass substrate and PC patterns from "0" to "9" on the paper substrate are fabricated. Thus, these dual-responsive PCs have potential applications in information recording, anticounterfeiting, dynamic display, and photoelectric devices.

Identification and characterization of Prunus persica miRNAs in response to UVB radiation in greenhouse through high-throughput sequencing.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression of target mRNAs involved in plant growth, development, and abiotic stress. As one of the most important model plants, peach (Prunus persica) has high agricultural significance and nutritional values. It is well adapted to be cultivated in greenhouse in which some auxiliary conditions like temperature, humidity, and UVB etc. are needed to ensure the fruit quality. However, little is known about the genomic information of P. persica under UVB supplement. Transcriptome and expression profiling data for this species are therefore important resources to better understand the biological mechanism of seed development, formation and plant adaptation to environmental change. Using a high-throughput miRNA sequencing, followed by qRT-PCR tests and physiological properties determination, we identified the responsive-miRNAs under low-dose UVB treatment and described the expression pattern and putative function of related miRNAs and target genes in chlorophyll and carbohydrate metabolism. RESULTS: A total of 164 known peach miRNAs belonging to 59 miRNA families and 109 putative novel miRNAs were identified. Some of these miRNAs were highly conserved in at least four other plant species. In total, 1794 and 1983 target genes for known and novel miRNAs were predicted, respectively. The differential expression profiles of miRNAs between the control and UVB-supplement group showed that UVB-responsive miRNAs were mainly involved in carbohydrate metabolism and signal transduction. UVB supplement stimulated peach to synthesize more chlorophyll and sugars, which was verified by qRT-PCR tests of related target genes and metabolites' content measurement. CONCLUSION: The high-throughput sequencing data provided the most comprehensive miRNAs resource available for peach study. Our results identified a series of differentially expressed miRNAs/target genes that were predicted to be low-dose UVB-responsive. The correlation between transcriptional profiles and metabolites contents in UVB supplement groups gave novel clues for the regulatory mechanism of miRNAs in Prunus. Low-dose UVB supplement could increase the chlorophyll and sugar (sorbitol) contents via miRNA-target genes and therefore improve the fruit quality in protected cultivation of peaches.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy.

Genome-wide identification of WRKY family genes in peach and analysis of WRKY expression during bud dormancy.

Bud dormancy in deciduous fruit trees is an important adaptive mechanism for their survival in cold climates. The WRKY genes participate in several developmental and physiological processes, including dormancy. However, the dormancy mechanisms of WRKY genes have not been studied in detail. We conducted a genome-wide analysis and identified 58 WRKY genes in peach. These putative genes were located on all eight chromosomes. In bioinformatics analyses, we compared the sequences of WRKY genes from peach, rice, and Arabidopsis. In a cluster analysis, the gene sequences formed three groups, of which group II was further divided into five subgroups. Gene structure was highly conserved within each group, especially in groups IId and III. Gene expression analyses by qRT-PCR showed that WRKY genes showed different expression patterns in peach buds during dormancy. The mean expression levels of six WRKY genes (Prupe.6G286000, Prupe.1G393000, Prupe.1G114800, Prupe.1G071400, Prupe.2G185100, and Prupe.2G307400) increased during endodormancy and decreased during ecodormancy, indicating that these six WRKY genes may play a role in dormancy in a perennial fruit tree. This information will be useful for selecting fruit trees with desirable dormancy characteristics or for manipulating dormancy in genetic engineering programs.

Single-step affinity and cost-effective purification of recombinant proteins using the Sepharose-binding lectin-tag from the mushroom Laetiporus sulphureus as fusion partner.

Previous research showed that a lectin from the mushroom Laetiporus sulphureus, designed LSL, bound to Sepharose and could be eluted by lactose. In this study, by taking advantage of the strong affinity of LSL-tag for Sepharose, we developed a single-step purification method for LSL-tagged fusion proteins. We utilized unmodified Sepharose-4B as a specific adsorbent and 0.2 M lactose solution as an elution buffer. Fusion proteins of LSL-tag and porcine circovirus capsid protein, designated LSL-Cap was recovered with purity of 90 ± 4%, and yield of 87 ± 3% from crude extract of recombinant Escherichia coli. To enable the remove of LSL-tag, tobacco etch virus (TEV) protease recognition sequence was placed downstream of LSL-tag in the expression vector, and LSL-tagged TEV protease, designated LSL-TEV, was also expressed in E. coli., and was recovered with purity of 82 ± 5%, and yield of 85 ± 2% from crude extract of recombinant E. coli. After digestion of LSL-tagged recombinant proteins with LSL-TEV, the LSL tag and LSL-TEV can be easily removed by passing the digested products through the Sepharose column. It is of worthy noting that the Sepharose can be reused after washing with PBS. The LSL affinity purification method enables rapid and inexpensive purification of LSL-tagged fusion proteins and scale-up production of native proteins.

Injury severity analysis of single-vehicle and two-vehicle crashes with electric scooters: A random parameters approach with heterogeneity in means and variances.

In recent years, the electric scooter has become one of the most popular means of transportation on short trips. Due to the lag in the formulation of transportation policies and regulations, coupled with the increasing number of electric scooter crashes, there has been growing concern about the safety of pedestrians and electric scooter riders. For the first time in the extant literature, this study aims to analyze injury severity of electric scooter crashes by unobserved heterogeneity modeling approaches. A random parameters approach with heterogeneity in means and variances is utilized to examine the factors influencing injury severity, using data collected from the STATS19 road safety database. Electric scooter crashes are classified as single-vehicle crashes and two-vehicle crashes, with injury severity categorized into two groups: fatalities or serious injuries, and slight injuries. The model estimation was conducted by considering several variables including roadway, environment, temporality, vehicle, and rider characteristics, as well as second-party vehicle and driver characteristics and manners of collision specific to two-vehicle crashes. The results of the model estimation reveal that certain factors had relatively stable effects with the varying degree of crash injury severity outcomes in both single-vehicle crashes and two-vehicle crashes. These factors include nighttime incidents, weekdays, male riders, and an increase in rider age, all of which are associated with more severe injury outcomes. Moreover, the random parameters logit model with heterogeneity in means and variances is more flexible in accounting for unobserved heterogeneity and exhibits better goodness of fit. This study improves the understanding of electric scooter safety, and the finding can better inform public policy regarding electric scooter use to improve road safety and reduce injury severity of electric scooter crashes.

Electrical storm: definitions, clinical importance, and treatment.

PURPOSE OF REVIEW: With increasing use of implantable cardioverter defibrillators, physicians are increasingly called upon to manage recurrent ventricular tachycardia, sometimes in the form of frequent recurrences known as electrical storm (or ventricular tachycardia storm). RECENT FINDINGS: Standard antiarrhythmic drug therapy may suppress storms, but, when refractory, interventions such as catheter ablation or in some cases surgical cardiac denervation may be helpful. Earlier interventional management may confer better outcomes than persisting with antiarrhythmic pharmacologic therapy. SUMMARY: The clinical syndrome of electrical storm has been defined empirically. An outcome-derived definition may better guide clinicians on when and how to treat this emergent problem. When available, an early interventional approach is preferred.

Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator.

The most effective pharmacological management of frequent ventricular tachyarrhythmia events in patients with an implantable defibrillator who failed or did not tolerate amiodarone is unknown. The aim of this retrospective cohort study was to assess the efficacy and tolerability of mexiletine in such patients. The patients served as self-controls. The number of treated ventricular tachyarrhythmia episodes (primary outcome); mortality, shocks from the defibrillator, and electrical storm events (secondary outcomes) during mexiletine therapy was compared with a matched duration of observation just before initiating mexiletine in 29 patients who were treated with a median dose of 300 mg/d of mexiletine and were followed for a median of 12 months. None of the patients had to stop mexiletine due to side effect. There was a significant reduction in the incidence of ventricular tachycardia/fibrillation episodes (median 2 vs. 12 events, P = 0.001) and shocks (median 0 vs. 2 events, P = 0.003) in the first 3 months of treatment, but long-term efficacy was only observed among patients who continued amiodarone therapy. In conclusion, mexiletine, when added to amiodarone in case of amiodarone inefficacy, reduces ventricular tachycardia/fibrillation events and appropriate therapies in patients with an implantable cardioverter defibrillator. A randomized trial should validate the efficacy and safety of mexiletine as an adjunctive therapy to amiodarone.

Genetic properties of endemic Chinese porcine epidemic diarrhea virus strains isolated since 2010.

Acute diarrhea outbreaks caused by porcine epidemic diarrhea virus (PEDV) have been observed in various pig-breeding provinces of China since December 2010. Endemic strains of PEDV were isolated from different areas, and the complete genome sequences of 10 isolates were determined. Our objective in this study was to genetically characterize current Chinese field isolates of PEDV to better understand their epidemiology and genetic diversity. Sequence analysis showed that 10 post-2010 isolates shared high homology with each other and were always clustered together with the virulent DR13 strains (South Korea) and/or one earlier Chinese strain, CH-S, in phylogenetic analysis. All post-2010 isolates possessed common sequence changes in each gene. Our results suggest that current Chinese PEDV isolates originated from either South Korean and/or Chinese ancestors that underwent some genetic variation, thereby forming a new PEDV genotype in China.

Isolation and genomic characterization of one novel goose astrovirus causing acute gosling gout in China.

Novel goose astrovirus (NGAstV) is a member of the genus Avain Avastrovirus (AAstV) and the family Astroviridae. NGAstV-associated gout disease has caused huge economic losses to the goose industry worldwide. Since early 2020, NGAstV infections characterized by articular and visceral gout emerged continuously in China. Herein, we isolated a GAstV strain from goslings with fatal gout disease and sequenced its complete genome nucleotide sequence. Then we conducted systematic genetic diversity and evolutionary analysis. The results demonstrated that two genotypic species of GAstV (GAstV-I and GAstV-II) were circulating in China, and GAstV-II sub-genotype IId had become the dominant one. Multiple alignments of amino acid sequences of GAstV capsid protein revealed that several characteristic mutations (E456D, A464N, and L540Q) in GAstV-II d strains, as well as additional residues in the newly identified isolate which varied over time. These findings enrich the understanding of the genetic diversity and evolution of GAstV and may facilitate the development of effective preventive strategies.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Klotho functionalization on vascular graft for improved patency and endothelialization.

The Klotho (KL) gene is related to aging. In this study, SKL (secreted KL) and heparin were cross-linked to the acellular small intestinal submucosa (SIS). Based on this, tissue-engineered bioactive small blood vessels were constructed. The goal of this study was to determine whether the release of SKL could improve the patency of small-diameter tissue-engineered blood vessels (TEVs) through promoting cell adhesion. The recombinant human SKL protein was generated from HEK293 cells with overexpression of SKL. Then the SIS membrane was cross-linked with heparin and SKL respectively, to prepare heparin group and SKL group artificial vascular grafts. SKL treatment promoted endothelial cells proliferation and upregulated the levels of Focal adhesion kinase (FAK) phosphorylation and Ras homolog gene family, member A (RhoA). SKL effectively enhanced the endothelial cells adhesion on the SIS membrane. In vivo evaluation of SKL modified SIS grafts in rabbits exhibited increased patency rate, endothelialization, and smooth muscle regeneration. In this study, SKL-modified SIS grafts can effectively improve patency of small-diameter TEVs through enhancing cell adhesion, and it is expected to exhibit an important effect in the construction of substitutes for coronary artery bypass grafting.

Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.

Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion. Here, we present the structure of infective GETV at a resolution of 2.8 Å with the atomic models of the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans indicate a possible impact on viral immune evasion and host cell invasion. The S-acylation sites might be involved in stabilizing the transmembrane assembly of E1 and E2. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The cholesterol and phospholipid stabilize the hydrophobic pocket in the viral envelope membrane. The structural information will assist structure-based antiviral and vaccine screening, design, and optimization.