Optimizing post-acute coronary syndrome (ACS) dyslipidemia management: Insights from the North American Acute Coronary Syndrome ACS Reflective III.

BACKGROUND: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aims to objectively investigate this evidence-to-practice care gap. Specifically, we aim 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 United States (U.S.) 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/U.S. 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. 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 one 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 are 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 may be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

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.

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.

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.

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.

Increased expression of interleukin-22 and its receptor is relevant to poor prognosis in laryngeal squamous cell carcinoma: A case control trial.

ABSTRACT: To detect the expression of interlerukin-22 (IL-22) and associated genes and to evaluate their relationship with clinicopathological features and prognosis in laryngeal squamous cell carcinoma (LSCC).The expression of IL-22 and associated genes were evaluated by immunohistochemistry and real time polymerase chain reaction in LSCC tissues from 30 patients and adjacent non-tumor tissues. A statistical analysis was implemented to assess the relationship among levels of expression, clinicopathological factors, and overall survival.The expression of IL-22 and interleukin 22 receptor 1 (IL-22R1) was mainly located in the cytoplasm, and the expression of LSCC was significantly higher than in controls. The expression of aryl hydrocarbon receptor and signal transducer and activator of transcription 3 distributed in the cell nucleus, which was significantly higher in LSCC than in controls. The expression of IL-22 and IL-22R1 was associated with metastasis of lymph node and clinical stage of LSCC. Overall survival of LSCC was significantly poorer with higher expression of IL-22 and IL-22R1 than in those with lower expression.The present research indicated that the increased level of IL-22 and IL-22R1 may be related to the pathogenesis and prognosis of LSCC. IL-22 may be the important biomarker, which need further research.

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.

MdBZR1 and MdBZR1-2like Transcription Factors Improves Salt Tolerance by Regulating Gibberellin Biosynthesis in Apple.

Brassinosteroids (BRs) are a group of plant steroid hormones that play important roles in regulating plant development. In addition, BRs show considerable functional redundancy with other plant hormones such as gibberellins (GAs). BRASSINAZOLE RESISTANT1 (BZR1) and BRI1-EMS-SUPPRESSOR1 (BES1) transcription factors are negative feedback regulators of BR biosynthesis. This study provides evidence for the roles of MdBZR1 and MdBZR1-2like in promoting GA production. These results also show that BRs regulate GA biosynthesis to improve salt tolerance in apple calli. Moreover, this research proposes a regulatory model, in which MdBZR1 and MdBZR1-2like bind to the promoters of GA biosynthetic genes to regulate their expression in a BR-dependent manner. The expression of key GA biosynthetic genes, MdGA20ox1, MdGA20ox2, and MdGA3ox1 in yeast helps to maintain normal growth even under intense salt stress. In summary, this study underscores the roles of MdBZR1 and MdBZR1-2like in improving salt tolerance by regulating GA biosynthesis in apple calli.

Corrigendum: Comparison Between Flat and Round Peaches, Genomic Evidences of Heterozygosity Events.

[This corrects the article DOI: 10.3389/fpls.2019.00592.].

Effects of nitrate deficiency on nitrate assimilation and chlorophyll synthesis of detached apple leaves.

Nitrogen is one of the most important nutrients for plant growth and development. Nitrate nitrogen (NO3--N) is the main form of nitrogen taken up by plants. Understanding the effects of exogenous NO3--N on nitrogen metabolism at the gene expression and enzyme activity levels during nitrogen assimilation and chlorophyll synthesis is important for increasing nitrogen utilization efficiency. In this study, cell morphology, NO3--N uptake rates, the expression of key genes related to nitrogen assimilation and chlorophyll synthesis and enzyme activity in apple leaves under NO3--N deficiency were investigated. The results showed that the cell morphology of apple leaves was irreversibly deformed due to NO3--N deficiency. NO3--N was absorbed slightly one day after NO3--N deficiency treatment and effluxed after 3 days. The relative expression of genes encoding nitrogen assimilation enzymes and the activity of such enzymes decreased significantly after 1 day of NO3--N deficiency treatment. After treatment for 14 days, gene expression was upregulated, enzyme activity was increased, and NO3--N content was increased. NO3--N deficiency hindered the transformation of 5-aminobilinic acid (ALA) to porphobilinogen (PBG), suggesting a possible route by which NO3--N levels affect chlorophyll synthesis. Collectively, the results indicate that NO3--N deficiency affects enzyme activity by altering the expression of key genes in the nitrogen assimilation pathway, thereby suppressing NO3--N absorption and assimilation. NO3--N deficiency inhibits the synthesis of the chlorophyll precursor PBG, thereby hindering chlorophyll synthesis.

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.

Comparison Between Flat and Round Peaches, Genomic Evidences of Heterozygosity Events.

Bud sports occur in many plant species, including fruit trees. Although they are correlated with genetic variance in somatic cells, the mechanisms responsible for bud sports are mostly unknown. In this study, a peach bud sport whose fruit shape was transformed to round from flat was identified by next generation sequencing (NGS), and we provide evidence that a long loss of heterozygosity (LOH) event may be responsible for this alteration in fruit shape. Moreover, compared to the reference genome, we identified 237,476 high quality single nucleotide polymorphisms (SNPs) in the wild-type and bud sport genomes. Using this SNP set, a long LOH event was identified at the distal end of scaffold Pp06 of the bud sport genome. Haplotypes from 155 additional peach accessions were phased, suggesting that the homozygous distal end of scaffold Pp06 of the bud sport was likely derived from only one haplotype of the wild-type flat peach. A genome-wide association study (GWAS) of 127 peach accessions was conducted to associate a SNP found at 26,924,482 bp of scaffold Pp06 to differences in fruit shape. All accessions with round-shaped fruit were found to have an A/A genotype, while those with A/T, or T/T genotypes had flat-shaped fruits. Finally, we also found that 236 peach accessions and 141 Prunus species with round-type fruit were found to have an A/A genotype at this SNP, while 22 flat peach accessions had an A/T genotype. Taken together, our results suggest that genes flanking this A/T polymorphism, and haplotyped carrying the T allele may determine flat fruit shape in this population. Furthermore, the LOH event resulting in the loss of the haplotype carrying the T allele may therefore be responsible for fruit shape alteration in wild-type flat peach.

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.

24-Epibrassinolide-alleviated drought stress damage influences antioxidant enzymes and autophagy changes in peach (Prunus persicae L.) leaves.

Drought stress is a serious threat to agriculture and the environment. Brassinosteroids (BRs) increase tolerance to drought stress of plant. Autophagy plays important roles in plant responses to drought stress; however, there are few reports on autophagy in peach (Prunus persica). In total, 23 putative autophagy-related genes (ATGs) in peach were identified using ATGs from the Arabidopsis thaliana genome as query in BLASTx algorithm-based searches. Under drought stress, the photosynthetic abilities of peach leaves decreased, while antioxidant enzyme activities, autophagy and ATG expression increased. A correlation analysis showed that antioxidant enzyme activities are inversely correlated to the expression levels of the PpATGs. During drought, the PpATG8s and some PpATG18s had the strongest responses. To investigate enhanced drought-stress tolerance, peach was treated with water, 100 nM 24-epibrassinolide (EBR), 1 µM EBR, 10 µM EBR and 1 µM voriconazole. Exogenous EBR at 1 µM decreased the malondialdehyde (MDA) content under drought stress when compared with water-, 1 µM voriconazole-, 100 nM EBR- and 10 µM EBR-treated peach leaf. The 1-µM EBR application increased superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX) and glutathione peroxidase (GR) activities during drought stress. In addition, the expression levels of PpATGs were inhibited by EBR. Thus, the 1-µM EBR treatment alleviated drought-stress damage to peach leaves, decreased PpATG expression levels and reduced the number of autophagosomes.

Fiber2 and hexon genes are closely associated with the virulence of the emerging and highly pathogenic fowl adenovirus 4.

Since May 2015, outbreaks of hydropericardium-hepatitis syndrome (HHS) caused by fowl adenovirus 4 (FAdV-4) with a novel genotype have been reported in China, causing significant economic losses to the poultry industry. A previous comparative analysis revealed that highly virulent FAdV-4 isolates contain various genomic deletions and multiple distinct mutations in the major structural genes fiber2 and hexon. To identify the genes responsible for the virulence of HHS-associated novel FAdV-4 isolates, FAdV-4 infectious clones were constructed by directly cloning the whole genome of a highly pathogenic FAdV-4 isolate (CH/HNJZ/2015) and that of a nonpathogenic strain (ON1) into a p15A-cm vector using the ExoCET method. Subsequently, the fiber2, hexon, and 1966-bp fragment-replaced mutant/recombinant viruses were constructed using Redαß recombineering and ccdB counter-selection techniques. The pathogenicity of the rescued viruses was compared with that of the rescued parent viruses rHNJZ and rON1 in 3-week-old SPF chickens. Chickens infected with the rescued viruses carrying the fiber2 and/or hexon gene of the HNJZ strain developed similar clinical signs to the natural infection, with distinctive gross lesions and characteristic histological signs indicative of HHS observed in sick/dead chickens. Our results clearly demonstrated that the virulence of the novel highly pathogenic FAdV-4 strain was independent of the 1966-bp deletion and that the fiber2 and hexon genes have crucial roles in FAdV-4 pathogenicity. The data presented in this report will provide further insights into the crucial factors determining the pathogenicity of FAdV strains. Furthermore, the infectious clones generated based on the FAdV-4 genome can be used as a platform for studies of gene function and for the development of recombinant vaccines.

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.