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Interploidy hybridization between hexaploid and tetraploid genotypes occurred repeatedly during genomic introgression events throughout wheat evolution, and is commonly employed in wheat breeding programs. Hexaploid wheat usually serves as maternal parent because the reciprocal cross generates progeny with severe defects and poor seed germination, but the underlying mechanism is poorly understood. Here, we performed detailed analysis of phenotypic variation in endosperm between two interploidy reciprocal crosses arising from tetraploid (Triticum durum, AABB) and hexaploid wheat (Triticum aestivum, AABBDD). In the paternal- versus the maternal-excess cross, the timing of endosperm cellularization was delayed and starch granule accumulation in the endosperm was repressed, causing reduced germination percentage. The expression profiles of genes involved in nutrient metabolism differed strongly between these endosperm types. Furthermore, expression patterns of parental alleles were dramatically disturbed in interploidy versus intraploidy crosses, leading to increased number of imprinted genes. The endosperm-specific TaLFL2 showed a paternally imprinted expression pattern in interploidy crosses partially due to allele-specific DNA methylation. Paternal TaLFL2 binds to and represses a nutrient accumulation regulator TaNAC019, leading to reduced storage protein and starch accumulation during endosperm development in paternal-excess cross, as confirmed by interploidy crosses between tetraploid wild-type and clustered regularly interspaced palindromic repeats (CRISPR) - CRISPR-associated protein 9 generated hexaploid mutants. These findings reveal a contribution of genomic imprinting to paternal-excess interploidy hybridization barriers during wheat evolution history and explains why experienced breeders preferentially exploit maternal-excess interploidy crosses in wheat breeding programs., (© 2023 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Background: Aortic dissection (AD) is one of the crucial and common cardiovascular diseases, and pyroptosis is a novel cell delivery mechanism that is probably involved in the pathogenesis of various cardiovascular diseases. However, no study has investigated the role of pyroptosis in AD., Methods: We obtained two AD datasets, GSE153434 and GSE190635, from the Gene Expression Omnibus database. The differential expression of AD-related genes was determined by differential analysis, and their enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Additionally, a protein-protein interaction network was established. Next, potential biomarkers were screened by Lasso regression analysis, and a neural network model was constructed. Finally, the potential biomarkers were validated by constructing a mouse model of AD., Results: A total of 1033 differentially expressed related genes were distinguished and these genes were mainly associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase signaling pathways. The Lasso regression results showed five potential biomarkers, namely platelet endothelial cell adhesion molecule-1 (PECAM1), caspase 4 (CASP4), mixed lineage kinase domain-like pseudokinase (MLKL), APAF1-interacting protein (APIP), and histone deacetylase 6 (HDAC6) and successfully constructed a neural network model to predict AD occurrence. The results showed that CASP4 and MLKL were highly expressed, whereas PECAM1 and HDAC6 were lowly expressed in AD samples, and no statistically significant difference was observed in APIP expression in AD samples., Conclusion: Pyroptosis plays a crucial role in AD occurrence and development. Moreover, the five potential biomarkers identified in the present study can act as targets for the early diagnosis of AD in patients.

Aging is an inevitable process influenced by genetics, lifestyles, and environments. With the rapid social and economic development in recent decades, the proportion of the elderly has increased rapidly worldwide, and many aging-related diseases have shown an upward trend, including nervous system diseases, cardiovascular diseases, metabolic diseases, and cancer. The rising burden of aging-related diseases has become an urgent global health challenge and requires immediate attention and solutions. Natural products have been used for a long time to treat various human diseases. The primary cellular pathways that mediate the longevity-extending effects of natural products involve nutrient-sensing pathways. Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. Several studies have reviewed the effects of individual natural compounds on aging and aging-related diseases along with the underlying mechanisms. Natural products from food sources, such as polyphenols, saponins, alkaloids, and polysaccharides, are classified as antiaging compounds that promote health and prolong life via various mechanisms. In this article, we have reviewed several recently identified natural products with potential antiaging properties and have highlighted their cellular and molecular mechanisms. The discovery and use of dietary supplements and natural products that can prevent and treat multiple aging-related diseases in humans will be beneficial. Thus, this review provides theoretical background for existing dietary supplements and natural products as potential antiaging agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Liu, Luo, Lou, Li, Li and Liu.)

Background: Frailty is closely related to cancer. Previous research has shown that cancer patients are prone to frailty, and frailty increases the risk of adverse outcomes in cancer patients. However, it is unclear whether frailty increases the risk of cancer. This 2-sample Mendelian-randomization (MR) study sought to analyze the relationship between frailty and the risk of colon cancer., Methods: The database was extracted from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) in 2021. The genome-wide association study (GWAS) data related to colon cancer was obtained from the GWAS website (http://gwas.mrcieu.ac.uk/datasets), involving 462,933 individuals' gene information. Single-nucleotide polymorphisms (SNPs) were defined as the instrumental variables (IVs). The SNPs closely associated with the Frailty Index at a genome-wide significance level were selected. To further screen the IVs, we selected the confounding factors using the PhenoScanner (http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner). To estimate the causal effect of the Frailty Index on colon cancer, the MR-Egger regression, weighted median (WM1), inverse-variance weighted (IVW), and weight mode (WM2) methods were applied to calculate the SNP-frailty index and the SNP-cancer estimates. Cochran's Q statistic was used to estimate heterogeneity. The two-sample Mendelian randomization (TSMR) analysis was performed using the "TwoSampleMR" and "plyr" packages. All the statistical tests were 2-tailed, and a P value <0.05 was considered statistically significant., Results: We selected 8 SNPs as the IVs. The results of the IVW analysis [odds ratio (OR) =0.995, 95% confidence interval (CI): 0.990-1.001, P=0.052] showed that the genetic changes in the Frailty Index were not statistically associated with the risk of colon cancer, and no significant heterogeneity between these 8 genes was observed (Q =7.382, P=0.184). The MR-Egger (OR =0.987, 95% CI: 0.945-1.031, P=0.581), WM1 (OR =0.995, 95% CI: 0.990-1.001, P=0.118), WM2 (OR =0.996, 95% CI: 0.988-1.004, P=0.356), and SM (OR =0.996, 95% CI: 0.987-1.005, P=0.449) results were also consistent with each other. The sensitivity analysis based on the leave-one-out method showed that the individual SNPs did not affect the robustness of the results., Conclusions: Frailty might have no effect on the risk of colon cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-134/coif). The authors have no conflicts of interest to declare, (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Due to the prevalence of COVID-19, providing safe environments and reducing the risks of virus exposure play pivotal roles in our daily lives. Contact tracing is a well-established and widely-used approach to track and suppress the spread of viruses. Most digital contact tracing systems can detect direct face-to-face contact based on estimated proximity, without quantifying the exposed virus concentration. In particular, they rarely allow for quantitative analysis of indirect environmental exposure due to virus survival time in the air and constant airborne transmission. In this work, we propose an indoor spatiotemporal contact awareness framework (iSTCA), which explicitly considers the self-containing quantitative contact analytics approach with spatiotemporal information to provide accurate awareness of the virus quanta concentration in different origins at various times. Smartphone-based pedestrian dead reckoning (PDR) is employed to precisely detect the locations and trajectories for distance estimation and time assessment without the need to deploy extra infrastructure. The PDR technique we employ calibrates the accumulative error by identifying spatial landmarks automatically. We utilized a custom deep learning model composed of bidirectional long short-term memory (Bi-LSTM) and multi-head convolutional neural networks (CNNs) for extracting the local correlation and long-term dependency to recognize landmarks. By considering the spatial distance and time difference in an integrated manner, we can quantify the virus quanta concentration of the entire indoor environment at any time with all contributed virus particles. We conducted an extensive experiment based on practical scenarios to evaluate the performance of the proposed system, showing that the average positioning error is reduced to less than 0.7 m with high confidence and demonstrating the validity of our system for the virus quanta concentration quantification involving virus movement in a complex indoor environment.

Objective: To study the effect of dexmedetomidine (Dex) on perioperative inflammatory response in aortic dissection (AD) patients., Methods: From June 2020 to June 2022, 50 patients with Stanford type B AD underwent endovascular stent-graft exclusion (EVAR) at our hospital. They randomly were assigned to two groups (N = 25): the control group (C group) and the Dex group. Patients in the Dex group received 0.5ug/kg Dex intravenously 10 minutes before induction of anesthesia and 0.5µg/kg/h Dex during the intervention until 15 minutes before the end of surgery. In contrast, the C group received the same volume of normal saline at the same time points. The two groups were induced and maintained with the same anesthetic agents. Venous blood samples were taken 3 days before operation (T1), 1 day before operation (T2), 1 day after operation (T3) and 3 days after operation (T4) to detect levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC)., Results: At T3 and T4, CRP and ESR in the Dex group were significantly improved compared with those in the C group., Conclusion: Dexmedetomidine can reduce the inflammatory reaction of aortic dissection.

Background: This study aimed to explore the clinical significance of cellular senescence in uterine corpus endometrial carcinoma (UCEC)., Methods: Cluster analysis was performed on GEO data and TCGA data based on cellular senescence related genes, and then performed subtype analysis on differentially expressed genes between subtypes. The prognostic model was constructed using Lasso regression. Survival analysis, microenvironment analysis, immune analysis, mutation analysis, and drug susceptibility analysis were performed to evaluate the practical relevance. Ultimately, a clinical nomogram was constructed and cellular senescence-related genes expression was investigated by qRT-PCR., Results: We ultimately identified two subtypes. The prognostic model divides patients into high-risk and low-risk groups. There were notable discrepancies in prognosis, tumor microenvironment, immunity, and mutation between the two subtypes and groups. There was a notable connection between drug-sensitive and risk scores. The nomogram has good calibration with AUC values between 0.75-0.8. In addition, cellular senescence-related genes expression was investigated qRT-PCR., Conclusion: Our model and nomogram may effectively forecast patient prognosis and serve as a reference for patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Wang, Wang, Wang, Tang and Ji.)

Quantitative gene expression analysis by qPCR requires reference genes for normalization. Lagerstroemia indica (crape myrtle) is a popular ornamental plant in the world, but suitable endogenous reference genes are lacking. To find suitable reference genes, we evaluated the stabilities of nine candidate genes in six experimental data sets: six different tissues, three leaf colors, nine flower colors, and under three abiotic stresses (salt, drought, cold) using four statistical algorithms. A target gene LiMYB56 (homolog of Arabidopsis MYB56) was used to verify the authenticity and accuracy of the candidate reference genes. The results showed that the combination of two stably expressed reference genes, rather than a single reference gene, improved the accuracy of the qPCR. LiEF1α-2 + LiEF1α-3 was best for the tissue, salt treatment, and drought treatment sets; LiEF1α-2 + LiEF1α-1 was optimal for leaf color; LiEF1α-2 + LiACT7 was optimal for cold treatment; and LiUBC + LiEF1α-1 was best for the flower color set. Notably, LiEF1α-2 had high expression stability in all six experimental sets, implying it may be a good reference gene for expression studies in L. indica. Our results will facilitate future gene expression studies in L. indica.

GL1 is a golden-yellow leaf mutant that cultivated from natural bud-mutation of Lagerstroemia indica and has a very low level of photosynthetic pigment under sunlight. GL1 can gradually increase its pigment content and turn into pale-green leaf when shading under sunshade net (referred as Re-GL1). The mechanisms that cause leaf color variation are complicated and are not still unclear. Here, we have used a label-free comparative proteomics to investigate differences in proteins abundance and analyze the specific biological process associated with mechanisms of leaf color variation in GL1. A total of 245 and 160 proteins with different abundance were identified in GL1 vs WT and GL1 vs Re-GL1, respectively. Functional classification analysis revealed that the proteins with different abundance mainly related to photosynthesis, heat shock proteins, ribosome proteins, and oxidation-reduction. The proteins that the most significantly contributed to leaf color variation were photosynthetic proteins of PSII and PSI, which directly related to photooxidation and determined the photosynthetic performance of photosystem. Further analysis demonstrated that low jasmonic acid content was needed to golden-yellow leaf GL1. These findings lay a solid foundation for future studies into the molecular mechanisms that underlie leaf color formation of GL1. BIOLOGICAL SIGNIFICANCE: The natural bud mutant GL1 of L. indica is an example through changing leaf color to cope with complex environment. However, the molecular mechanism of leaf color variation are largely elusive. The proteins with different abundance identified from a label-free comparative proteomics revealed a range of biological processes associated with leaf color variation, including photosynthesis, oxidation-reduction and jasmonic acid signaling. The photooxidation and low level of jasmonic acid played a primary role in GL1 adaptation in golden-yellow leaf. These findings provide possible pathway or signal for the molecular mechanism associated with leaf color formation and as a valuable resource for signal transaction of chloroplast., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of competing interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Actinobacillus pleuropneumoniae is an important veterinary pathogen that causes porcine pleuropneumonia. Lipoproteins of bacterial pathogens play pleiotropic roles in the infection process. In addition, many bacterial lipoproteins are antigenic and immunoprotective. Therefore, characterization of lipoproteins is a promising strategy for identification of novel vaccine candidates or diagnostic markers. We cloned 58 lipoproteins from A. pleuropneumoniae JL03 (serovar 3) and expressed them in Escherichia coli. Five proteins with strong positive signals in western blotting analysis were used to immunize mice. These proteins elicited significant antibody responses, and three of them (APJL&#95;0922, APJL&#95;1380 and APJL&#95;1976) generated efficient immunoprotection in mice against lethal heterologous challenge with A. pleuropneumoniae 4074 (serovar 1), both in the active and passive immunization assays. Then immunogenicity of these three lipoproteins (APJL&#95;0922, APJL&#95;1380 and APJL&#95;1976) were further tested in pigs. Results showed that these proteins elicited considerable humoral immune responses and effective protective immunity against virulent A. pleuropneumoniae challenge. Our findings suggest that these three novel lipoproteins could be potential subunit vaccine candidates.

The highly conserved COP9 signalosome (CSN), composed of 8 subunits (Cops1 to Cops8), has been implicated in pluripotency maintenance of human embryonic stem cells (ESCs). Yet, the mechanism for the CSN to regulate pluripotency remains elusive. We previously showed that Cops2, independent of the CSN, is essential for the pluripotency maintenance of mouse ESCs. In this study, we set out to investigate how Cops5 and Cops8 regulate ESC differentiation and tried to establish Cops5 and Cops8 knockout (KO) ESC lines by CRISPR/Cas9. To our surprise, no Cops5 KO ESC clones were identified out of 127 clones, while three Cops8 KO ESC lines were established out of 70 clones. We then constructed an inducible Cops5 KO ESC line. Cops5 KO leads to decreased expression of the pluripotency marker Nanog, proliferation defect, G2/M cell-cycle arrest, and apoptosis of ESCs. Further analysis revealed dual roles of Cops5 in maintaining genomic stability of ESCs. On one hand, Cops5 suppresses the autophagic degradation of Mtch2 to direct cellular metabolism toward glycolysis and minimize reactive oxygen species (ROS) production, thereby reducing endogenous DNA damage. On the other hand, Cops5 is required for high DNA damage repair (DDR) activities in ESCs. Without Cops5, elevated ROS and reduced DDR activities lead to DNA damage accumulation in ESCs. Subsequently, p53 is activated to trigger G2/M arrest and apoptosis. Altogether, our studies reveal an essential role of Cops5 in maintaining genome integrity and self-renewal of ESCs by regulating cellular metabolism and DDR pathways., Competing Interests: The authors declare no competing interest.

Key Message: One QTL qLRI4 controlling leaf rolling index on chromosome 4 was finely mapped, and ZmOCL5, a member of the HD-Zip class IV genes, is likely a candidate. Leaf rolling is an important agronomic trait related to plant architecture that can change the light condition and photosynthetic efficiency of the population. Here, we isolated one EMS-induced mutant in Chang7-2 background with extreme abaxial rolling leaf, named abrl1. Histological analysis showed that the increased number and area of bulliform cells may contribute to abaxial rolling leaf in abrl1. The F 2 and F 2:3 populations derived from Wu9086 with flat leaves and abrl1 were developed to map abrl1. Non-Mendelian segregation of phenotypic variation was observed in these populations and five genomic regions controlling the leaf rolling index (LRI) were identified, which could be due to the phenotypic difference between Chang7-2 and Wu9086. Moreover, one major QTL qLRI4 on chromosome 4 was further validated and finely mapped to a genetic interval between InDel13 and InDel10, with a physical distance of approximately 277 kb using NIL populations, among which one 602-bp insertion was identified in the promoter region of HD-Zip class IV gene Zm00001d049443 (named as ZmOCL5) of abrl1 compared with wild-type Chang7-2. Remarkably, the 602-bp InDel was associated with LRI in an F 2 population developed by crossing abrl1 mutant and its wild-type. In addition, the 602-bp insertion increased ZmOCL5 promoter activity and expression. Haplotype analysis demonstrated that the 602-bp insertion was a rare mutation event. Taken together, we propose that the rolled leaf in the abrl1 mutant may be partially attributed to the 602-bp insertion, which may be an attractive target for the genetic improvement of LRI in maize.

Krüppel-homolog 1 (Kr-h1), a zinc-finger transcription factor, inhibits larval metamorphosis and promotes adult reproduction by transducing juvenile hormone (JH). Although the transcriptional regulation of Kr-h1 has been extensively studied, little is known about its regulation at the post-transcriptional level. Using the migratory locust Locusta migratoria as a model system, we report here that the microRNAs let-7 and miR-278 bound to the Kr-h1 coding sequence and downregulated its expression. Application of let-7 and miR-278 mimics (agomiRs) significantly reduced the level of Kr-h1 transcripts, resulting in partially precocious metamorphosis in nymphs as well as markedly decreased yolk protein precursors, arrested ovarian development and blocked oocyte maturation in adults. Moreover, the expression of let-7 and miR-278 was repressed by JH, constituting a regulatory loop of JH signaling. This study thus reveals a previously unknown regulatory mechanism whereby JH suppresses the expression of let-7 and miR-278, which, together with JH induction of Kr-h1 transcription, prevents the precocious metamorphosis of nymphs and stimulates the reproduction of adult females. These results advance our understanding of the coordination of JH and miRNA regulation in insect development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Genomic imprinting is an epigenetic phenomenon that causes genes to be differentially expressed depending on their parent of origin. To evaluate the evolutionary conservation of genomic imprinting and the effects of ploidy on this process, we investigated parent-of-origin-specific gene expression patterns in the endosperm of diploid ( Aegilops spp), tetraploid, and hexaploid wheat ( Triticum spp) at various stages of development via high-throughput transcriptome sequencing. We identified 91, 135, and 146 maternally or paternally expressed genes (MEGs or PEGs, respectively) in diploid, tetraploid, and hexaploid wheat, respectively, 52.7% of which exhibited dynamic expression patterns at different developmental stages. Gene Ontology enrichment analysis suggested that MEGs and PEGs were involved in metabolic processes and DNA-dependent transcription, respectively. Nearly half of the imprinted genes exhibited conserved expression patterns during wheat hexaploidization. In addition, 40% of the homoeolog pairs originating from whole-genome duplication were consistently maternally or paternally biased in the different subgenomes of hexaploid wheat. Furthermore, imprinted expression was found for 41.2% and 50.0% of homolog pairs that evolved by tandem duplication after genome duplication in tetraploid and hexaploid wheat, respectively. These results suggest that genomic imprinting was evolutionarily conserved between closely related Triticum and Aegilops species and in the face of polyploid hybridization between species in these genera., (© 2018 American Society of Plant Biologists. All rights reserved.)

Purpose: Provincial public drug formularies in Canada have different mechanisms for reimbursement of direct-acting oral anticoagulants (DOACs). We investigate how these differences influence DOAC utilization and expenditure across the country., Methods: We conducted a population-based, cross-sectional study of all out-patient prescriptions for OACs dispensed to public beneficiaries between January 1, 2010, and June 30, 2015. We calculated quarterly rates of OAC use and expenditures stratified by OAC type and province., Results: The greatest increase in quarterly rates of DOAC utilization occurred in provinces with more liberal mechanism of drug coverage: Ontario by 462%, Alberta by 425% and Quebec by 1,924%. This translated to increased expenditure on overall OAC by 270%, 204% and 390%, respectively. In contrast, provinces with more stringent mechanisms had low rates of DOAC utilization and expenditure., Conclusions: DOAC utilization and expenditure is considerably different across Canada, associated with provincial difference in reimbursement mechanism., (Copyright © 2017 Longwoods Publishing.)

Objective: To investigate the mitochondrial injury in enterovirus 71 (EV71)-infected Vero cells and explore the possible mechanism., Methods: A clinical isolate of EV71 was inoculated to Vero cells and the EV71 antigen was detected by immunofluorescence assay. The morphological changes of Vero cells were observed using optical microscopy and transmission electron microscopy. The diameter and area density of the viral particles and the ratio and area density of vacuolated mitochondria in the cells were measured on the ultrastructural images., Results: EV71-infected Vero cells underwent obvious changes and to a spherical morphology followed by cell death EV71 particles were detected in the cytoplasm by immunofluorescence. Ultrastructurally, the infected cells contained a large number of viral particles in the cytoplasm, with a clustered distribution and lattice-like arrangement. The diameter of the particles were 16.3 nm and the mean area density was 38.3%. Most of the mitochondria presented with swelling, vacuoles and degeneration. The ratio of the vacuolated mitochondria was 90.9% with a mean area density of 89.2%. Viral particles were also found in some mitochondria., Conclusion: EV71 proliferates in the cytoplasm and invades the mitochondria of infected Vero cells leading to mitochondrial injury and cell death, suggesting that mitochondria are the targets for EV71 infection.

Objective: To study the target organs for enterovirus 71 (EV71) in infected suckling mice., Methods: 5-day-old BALB/c suckling mice were infected with an EV71 strain. Tissues of the infected mice were processed for histopathological examination, including immunohistochemistry, in situ hybridization, ultrastructural observation., Results: Some mice developed limb paralysis, trouble walking and loss of balance. Results of the histopathological study showed that a large amount of EV71 existed in the skeletal muscle tissues, accounting for the damage of the skeletal muscles., Conclusion: The EV71 clinical isolate used in this study presented evident myotropism. Skeletal muscles are important target organs for EV71 in the infected suckling mice. To clarify the relationship between EV71 infection and muscle diseases may contribute to a better understanding of the pathogenesis of EV71.

We report an 8-month-old female infant with the fatal enterovirus 71 infection here. Clinically, she developed respiratory failure and severe pulmonary edema rapidly. Histologically, the lung specimen showed diffuse, severe pulmonary congestion and edema with focal intra-alveolar hemorrhage and typical features of acute encephalitis were easily identified under light microscope. Immunohistochemically, enterovirus 71 antigen was positive in the cerebella and brainstem. We measured the viral loads of different tissues and found that the brainstem and mesenteric lymph nodes showed the highest viral loads among all tissues. We hope that our case report may help to have a better understanding of the enterovirus 71 infection and provide clues to the prevention and treatment of this disease.

Numerous clinical and epidemiological reports indicate that patients with history of vascular illness such as stroke are more likely to develop dementia as the clinical manifestation of Alzheimer's disease. However, there are little data regarding the pathologic mechanisms that link vascular risk factors to the factors associated with dementia onset. We provide evidence that suggests intriguing detrimental interactions between stroke and β-amyloid (Aβ) toxicity in the hippocampus. Stroke was induced by unilateral striatal injection of endothelin-1, the potent vasoconstrictor. Aβ toxicity was modeled by bilateral intracerebroventricular injections of the toxic fragment Aβ. Gross morphologic changes in comorbid Aβ and stroke rats were enlargement of the lateral ventricles with concomitant shrinkage of the hippocampus. The hippocampus displayed a series of synergistic biochemical alterations, including microgliosis, deposition of Aβ precursor protein fragments, and cellular degeneration. In addition, there was bilateral induction of connexin43, reduced neuronal survival, and impaired dendritic development of adult-born immature neurons in the dentate gyrus of these rats compared with either rats alone. Behaviorally, there was impairment in the hippocampal-based discriminative fear-conditioning to context task indicating learning and memory deficit. These results suggest an insight into the relationship between hippocampal atrophy, pathology, and functional impairment. Our work not only highlights the exacerbated pathology that emerges when Aβ toxicity and stroke occur comorbidly but also demonstrates that this comorbid rat model exhibits physiopathology that is highly characteristic of the human condition., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The military population has a high disease burden of acute viral respiratory infections in China. To assess the efficacy and safety of a low-dose recombinant human interferon alpha-2b (rIFNalpha-2b) nasal spray in preventing acute viral respiratory infections in military population, we performed this randomized controlled trial. The results showed that application of the rIFNalpha-2b nasal spray had the benefits in prevention of infections caused by influenza A virus, influenza B virus parainfluenza viruses 1-3 and adenovirus species B. However, no benefit was seen in preventing respiratory syncytial virus. No severe adverse events were reported. Therefore, the rIFNalpha-2b nasal spray was effective and well tolerated for preventing common viral respiratory infections in the military recruits., (2010 Elsevier Ltd. All rights reserved.)