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حلم قرية دينغ : رواية
استنادا إلى فاعليات حقيقية وقعت بداية التسعينيات ؛ إذ أهلك مصيبة الإيدز قرى بأكملها، قرى سعى سكانها، بتحفيز من المسؤولين المحليين، الفرار من الفقر المدقع من خلال بيع الدم. وقائع قد تظهر من \"ديستوبيا\" متخيلة ؛ من فساد المسؤولين وصمت الحكام إلى تهديد الإنس وتسليعهم، ومن خبث التجار وانحطاط الأخلاق إلى جهل القرويين الحالمين بالثراء العاجل. تلك حكاية عن الوفاة والتنصل من المسؤوليات، عن جرائم بدون قصاص، عن جشع يمسخ علاقات الأسرة وأحلام كالنبوءات. بنثر آسر الحسن، ونبرة ولد بريء، نقرأ رواية \"يان ليانكه\"، وهو يؤسطر الزمان الماضي المطموس رسميا.
Book
Viral dynamics in mild and severe cases of COVID-19
Patients who had any of the following features at the time of, or after, admission were classified as severe cases: (1) respiratory distress (≥30 breaths per min); (2) oxygen saturation at rest ≤93%; (3) ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤300 mm Hg; or (4) severe disease complications (eg, respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure). Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected.4 No patient died from the infection. 23 (77%) of 30 severe cases received intensive care unit (ICU) treatment, whereas none of the mild cases required ICU treatment. All samples were collected according to WHO guidelines.5 The mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes.
Journal Article
Diplomacy of quasi-alliances in the Middle East
Quasi-alliance refers to the ideation, mechanism and behavior of policy-makers to carry out security cooperation through informal political and security arrangements. As a \"gray zone\" between alliance and neutrality, quasi-alliance is a hidden national security statecraft. Based on declassified archives and secondary sources, this book probes the theory and practice of quasi-alliances in the Middle East. Four cases are chosen to test the hypotheses of quasi-alliance, one of which is the Anglo-French-Israeli quasi-alliance during the Suez Canal War of 1956.
Book
HINT2 protects against pressure overload‐induced cardiac remodelling through mitochondrial pathways
Histidine triad nucleotide‐binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2‐overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload‐induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling.
Journal Article
Nanoconfinement steers nonradical pathway transition in single atom fenton-like catalysis for improving oxidant utilization
The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.
Nanoconfining single metal atom catalysts leads to faster decontamination, primarily due to improved interfacial mass transfer. This study identifies a change in the catalytic pathway as an additional significant factor contributing to the enhanced performance.
Journal Article
The inhibition by human MSCs-derived miRNA-124a overexpression exosomes in the proliferation and migration of rheumatoid arthritis-related fibroblast-like synoviocyte cell
Background
Rheumatoid arthritis is a long-term, progressive autoimmune disease. It is characterized by synovial hyperplasia leading to swelling, stiffness, and joint deformity in more than one joint. Fibroblast-like synoviocytes are the major cell types that make up the synovial intima structure, which is one of the decisive factors in the development and course of rheumatoid arthritis.
Methods
The potential therapeutic effects of MSCs-derived miRNA-124a overexpression exosomes were evaluated in vitro by the method including MTT assay and cell cycle test for cell proliferation, scratch wound closure and transwell for cell migration, flow cytometry and western for the apoptosis detection.
Results
Exosomes derived from human MSCs that overexpression miRNA-124a were prepared and characterized. We found that the pretreatment of this exosome was able to inhibit the proliferation and migration of fibroblast-like synoviocyte cell line and promote the apoptosis of this cell during the co-incubation.
Conclusions
Exosomes derived from MSCs were proved to be a suitable vector for the delivery of therapeutic miRNA-124a, and such miRNA-124a overexpression exosomes were expected to provide a new medicine and strategy for the treatment of rheumatoid arthritis.
Journal Article
Pathogenesis and transmission of SARS-CoV-2 in golden hamsters
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies
1
,
2
. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (
Mesocricetus auratus
). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6–7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.
The pathogenicity and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters resemble features of COVID-19 in human patients, suggesting that these hamsters could be used to model this disease.
Journal Article
East Asian origins of European holly oaks (Quercus section Ilex Loudon) via the Tibet-Himalaya
Aim Many subtropical organisms exhibit an East Asian‐Tethyan disjunction, a distribution split between East Asia and the Mediterranean. The underlying mechanisms and timing have remained unclear to date. The evolutionary history of Quercus section Ilex Loudon, a representative East Asian‐Tethyan disjunct lineage with a rich and widespread fossil record, was investigated to understand the key drivers of this disjunction. Location Eurasia. Methods The phylogeny of Quercus section Ilex was reconstructed using RAD‐seq. Divergence times were estimated based on three fossil calibrations. Ancestral range and niche were reconstructed on the calibrated tree to infer the timing of transitions in geographic distributions and niche. Convergence in ecological space was estimated by fitting alternative multiple‐regime Ornstein‐Uhlenbeck models. Leaf shape affinities among extant and fossil taxa of section Ilex were assessed using geometric morphometric approaches. Results Six clades were well resolved in section Ilex. Ancestral range reconstruction and divergence time dating suggest a wide distribution along the East Tethys seaway, with initial divergence at the mid‐Eocene, and all six clades originating before the Miocene. The section dispersed from East Asia to the Mediterranean at the Eocene‐Oligocene boundary. A shift toward higher elevations was detected in the Himalayan clade during the middle or late Miocene. European fossil lineages during the early Miocene differ in leaf morphology from later lineages, which we infer to be a consequence of adaptive differentiation or species turnover. Main conclusions Quercus section Ilex was widespread along the East Tethys seaway from the middle Eocene onward. The European holly oaks originated from an East Asian ancestral lineage that dispersed to Europe via the Tibet‐Himalaya corridor in the Oligocene. Lowlands along the margins of the Himalayas and through an Oligocene Tibetan valley served as the dispersal route(s) for these species. Changing climates drove Miocene extinction and local adaptation of European lineages.
Journal Article
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.
Journal Article
Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy
Background
Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN.
Methods
DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein–protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes.
Results
A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes.
Conclusion
We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.
Journal Article