The Role of CLEC-2 and Its Ligands in Thromboinflammation

C-type lectin-like receptor 2 (CLEC-2, also known as CLEC-1b) is expressed on platelets, Kupffer cells and other immune cells, and binds to various ligands including the mucin-like protein podoplanin (PDPN). The role of CLEC-2 in infection and immunity has become increasingly evident in recent years. CLEC-2 is involved in platelet activation, tumor cell metastasis, separation of blood/lymphatic vessels, and cerebrovascular patterning during embryonic development. In this review, we have discussed the role of CLEC-2 in thromboinflammation, and focused on the recent research

Efficient Point based Global Illumination on Intel MIC Architecture

International audiencePoint-Based Global Illumination (PBGI) is a popular rendering method in special effects and motion picture productions. The tree-cut computation is in general the most time consuming part of this algorithm, but it can be formulated for efficient parallel execution, in particular regarding wide-SIMD hardware. In this context, we propose several vectorization schemes, namely single, packet and hybrid, to maximize the utilization of modern CPU architectures. While for the single scheme, 16 nodes from the hierarchy are processed for a single receiver in parallel, the packet scheme handles one node for 16 receivers. These two schemes work well for scenes having smooth geometry and diffuse material. When the scene contains high frequency bumps maps and glossy reflections, we use a hybrid vectorization method. We conduct experiments on an Intel Many Integrated Corearchitecture and report preliminary results on several scenes, showing that up to a 3x speedup can be achieved when compared with non-vectorized execution

SHIP COLLISION RISK ASSESSMENT MODEL FOR QINZHOU PORT BASED ON EVENT SEQUENCE DIAGRAM

Qinzhou Port is one of the most important ports in the “Beibu Gulf” of China. It is also the main hub port of the "21st century maritime silk road" strategy. Based on a basic collision risk assessment approach, an Event Sequence Diagram (ESD) model that explains the four-stage collision avoidance decision-making procedure is proposed from the perspectives of perception, cognition, decision, and execution. Using the historical data derived from collision accident reports from the Qinzhou Port waters from 2013 to 2017, as well as the data elicited from expert knowledge, a quantitative evaluation of probability distributions of different collision failure modes is performed. The results are also compared with relevant results from other types of navigation waters to analyse collision risk level of Qinzhou waters. At the same time, the main failures paths of collision avoidance decision making are identified. The proposed model can provide with an overall collision risk picture from a macro perspective

Extending access to essential services against constraints: the three-tier health service delivery system in rural China (1949-1980).

BACKGROUND: China has made remarkable progress in scaling up essential services during the last six decades, making health care increasingly available in rural areas. This was partly achieved through the building of a three-tier health system in the 1950s, established as a linked network with health service facilities at county, township and village level, to extend services to the whole population. METHODS: We developed a Theory of Change to chart the policy context, contents and mechanisms that may have facilitated the establishment of the three-tier health service delivery system in rural China. We systematically synthesized the best available evidence on how China achieved universal access to essential services in resource-scarce rural settings, with a particular emphasis on the experiences learned before the 1980s, when the country suffered a particularly acute lack of resources. RESULTS: The search identified only three peered-reviewed articles that fit our criteria for scientific rigor. We therefore drew extensively on government policy documents, and triangulated them with other publications and key informant interviews. We found that China's three-tier health service delivery system was established in response to acute health challenges, including high fertility and mortality rates. Health system resources were extremely low in view of the needs and insufficient to extend access to even basic care. With strong political commitment to rural health and a "health-for-all" policy vision underlying implementation, a three-tier health service delivery model connecting villages, townships and counties was quickly established. We identified several factors that contributed to the success of the three-tier system in China: a realistic health human resource development strategy, use of mass campaigns as a vehicle to increase demand, an innovative financing mechanisms, public-private partnership models in the early stages of scale up, and an integrated approach to service delivery. An implementation process involving gradual adaptation and incorporation of the lessons learnt was also essential. CONCLUSIONS: China's 60 year experience in establishing a de-professionalized, community-based, health service delivery model that is economically feasible, institutionally and culturally appropriate mechanism can be useful to other low- and middle-income countries (LMICs) seeking to extend essential services. Lessons can be drawn from both reform content and from its implementation pathway, identifying the political, institutional and contextual factors shaping the three-tier delivery model over time

The global landscape and research trend of lymphangiogenesis in breast cancer: a bibliometric analysis and visualization

BackgroundBreast cancer persists as a major public health issue on a global scale. Lymphangiogenesis is an indispensable element in the promotion of breast cancer metastasis. Inhibiting the metastasis of breast cancer can be accomplished through targeting lymphangiogenesis. The purpose of this study was to examine research trends, major topics, and development directions of lymphangiogenesis in breast cancer through a bibliometric analysis, which may serve as a reference for future research and clinical practice.MethodsEnglish publications with article type article or review about lymphangiogenesis in breast cancer from inception to September 30, 2023, retrieved from the Web of Science Core Collection Database (WOSCC), and VOSviewer, CiteSpace, and Microsoft Excel were applied for bibliometric study.ResultsIn this paper, a total of 369 articles and reviews were included. The 369 papers were written by 2120 authors from 553 organizations across 42 countries, published in 199 journals, and cited 12458 references from 1801 journals up to September 30, 2023. Moreover, the annual publications had a rising trajectory between 2004 to 2014 but declined from 2015. The US was the leading nation in publications and citations. Meanwhile, academics Mousumi Majumder and Peeyush Lala had the highest cumulative number of publications. Based on the number of publications/citations, Cancer Research was the most influential journal. The most cited paper was “Lymphangiogenesis: Molecular Mechanisms and Future Promise” by Tuomas Tammela, published in the Journal of Cell. Additionally, keywords frequency analysis demonstrated that “lymphangiogenesis,” “breast cancer,” “VEGF-C,” “angiogenesis,” and “metastasis” were the most frequent keywords, and the newly emergent topics could be represented by “tumor microenvironment,” “metastasis,” “stem-cell,” “triple-negative breast cancer,” and “blood vessels.”ConclusionsCurrently, there is a strong research basis for lymphangiogenesis in breast cancer. The core research team was primarily situated in the US. Investigating the mechanism of lymphangiogenesis in breast cancer will always remain a highly discussed topic. In particular, it was essential to emphasize the relationship between lymphangiogenesis and tumor microenvironment, stem cells, triple-negative breast cancer, and metastasis, which could be the frontiers

Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2

Previous work found that the co-occurring mutations R203K/G204R on the SARS-CoV-2 nucleocapsid (N) protein are increasing in frequency among emerging variants of concern or interest. Through a combination of in silico analyses, this study demonstrates that R203K/G204R are adaptive, while large-scale phylogenetic analyses indicate that R203K/G204R associate with the emergence of the high-transmissibility SARS-CoV-2 lineage B.1.1.7. Competition experiments suggest that the 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly related to ribonucleocapsid (RNP) assembly. Moreover, the 203K/204R virus shows increased infectivity in human lung cells and hamsters. Accordingly, we observe a positive association between increased COVID-19 severity and sample frequency of 203K/204R. Our work suggests that the 203K/204R mutations contribute to the increased transmission and virulence of select SARS-CoV-2 variants. In addition to mutations in the spike protein, mutations in the nucleocapsid protein are important for viral spreading during the pandemic

Tumor Suppressor Spred2 Interaction with LC3 Promotes Autophagosome Maturation and Induces Autophagy-Dependent Cell Death

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner

PhDHS Is Involved in Chloroplast Development in Petunia

Deoxyhypusine synthase (DHS) is encoded by a nuclear gene and is the key enzyme involved in the post-translational activation of the eukaryotic translation initiation factor eIF5A. DHS plays important roles in plant growth and development. To gain a better understanding of DHS, the petunia (Petunia hybrida) PhDHS gene was isolated, and the role of PhDHS in plant growth was analyzed. PhDHS protein was localized to the nucleus and cytoplasm. Virus-mediated PhDHS silencing caused a sectored chlorotic leaf phenotype. Chlorophyll levels and photosystem II activity were reduced, and chloroplast development was abnormal in PhDHS-silenced leaves. In addition, PhDHS silencing resulted in extended leaf longevity and thick leaves. A proteome assay revealed that 308 proteins are upregulated and 266 proteins are downregulated in PhDHS-silenced plants compared with control, among the latter, 21 proteins of photosystem I and photosystem II and 12 thylakoid (thylakoid lumen and thylakoid membrane) proteins. In addition, the mRNA level of PheIF5A-1 significantly decreased in PhDHS-silenced plants, while that of another three PheIF5As were not significantly affected in PhDHS-silenced plants. Thus, silencing of PhDHS affects photosynthesis presumably as an indirect effect due to reduced expression of PheIF5A-1 in petunia.Significance:PhDHS-silenced plants develop yellow leaves and exhibit a reduced level of photosynthetic pigment in mesophyll cells. In addition, arrested development of chloroplasts is observed in the yellow leaves

The genome evolution and domestication of tropical fruit mango

Background: Mango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis. Results: We generate a chromosome-scale genome assembly of mango, providing a reference genome for the Anacardiaceae family. Our results indicate the occurrence of a recent whole-genome duplication (WGD) event in mango. Duplicated genes preferentially retained include photosynthetic, photorespiration, and lipid metabolic genes that may have provided adaptive advantages to sharp historical decreases in atmospheric carbon dioxide and global temperatures. A notable example of an extended gene family is the chalcone synthase (CHS) family of genes, and particular genes in this family show universally higher expression in peels than in flesh, likely for the biosynthesis of urushiols and related phenols. Genome resequencing reveals two distinct groups of mango varieties, with commercial varieties clustered with India germplasms and demonstrating allelic admixture, and indigenous varieties from Southeast Asia in the second group. Landraces indigenous in China formed distinct clades, and some showed admixture in genomes. Conclusions: Analysis of chromosome-scale mango genome sequences reveals photosynthesis and lipid metabolism are preferentially retained after a recent WGD event, and expansion of CHS genes is likely associated with urushiol biosynthesis in mango. Genome resequencing clarifies two groups of mango varieties, discovers allelic admixture in commercial varieties, and shows distinct genetic background of landraces

Highly Fluorinated Peptide Probes with Enhanced In Vivo Stability for 19^{19}F‐MRI

A labeling strategy for in vivo $^{19}$F-MRI (magnetic resonance imaging) based on highly fluorinated, short hydrophilic peptide probes, is developed. As dual-purpose probes, they are functionalized further by a fluorophore and an alkyne moiety for bioconjugation. High fluorination is achieved by three perfluoro-tert-butyl groups, introduced into asparagine analogues by chemically stable amide bond linkages. d-amino acids and β-alanine in the sequences endow the peptide probes with low cytotoxicity and high serum stability. This design also yielded unstructured peptides, rendering all 27 $^{19}$F substitutions chemically equivalent, giving rise to a single $^{19}$F-NMR resonance with <10 Hz linewidth. The resulting performance in $^{19}$F-MRI is demonstrated for six different peptide probes. Using fluorescence microscopy, these probes are found to exhibit high stability and long circulation times in living zebrafish embryos. Furthermore, the probes can be conjugated to bovine serum albumin with only amoderate increase in $^{19}$F-NMR linewidth to ≈30 Hz. Overall, these peptide probes are hence suitable for in vivo $^{19}$F-MRI applications