Near telomere-to-telomere genome assemblies of two Chlorella species unveil the composition and evolution of centromeres in green algae.

BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. CONCLUSIONS: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.

Protists regulate microbially mediated organic carbon turnover in soil aggregates.

Soil protists, the major predator of bacteria and fungi, shape the taxonomic and functional structure of soil microbiome via trophic regulation. However, how trophic interactions between protists and their prey influence microbially mediated soil organic carbon turnover remains largely unknown. Here, we investigated the protistan communities and microbial trophic interactions across different aggregates-size fractions in agricultural soil with long-term fertilization regimes. Our results showed that aggregate sizes significantly influenced the protistan community and microbial hierarchical interactions. Bacterivores were the predominant protistan functional group and were more abundant in macroaggregates and silt + clay than in microaggregates, while omnivores showed an opposite distribution pattern. Furthermore, partial least square path modeling revealed positive impacts of omnivores on the C-decomposition genes and soil organic matter (SOM) contents, while bacterivores displayed negative impacts. Microbial trophic interactions were intensive in macroaggregates and silt + clay but were restricted in microaggregates, as indicated by the intensity of protistan-bacterial associations and network complexity and connectivity. Cercozoan taxa were consistently identified as the keystone species in SOM degradation-related ecological clusters in macroaggregates and silt + clay, indicating the critical roles of protists in SOM degradation by regulating bacterial and fungal taxa. Chemical fertilization had a positive effect on soil C sequestration through suppressing SOM degradation-related ecological clusters in macroaggregate and silt + clay. Conversely, the associations between the trophic interactions and SOM contents were decoupled in microaggregates, suggesting limited microbial contributions to SOM turnovers. Our study demonstrates the importance of protists-driven trophic interactions on soil C cycling in agricultural ecosystems.

Linarin ameliorates ischemia-reperfusion injury by the inhibition of endoplasmic reticulum stress targeting AKR1B1.

Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.

VarEPS-Influ:an risk evaluation system of occurred and virtual variations of influenza virus genomes.

Influenza viruses undergo frequent genomic mutations, leading to potential cross-species transmission, phenotypic changes, and challenges in diagnostic reagents and vaccines. Accurately evaluating and predicting the risk of such variations remain significant challenges. To address this, we developed the VarEPS-Influ database, an influenza virus variations risk evaluation system (VarEPS-Influ). This database employs a 'multi-dimensional evaluation of mutations' strategy, utilizing various tools to assess the physical and chemical properties, primary, secondary, and tertiary structures, receptor affinity, antibody binding capacity, antigen epitopes, and other aspects of the variation's impact. Additionally, we consider space-time distribution, host species distribution, pedigree analysis, and frequency of mutations to provide a comprehensive risk evaluation of mutations and viruses. The VarEPS-Influ database evaluates both observed variations and virtual variations (variations that have not yet occurred), thereby addressing the time-lag issue in risk predictions. Our current one-stop evaluation system for influenza virus genomic variation integrates 1065290 sequences from 224 927 Influenza A, B and C isolates retrieved from public resources. Researchers can freely access the data at https://nmdc.cn/influvar/.

LiveRetro: Visual Analytics for Strategic Retrospect in Livestream E-Commerce.

Livestream e-commerce integrates live streaming and online shopping, allowing viewers to make purchases while watching. However, effective marketing strategies remain a challenge due to limited empirical research and subjective biases from the absence of quantitative data. Current tools fail to capture the interdependence between live performances and feedback. This study identified computational features, formulated design requirements, and developed LiveRetro, an interactive visual analytics system. It enables comprehensive retrospective analysis of livestream e-commerce for streamers, viewers, and merchandise. LiveRetro employs enhanced visualization and time-series forecasting models to align performance features and feedback, identifying influences at channel, merchandise, feature, and segment levels. Through case studies and expert interviews, the system provides deep insights into the relationship between live performance and streaming statistics, enabling efficient strategic analysis from multiple perspectives.

Thermally engineered MSC-derived extracellular vesicles ameliorate colitis in mice by restoring the imbalanced Th17/Treg cell ratio.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have garnered extensive interest for their immunomodulatory properties in immune-mediated inflammatory diseases. However, the development of EVs as clinical drugs often faces challenges such as low production yield and suboptimal therapeutic efficacy. In this study, we discovered that thermally engineering was able to enhance the yield of MSC-EVs. Moreover, the PD-L1 expression of EVs released from the thermal engineering MSCs was found to be upregulated significantly, and these EVs ameliorated the symptoms and pathological damages in murine dextran sulfate sodium (DSS)-induced colitis model. The therapeutic effect on DSS-induced colitis was mediated through the regulation of the Th17/Treg cell balance, demonstrating the immunomodulatory properties of the thermally engineering MSC-EVs. Overall, our findings suggest that thermal engineering can be utilized as a promising strategy for enhancing EV production and may provide a potential therapeutic approach for clinical treatment of colitis.

Integrating Network Pharmacology and Experimental Verification to Explore the Targets and Mechanism for Panax Notoginseng Saponins against Coronary In-stent Restenosis.

BACKGROUND: Despite widespread application of drug-eluting stents in coronary intervention, in-stent restenosis (ISR) is still a daunting complication in clinical practice. Panax notoginseng saponins (PNS) are considered to be effective herb compounds for preventing ISR. OBJECTIVE: This study aimed to elucidate the targets and mechanisms of PNS in ISR prevention using network pharmacology approaches and experimental verification. METHODS: Relevant targets of PNS active compounds were collected from the HERB database and PharmMapper. The ISR-related targets were obtained from the GeneCards database and the Comparative Toxicogenomics Database. The GO and KEGG enrichment analysis was performed using R software. The String database and Cytoscape software were employed to build the PPI and compounds-targets-pathways-disease networks. Finally, Molecular docking performed by Autodock Vina and cellular experiments were used to validate network pharmacology results. RESULTS: There were 40 common targets between PNS targets and ISR targets. GO analysis revealed that these targets focused on multiple ISR-related biological processes, including cell proliferation and migration, cell adhesion, inflammatory response, and anti-thrombosis and so on. The KEGG enrichment results suggested that PNS could regulate multiple signaling pathways to inhibit or delay the development and occurrence of ISR. The molecular docking and cellular experiments results verified the network pharmacology results. CONCLUSION: This study demonstrated that the potential molecular mechanisms of PNS for ISR prevention involved multiple compounds, targets, and pathways. These findings provide a theoretical reference and experimental basis for the clinical application and product development of PNS for the prevention of ISR.

Substrate Stiffness of Bone Microenvironment Controls Functions of Pre-Osteoblasts and Fibroblasts In Vitro.

The formation of bone in a bone defect is accomplished by osteoblasts, while the over activation of fibroblasts promotes fibrosis. However, it is not clear how the extracellular matrix stiffness of the bone-regeneration microenvironment affects the function of osteoblasts and fibroblasts. This study aim to investigate the effect of bone-regeneration microenvironment stiffness on cell adhesion, cell proliferation, cell differentiation, synthesizing matrix ability and its potential mechanisms in mechanotransduction, in pre-osteoblasts and fibroblasts. Polyacrylamide substrates mimicking the matrix stiffness of different stages of the bone-healing process (15 kPa, mimic granulation tissue; 35 kPa, mimic osteoid; 150 kPa, mimic calcified bone matrix) were prepared. Mouse pre-osteoblasts MC3T3-E1 and mouse fibroblasts NIH3T3 were plated on three types of substrates, respectively. There were significant differences in the adhesion of pre-osteoblasts and fibroblasts on different polyacrylamide substrates. Runx2 expression increased with increasing substrate stiffness in pre-osteoblasts, while no statistical differences were found in the Acta2 expression in fibroblasts on three substrates. OPN expression in pre-osteoblasts, as well as Fn1 and Col1a1 expression in fibroblasts, decreased with increasing stiffness. The difference between the cell traction force generated by pre-osteoblasts and fibroblasts on substrates was also found. Our results indicated that substrate stiffness is a potent regulator of pre-osteoblasts and fibroblasts with the ability of promoting osteogenic differentiation of pre-osteoblasts, while having no effect on myofibroblast differentiation of fibroblasts.

Therapeutic potential of apelin and Elabela in cardiovascular disease.

Apelin and Elabela (Ela) are peptides encoded by APLN and APELA, respectively, which act on their receptor APJ and play crucial roles in the body. Recent research has shown that they not only have important effects on the endocrine system, but also promote vascular development and maintain the homeostasis of myocardial cells. From a molecular biology perspective, we explored the roles of Ela and apelin in the cardiovascular system and summarized the mechanisms of apelin-APJ signaling in the progression of myocardial infarction, ischemia-reperfusion injury, atherosclerosis, pulmonary arterial hypertension, preeclampsia, and congenital heart disease. Evidences indicated that apelin and Ela play important roles in cardiovascular diseases, and there are many studies focused on developing apelin, Ela, and their analogues for clinical treatments. However, the literature on the therapeutic potential of apelin, Ela and their analogues and other APJ agonists in the cardiovascular system is still limited. This review summarized the regulatory pathways of apelin/ELA-APJ axis in cardiovascular function and cardiovascular-related diseases, and the therapeutic effects of their analogues in cardiovascular diseases were also included.

Potassium-rich antiperovskites K3HTe and K3FTe and their structural relation to lithium and sodium counterparts.

Unlike perovskite oxides, antiperovskites M3HCh and M3FCh (M = Li, Na; Ch = S, Se, Te) mostly retain their ideal cubic structure over a wide range of compositions owing to anionic size flexibility and low-energy phonon modes that promote their ionic conductivity. In this study, we show the synthesis of potassium-based antiperovskites K3HTe and K3FTe and discuss the structural features in comparison with lithium and sodium analogues. It is shown experimentally and theoretically that both compounds maintain a cubic symmetry and can be prepared at ambient pressure, in contrast to most of the reported M3HCh and M3FCh which require high pressure synthesis. A systematic comparison of a series of cubic M3HTe and M3FTe (M = Li, Na, K) revealed that telluride anions contract in the order of K, Na, Li, with a pronounced contraction in the Li system. This result can be understood in terms of the difference in charge density of alkali metal ions as well as the size flexibility of Ch anions, contributing to the stability of the cubic symmetry.

Plasmer: an Accurate and Sensitive Bacterial Plasmid Prediction Tool Based on Machine Learning of Shared k-mers and Genomic Features.

Identification of plasmids in bacterial genomes is critical for many factors, including horizontal gene transfer, antibiotic resistance genes, host-microbe interactions, cloning vectors, and industrial production. There are several in silico methods to predict plasmid sequences in assembled genomes. However, existing methods have evident shortcomings, such as unbalance in sensitivity and specificity, dependency on species-specific models, and performance reduction in sequences shorter than 10 kb, which has limited their scope of applicability. In this work, we proposed Plasmer, a novel plasmid predictor based on machine-learning of shared k-mers and genomic features. Unlike existing k-mer or genomic-feature based methods, Plasmer employs the random forest algorithm to make predictions using the percent of shared k-mers with plasmid and chromosome databases combined with other genomic features, including alignment E value and replicon distribution scores (RDS). Plasmer can predict on multiple species and has achieved an average the area under the curve (AUC) of 0.996 with accuracy of 98.4%. Compared to existing methods, tests of both sliding sequences and simulated and de novo assemblies have consistently shown that Plasmer has outperforming accuracy and stable performance across long and short contigs above 500 bp, demonstrating its applicability for fragmented assemblies. Plasmer also has excellent and balanced performance on both sensitivity and specificity (both >0.95 above 500 bp) with the highest F1-score, which has eliminated the bias on sensitivity or specificity that was common in existing methods. Plasmer also provides taxonomy classification to help identify the origin of plasmids. IMPORTANCE In this study, we proposed a novel plasmid prediction tool named Plasmer. Technically, unlike existing k-mer or genomic features-based methods, Plasmer is the first tool to combine the advantages of the percent of shared k-mers and the alignment score of genomic features. This has given Plasmer (i) evident improvement in performance compared to other methods, with the best F1-score and accuracy on sliding sequences, simulated contigs, and de novo assemblies; (ii) applicability for contigs above 500 bp with highest accuracy, enabling plasmid prediction in fragmented short-read assemblies; (iii) excellent and balanced performance between sensitivity and specificity (both >0.95 above 500 bp) with the highest F1-score, which eliminated the bias on sensitivity or specificity that commonly existed in other methods; and (iv) no dependency of species-specific training models. We believe that Plasmer provides a more reliable alternative for plasmid prediction in bacterial genome assemblies.

HiCAT: a tool for automatic annotation of centromere structure.

Significant improvements in long-read sequencing technologies have unlocked complex genomic areas, such as centromeres, in the genome and introduced the centromere annotation problem. Currently, centromeres are annotated in a semi-manual way. Here, we propose HiCAT, a generalizable automatic centromere annotation tool, based on hierarchical tandem repeat mining to facilitate decoding of centromere architecture. We apply HiCAT to simulated datasets, human CHM13-T2T and gapless Arabidopsis thaliana genomes. Our results are generally consistent with previous inferences but also greatly improve annotation continuity and reveal additional fine structures, demonstrating HiCAT's performance and general applicability.

Icariin Induces Triple-Negative Breast Cancer Cell Apoptosis and Suppresses Invasion by Inhibiting the JNK/c-Jun Signaling Pathway.

Background: Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive. Methods: The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc. Results: This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox-induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway. Conclusion: We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.

Phagotrophic Protists Modulate Copper Resistance of the Bacterial Community in Soil.

Protist predation is a crucial biotic driver modulating bacterial populations and functional traits. Previous studies using pure cultures have demonstrated that bacteria with copper (Cu) resistance exhibited fitness advantages over Cu-sensitive bacteria under the pressure of protist predation. However, the impact of diverse natural communities of protist grazers on bacterial Cu resistance in natural environments remains unknown. Here, we characterized the communities of phagotrophic protists in long-term Cu-contaminated soils and deciphered their potential ecological impacts on bacterial Cu resistance. Long-term field Cu pollution increased the relative abundances of most of the phagotrophic lineages in Cercozoa and Amoebozoa but reduced the relative abundance of Ciliophora. After accounting for soil properties and Cu pollution, phagotrophs were consistently identified as the most important predictor of the Cu-resistant (CuR) bacterial community. Phagotrophs positively contributed to the abundance of a Cu resistance gene (copA) through influencing the cumulative relative abundance of Cu-resistant and -sensitive ecological clusters. Microcosm experiments further confirmed the promotion effect of protist predation on bacterial Cu resistance. Our results indicate that the selection by protist predation can have a strong impact on the CuR bacterial community, which broadens our understanding of the ecological function of soil phagotrophic protists.

Preparation and Microstructure of High-Activity Spherical TaNbTiZr Refractory High-Entropy Alloy Powders.

High-activity spherical TaNbTiZr refractory high-entropy alloy (REHA) powders were successfully prepared by electrode induction melting gas atomization (EIGA) and plasma rotating electrode process (PREP) methods. Both the EIGAed and PREPed TaNbTiZr RHEA powders have a single-phase body-centered cubic (BCC) structure and low oxygen content. Compared with the EIGAed powders, the PREPed powders exhibit higher sphericity and smoother surface, but larger particle size. The average particle sizes of the EIGAed and PREPed powders are 51.8 and 65.9 µm, respectively. In addition, both the coarse EIGAed and PREPed powders have dendritic structure, and the dendrite size of the EIGAed powders is larger than that of the PREPed powders. Theoretical calculation indicates that the cooling rate of the PREPed powders is one order of magnitude higher than that of the EIGAed powders during the solidification process, and the dendritic structure has more time to grow during EIGA, which is the main reason for the coarser dendrite size of the EIGAed powders.

A monoamine oxidase B inhibitor ethyl ferulate suppresses microglia-mediated neuroinflammation and alleviates ischemic brain injury.

Microglia are the resident macrophages in the brain, which play a critical role in post-stroke neuroinflammation. Accordingly, targeting neuroinflammation could be a promising strategy to improve ischemic stroke outcomes. Ethyl ferulate (EF) has been confirmed to possess anti-inflammatory properties in several disease models, including acute lung injury, retinal damage and diabetes-associated renal injury. However, the effects of EF on microglial activation and the resolution of post-stroke neuroinflammation remains unknown. Here, we found that EF suppressed pro-inflammatory response triggered by lipopolysaccharide (LPS) stimulation in primary microglia and BV2 cell lines, as well as post-stroke neuroinflammation in an in vivo transient middle cerebral artery occlusion (tMCAO) stroke model in C57BL/6 mice, consequently ameliorating ischemic brain injury. Furthermore, EF could directly bind and inhibit the activity of monoamine oxidase B (MAO-B) to reduce pro-inflammatory response. Taken together, our study identified a MAO-B inhibitor, Ethyl ferulate, as an active compound with promising potentials for suppressing post-stroke neuroinflammation.

Bergapten attenuates microglia-mediated neuroinflammation and ischemic brain injury by targeting Kv1.3 and Carbonyl reductase 1.

Microglia-mediated neuroinflammation plays a vital role in the pathogenesis of ischemic stroke, which serves as a prime target for developing novel therapeutic agent. However, feasible and effective agents for controlling neuroinflammation are scarce. Bergapten were acknowledged to hold therapeutic potential in restricting inflammation in multiple diseases, including peripheral neuropathy, migraine headaches and osteoarthritis. Here, we aimed to investigate the impact of bergapten on microglia-mediated neuroinflammation and its therapeutic potential in ischemic stroke. Our study demonstrated that bergapten significantly reduced the expression of pro-inflammatory cytokines and the activation of NF-κB signaling pathway in LPS-stimulated primary microglia. Mechanistically, bergapten suppressed cellular potassium ion efflux by inhibiting Kv1.3 channel and inhibits the degradation of Carbonyl reductase 1 induced by LPS, which might contribute to the anti-inflammatory effect of bergapten. Furthermore, bergapten suppressed microglial activation and post-stroke neuroinflammation in an experimental stroke model, leading to reduced infarct size and improved functional recovery. Thus, our study identified that bergapten might be a potential therapeutic compound for the treatment of ischemic stroke.

Microstructure and Properties of a Graphene Reinforced Cu-Cr-Mg Composite.

To improve the graphene/copper interfacial bonding and the strength of the copper matrix, Cu-Cr-Mg alloy powder and graphene nanosheets (GNPs) have been used as raw materials in the preparation of a layered graphene/Cu-Cr-Mg composite through high-energy ball-milling and fast hot-pressing sintering. The microstructure of the composite after sintering, as well as the effect of graphene on the mechanical properties and conductivity of the composite, are also studied. The results show that the tensile strength of the composite material reached a value of 349 MPa, which is 46% higher than that of the copper matrix, and the reinforcement efficiency of graphene is as large as 136. Furthermore, the electrical conductivity of the composite material was 81.6% IACS, which is only 0.90% IACS lower than that of the copper matrix. The Cr and Mg elements are found to diffuse to the interface of the graphene/copper composite during sintering, and finely dispersed chromium carbide particles are found to significantly improve the interfacial bonding strength of the composite. Thus, graphene could effectively improve the mechanical properties of the composite while maintaining a high electrical conductivity.