Acute inducible ablation of GRP78 reveals its role in hematopoietic stem cell survival, lymphogenesis and regulation of stress signaling

GRP78, a master regulator of the unfolded protein response (UPR) and cell signaling, is required for inner cell mass survival during early embryonic development. However, little is known about its role in adult hematopoietic stem cells (HSCs) and hematopoiesis. Here we generated a conditional knockout mouse model that acutely deletes Grp78 in the adult hematopoietic system. Acute GRP78 ablation resulted in a significant reduction of HSCs, common lymphoid and myeloid progenitors, and lymphoid cell populations in the mutant mice. The GRP78-null induced reduction of the HSC pool could be attributed to increased apoptosis. Chimeric mice with Grp78 deletion only in the hematopoietic cells also showed a loss of HSCs and lymphopenia, suggesting a cell intrinsic effect. Analysis of GRP78 deficient bone marrow (BM) cells showed constitutive activation of all the major UPR signaling pathways, including activation of eIF2α, ATF6, xbp-1 splicing, as well as caspase activation. A multiplex cytokine assay further revealed alteration in select cytokine and chemokine serum levels in the mutant mice. Collectively, these studies demonstrate that GRP78 plays a pleiotropic role in BM cells and contributes to HSC survival and the maintenance of the lymphoid lineage.     

Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents

A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC₅₀) values of 70.3 and 53.65?μg/mL, respectively, which were much better than that of ribavirin (150.45?μg/mL), and 5aa was superior to ningnanmycin (EC₅₀?=?55.35?μg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (K_d) values of 22.6 and 9.8?μM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents.     

猕猴桃模板DNA的提取及RAPD-PCR最佳反应体系的建立

以改良CTAB法从猕猴桃叶片中制备模板DNA ,优化了PCR热循环参数 ,建立了RAPD PCR扩增的最佳反应体系。实验结果表明 ,CTAB提取液中EDTA组分的浓度对模板提取影响很大 ,其最适浓度为 80mmol/L ;用异丙醇沉淀后不经乙醇洗涤纯化的DNA不会影响扩增效果。PCR热循环参数为 :94℃预变性 5min ;94℃变性 1min ,37℃退火 1min ,72℃延伸 2min ,循环 4 0次 ;最后在 72℃延伸 6min。     

生物多样性国际发展援助作用、现状与中国行动思考:基于CBD履约视角

生物多样性国际发展援助是在全球范围达成《生物多样性公约》(Convention on Biological Diversity,CBD)目标和联合国可持续发展目标(Sustainable Development Goals,SDGs)的主要途径,也是中国在全球范围践行习近平生态文明思想、参与国际环境治理、维护中国海外发...     

Sequence determinants in the cathelicidin LL-37 that promote inflammation via presentation of RNA to scavenger receptors

Cathelicidins such as the human 37-amino acid peptide (LL-37) are peptides that not only potently kill microbes but also trigger inflammation by enabling immune recognition of endogenous nucleic acids. Here, a detailed structure–function analysis of LL-37 was performed to understand the details of this process. Alanine scanning of 34-amino acid peptide (LL-34) showed that some variants displayed increased antimicrobial activity against Staphylococcus aureus and group A Streptococcus. In contrast, different substitutions clustered on the hydrophobic face of the LL-34 alpha helix inhibited the ability of those variants to promote type 1 interferon expression in response to U1 RNA or to present U1 to the scavenger receptor (SR) B1 on the keratinocyte cell surface. Small-angle X-ray scattering experiments of the LL-34 variants LL-34, F5A, I24A, and L31A demonstrated that these peptides form cognate supramolecular structures with U1 characterized by inter-dsRNA spacings of approximately 3.5 nm, a range that has been previously shown to activate toll-like receptor 3 by the parent peptide LL-37. Therefore, while alanine substitutions on the hydrophobic face of LL-34 led to loss of binding to SRs and the complete loss of autoinflammatory responses in epithelial and endothelial cells, they did not inhibit the ability to organize with U1 RNA in solution to associate with toll-like receptor 3. These observations advance our understanding of how cathelicidin mediates the process of innate immune self-recognition to enable inert nucleic acids to trigger inflammation. We introduce the term “innate immune vetting” to describe the capacity of peptides such as LL-37 to enable certain nucleic acids to become an inflammatory stimulus through SR binding prior to cell internalization.     

不同生活型被子植物功能性状与基因组大小的关系

基因组大小在被子植物物种之间存在着巨大的变异, 但目前对不同生活型被子植物功能性状与基因组大小的关系缺乏统一的认识。本研究基于被子植物245科2,226属11,215个物种的基因组大小数据, 探讨了不同生活型物种种子重量、最大植株高度和叶片氮、磷含量4个功能性状与基因组大小之间的关系。结果表明, 被子植物最大植株高度和种子重量与基因组大小间的关系在草本和木本植物中存在显著差异。草本植物最大植株高度与基因组大小的关系不显著, 但种子重量与其呈极显著的正相关关系。木本植物最大植株高度与基因组大小显著负相关, 但种子重量与其关系不显著。木本植物叶片氮含量与基因组大小呈显著正相关, 但其他生活型植物的叶片氮、磷含量与基因组大小均无显著相关性。本研究表明被子植物功能性状与基因组大小的相关性在不同生活型间存在差异, 这为深入研究植物多种功能性状和植物生活型与基因组大小的权衡关系在植物演化和生态适应中的作用提供了重要依据。     

Unveiling The Multifunction of Beaded Stream-Like Co9Se8 Catalysts for Water Splitting,Reactive Oxygen Species Scavenging,and Hydrogen Anti-Inflammation

The electrocatalytic preparation of hydrogen at different pH values not only achieves excellent device performance but also promotes the application of reactive oxygen species (ROS) clearance and hydrogen anti-inflammation. However, it is difficult to develop materials that simultaneously achieve these excellent properties. Herein, the preparation of beaded necklace-like Co₉Se₈ microspheres using a general and facile synthetic strategy is reported. The Co₉Se₈-modified electrode has three applications: efficient water splitting for enhanced performance, ROS scavenging, and hydrogen anti-inflammatory activity. Experiments, high-angle-annular-dark-field scanning transmission electron microscopy, and density functional theory calculations indicate that the reconstructed Co(OH)₂ plays a vital role in the oxygen evolution reaction and that the transition from *O to *OOH is the actual rate-determining step. The Co₉Se₈ material, with its unique beaded necklace-like structure, exhibits exceptional hydrogen production capabilities in phosphate buffer solution (pH 7.4). In particular, hydrogen produce under neutral conditions can effectively reduce ROS levels and significantly inhibit inflammation-related pathological processes, playing a unique antioxidant and anti-inflammatory role at the cellular level. The obtained results indicate that the as-synthesized Co₉Se₈ is more suitable for water splitting, ROS scavenging, and hydrogen anti-inflammatory applications, outperforming other transition metal electrodes and rendering practical industrial and clinical applications.     

Efficiency Boost in All-Small-Molecule Organic Solar Cells: Insights from the Re-Ordering Kinetics

Achieving high-performance in all-small-molecule organic solar cells (ASM-OSCs) significantly relies on precise nanoscale phase separation through domain size manipulation in the active layer. Nonetheless, for ASM-OSC systems, forging a clear connection between the tuning of domain size and the intricacies of phase separation proves to be a formidable challenge. This study investigates the intricate interplay between domain size adjustment and the creation of optimal phase separation morphology, crucial for ASM-OSCs’ performance. It is demonstrated that exceptional phase separation in ASM-OSCs’ active layer is achieved by meticulously controlling the continuity and uniformity of domains via re-packing process. A series of halogen-substituted solvents (Fluorobenzene, Chlorobenzene, Bromobenzene, and Iodobenzene) is adopted to tune the re-packing kinetics, the ASM-OSCs treated with CB exhibited an impressive 16.2% power conversion efficiency (PCE). The PCE enhancement can be attributed to the gradual crystallization process, promoting a smoothly interconnected and uniformly distributed domain size. This, in turn, leads to a favorable phase separation morphology, enhanced charge transfer, extended carrier lifetime, and consequently, reduced recombination of free charges. The findings emphasize the pivotal role of re-packing kinetics in achieving optimal phase separation in ASM-OSCs, offering valuable insights for designing high-performance ASM-OSCs fabrication strategies.