Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy

Wheat VQ Motif-Containing Protein VQ25-A Facilitates Leaf Senescence via the Abscisic Acid Pathway

Leaf senescence is an important factor affecting the functional transition from nutrient assimilation to nutrient remobilization in crops. The senescence of wheat leaves is of great significance for its yield and quality. In the leaf senescence process, transcriptional regulation is a committed step in integrating various senescence-related signals. Although the plant-specific transcriptional regulation factor valine-glutamine (VQ) gene family is known to participate in different physiological processes, its role in leaf senescence is poorly understood. We isolated TaVQ25-A and studied its function in leaf senescence regulation. TaVQ25-A was mainly expressed in the roots and leaves of wheat. The TaVQ25-A-GFP fusion protein was localized in the nuclei and cytoplasm of wheat protoplasts. A delayed senescence phenotype was observed after dark and abscisic acid (ABA) treatment in TaVQ25-A-silenced wheat plants. Conversely, overexpression of TaVQ25-A accelerated leaf senescence and led to hypersensitivity in ABA-induced leaf senescence in Arabidopsis. A WRKY type transcription factor, TaWRKY133, which is tightly related to the ABA pathway and affects the expression of some ABA-related genes, was found to interact with TaVQ25-A both in vitro and in vivo. Results of this study indicate that TaVQ25-A is a positive regulator of ABA-related leaf senescence and can be used as a candidate gene for wheat molecular breeding

A Schiff-Base Modified Pt Nano-Catalyst for Highly Efficient Synthesis of Aromatic Azo Compounds

A Schiff-base modified Pt nano-catalyst was prepared via one-pot aldimine condensation and then impregnation-reduction of a platinum precursor, in which the Pt nanoparticles (NPs) with an average size of 2.3 nm were highly dispersed on the support. The as-prepared catalyst exhibited excellent activity and selectivity in the hydrogenation coupling synthesis of aromatic azo compounds from nitroaromatic under mild conditions. The strong metal–support interaction derived from the coordination of nitrogen sites on Schiff-base to Pt NPs enables stabilizing the Pt NPs and achieving the catalytic recyclability. The scheme can also tolerate various functional groups and offer an efficient method for the green synthesis of aromatic azo compounds

Observing strain glass transition in Ti 33 Nb 15 Zr 25 Hf 25 O 2 high entropy alloy with Elinvar effect

Exploring the phase transition of high entropy alloys (HEAs) with multiple major elements is of great importance for understanding the underlying physical mechanisms. Macroscopic martensitic phase tran-sition has been frequently reported in HEAs, however, nanoscale microstructural phase evolution has not been investigated to the same extent. Herein, we have prepared the Ti33Nb15Zr25Hf25O2 HEA and investi-gated the strain glass transition and its associated properties using dynamic mechanical analysis and mi-crostructure characterization. We have found that the elastic modulus in Ti33Nb15Zr25Hf25O2 HEA deviates from Wachtman's equation and observed the Elinvar effect in the form of temperature-independent mod-ulus in the temperature range from 150 K to 450 K and frequency-dependence modulus around 220 K. The strain glass transition has been evidenced in Ti33Nb15Zr25Hf25O2 HEA by the formation and growth of nano-sized domains during in-situ transmission electron microscopy (TEM) cooling, and substantiated by the broken ergodicity during zero-field-cooling/field-cooling. The strain glass transition is believed to account for the Elinvar effect, where the modulus hardening of nano-sized domains compensates dynam-ically with the modulus softening of the transformable matrix.& COPY; 2023 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology

High-Quality Recrystallization of Amorphous Silicon on Si (100) Induced via Laser Annealing at the Nanoscale

At sub-3 nm nodes, the scaling of lateral devices represented by a fin field-effect transistor (FinFET) and gate-all-around field effect transistors (GAAFET) faces increasing technical challenges. At the same time, the development of vertical devices in the three-dimensional direction has excellent potential for scaling. However, existing vertical devices face two technical challenges: “self-alignment of gate and channel” and “precise gate length control”. A recrystallization-based vertical C-shaped-channel nanosheet field effect transistor (RC-VCNFET) was proposed, and related process modules were developed. The vertical nanosheet with an “exposed top” structure was successfully fabricated. Moreover, through physical characterization methods such as scanning electron microscopy (SEM), atomic force microscopy (AFM), conductive atomic force microscopy (C-AFM) and transmission electron microscopy (TEM), the influencing factors of the crystal structure of the vertical nanosheet were analyzed. This lays the foundation for fabricating high-performance and low-cost RC-VCNFETs devices in the future

Differential subgenome expression underlies biomass accumulation in allotetraploid Pennisetum giganteum

Abstract Background Pennisetum giganteum (AABB, 2n = 4x = 28) is a C4 plant in the genus Pennisetum with origin in Africa but currently also grown in Asia and America. It is a crucial forage and potential energy grass with significant advantages in yield, stress resistance, and environmental adaptation. However, the mechanisms underlying these advantageous traits remain largely unexplored. Here, we present a high-quality genome assembly of the allotetraploid P. giganteum aiming at providing insights into biomass accumulation. Results Our assembly has a genome size 2.03 Gb and contig N50 of 88.47 Mb that was further divided into A and B subgenomes. Genome evolution analysis revealed the evolutionary relationships across the Panicoideae subfamily lineages and identified numerous genome rearrangements that had occurred in P. giganteum. Comparative genomic analysis showed functional differentiation between the subgenomes. Transcriptome analysis found no subgenome dominance at the overall gene expression level; however, differentially expressed homoeologous genes and homoeolog-specific expressed genes between the two subgenomes were identified, suggesting that complementary effects between the A and B subgenomes contributed to biomass accumulation of P. giganteum. Besides, C4 photosynthesis-related genes were significantly expanded in P. giganteum and their sequences and expression patterns were highly conserved between the two subgenomes, implying that both subgenomes contributed greatly and almost equally to the highly efficient C4 photosynthesis in P. giganteum. We also identified key candidate genes in the C4 photosynthesis pathway that showed sustained high expression across all developmental stages of P. giganteum. Conclusions Our study provides important genomic resources for elucidating the genetic basis of advantageous traits in polyploid species, and facilitates further functional genomics research and genetic improvement of P. giganteum