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Infectious clone vectors used widely in genetic research. While constructing soybean mosaic virus (SMV) clone vectors, we found that transformed Agrobacterium grew significantly different depending on the viral strains used. In particular, the clone vectors constructed with SMV SC15 significantly suppressed the growth of Agrobacterium. Recombinant and truncated virus vector experiments showed that the polymorphism of a P1 protein coding sequence of SC15 leads to the growth inhibition of Agrobacterium. But the lack of other protein encoding sequences, except for the sequence encoding coat protein, should reduce the ability of SC15 to suppress Agrobacterium growth. A vector (pCB301-attL-SC15P) compatible with the Gateway cloning system was constructed using this Agrobacterium inhibitory sequence. The results from the LR recombination reaction with pCB301-attL-SC15P and Agrobacterium transformation showed the valuable application potential of the Agrobacterium inhibitory sequence to serve as a negative screening factor for effective recombinant clone screening in Agrobacterium. [ABSTRACT FROM AUTHOR]

Soybean mosaic virus (SMV), a member of Potyvirus, is the most destructive and widespread viral disease in soybean production. Our earlier studies identified a soybean 40S ribosomal protein S8 (GmRPS8) using the 6K1 protein of SMV as the bait to screen a soybean cDNA library. The present study aims to identify the interactions between GmRPS8 and SMV and characterize the role of GmRPS8 in SMV infection in soybean. Expression analysis showed higher SMV-induced GmRPS8 expression levels in a susceptible soybean cultivar when compared with a resistant cultivar, suggesting that GmRPS8 was involved in the response to SMV in soybean. Subcellular localization showed that GmRPS8 was localized in the nucleus. Moreover, the yeast two-hybrid (Y2H) experiments showed that GmRPS8 only interacted with 6K1 among the eleven proteins encoded by SMV. The interaction between GmRPS8 and 6K1 was further verified by a bimolecular fluorescence complementation (BiFC) assay, and the interaction was localized in the nucleus. Furthermore, knockdown of GmRPS8 by a virus-induced gene silencing (VIGS) system retarded the growth and development of soybeans and inhibited the accumulation of SMV in soybeans. Together, these results showed that GmRPS8 interacts with 6K1 and contributes to soybean susceptibility to SMV. Our findings provide new insights for understanding the role of GmRPS8 in the SMV infection cycle, which could help reveal potyviral replication mechanisms. [ABSTRACT FROM AUTHOR]

Electrochemical CO2 reduction reaction (CO2RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e. cation effect). In contrast to the widely‐studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO2 electrolyzers. Herein, by studying the organic cation effect on CO2RR, we find that benzimidazolium cation (Beim+) significantly outperforms other commonly‐used nitrogenous cations (R4N+) in promoting C2+ (mainly C2H4) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim+ can synergistically boost the CO2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C2H4 production at an industrial‐scale current density of 331 mA cm−2 from CO2/pure water co‐electrolysis, thanks to the dual‐role of Beim+ in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO2RR through the structural design of polyelectrolytes. [ABSTRACT FROM AUTHOR]

Host proteins are essential during virus infection, and viral factors must target numerous host factors to complete their infectious cycle. The mature 6K1 protein of potyviruses is required for viral replication in plants. However, the interaction between 6K1 and host factors is poorly understood. The present study aims to identify the host interacting proteins of 6K1. Here, the 6K1 of Soybean mosaic virus (SMV) was used as the bait to screen a soybean cDNA library to gain insights about the interaction between 6K1 and host proteins. One hundred and twenty-seven 6K1 interactors were preliminarily identified, and they were classified into six groups, including defense-related, transport-related, metabolism-related, DNA binding, unknown, and membrane-related proteins. Then, thirty-nine proteins were cloned and merged into a prey vector to verify the interaction with 6K1, and thirty-three of these proteins were confirmed to interact with 6K1 by yeast two-hybrid (Y2H) assay. Of the thirty-three proteins, soybean pathogenesis-related protein 4 (GmPR4) and Bax inhibitor 1 (GmBI1) were chosen for further study. Their interactions with 6K1 were also confirmed by bimolecular fluorescence complementation (BiFC) assay. Subcellular localization showed that GmPR4 was localized to the cytoplasm and endoplasmic reticulum (ER), and GmBI1 was located in the ER. Moreover, both GmPR4 and GmBI1 were induced by SMV infection, ethylene and ER stress. The transient overexpression of GmPR4 and GmBI1 reduced SMV accumulation in tobacco, suggesting their involvement in the resistance to SMV. These results would contribute to exploring the mode of action of 6K1 in viral replication and improve our knowledge of the role of PR4 and BI1 in SMV response. [ABSTRACT FROM AUTHOR]

The resistance of different soybean varieties to the Chinese isolate SC3 of soybean mosaic virus (SMV) was systematically studied. However, the resistance of different germplasm sources is still poorly understood. We constructed an infectious DNA clone of SMV-SC3 (pSC3) and modified it to allow the expression of yellow fluorescence protein (YFP)/ red fluorescence protein (RFP) during viral infection. By using the infection of pSC3-RFP, we can classify the resistance of different soybean cultivars to SMV-SC3 to the extreme resistance that restricts initial viral replication and the resistance that allows viral replication in the initially inoculated cells but restricts further movement. Also, we tracked the SMV-SC3 infection in susceptible cultivar Nannong 1138-2 (NN1138-2) and found that the seed transmission of SMV to the offspring plants can be tracked and recorded by imaging the virus-driven expression of YFP. Overall, we reveal new aspects of soybean resistance to SMV-SC3 and provide an essential tool to study the infection and transmission of SMV-SC3, which will help decipher the genes involved in SMV pathogenesis and host resistance. [ABSTRACT FROM AUTHOR]

Key message: A putative candidate gene conferring resistance to SMV strain SC1 was identified on chromosome 2, and the linked marker was validated in soybean cultivars Soybean mosaic, caused by the soybean mosaic virus, is the most common disease in soybean and a significant impediment to soybean production in the Huanghuai and Yangtze River regions of China. Kefeng No.1, a soybean cultivar, showed high resistance to soybean mosaic virus strain (SC1) collected from Huanghuai and Yangtze River regions. Genetic analysis based on the Mendelian genic population derived from the cross Kefeng No.1 × Nannong 1138-2 revealed that Kefeng No.1 possesses a single dominant gene. Furthermore, genetic fine-mapping using an F2 population containing 281 individuals delimited resistant gene to a genomic region of 186 kb flanked by SSR markers BS020610 and BS020620 on chromosome 2. Within this region, there were 14 genes based on the Williams 82 reference genome. According to sequence analysis, six of the 14 genes have amino acid differences, and one of these genes is the Rsv4 allele designated as Rsc1-DR. The functional analysis of candidate genes using the bean pod mottle virus (BPMV)-induced gene silencing (VIGS) system revealed that Rsc1-DR was accountable for Kefeng No.1's resistance to SMV-SC1. Based on the genome sequence of Rsc1-DR, an Insertion/Deletion (InDel) molecular marker, JT0212, was developed and genotyped using 100 soybean cultivars, and the coincidence rate was 89%. The study enriched our understanding of the SMV resistance mechanism. The marker developed in this study could be directly used by the soybean breeders to select the genotypes with favorable alleles for making crosses, and also it will facilitate marker-assisted selection of SMV resistance in soybean breeding. [ABSTRACT FROM AUTHOR]

Transition metal‐based electrocatalysts will undergo surface reconstruction to form active oxyhydroxide‐based hybrids, which are regarded as the "true‐catalysts" for the oxygen evolution reaction (OER). Much effort has been devoted to understanding the surface reconstruction, but little on identifying the origin of the enhanced performance derived from the substrate effect. Herein, we report the electrochemical synthesis of amorphous CoOOH layers on the surface of various cobalt sulfides (CoSα), and identify that the reduced intermolecular energy gap (Δinter) between the valence band maximum (VBM) of CoOOH and the conduction band minimum (CBM) of CoSα can accelerate the formation of OER‐active high‐valent Co4+ species. The combination of electrochemical and in situ spectroscopic approaches, including cyclic voltammetry (CV), operando electron paramagnetic resonance (EPR) and Raman, reveals that Co species in the CoOOH/Co9S8 are more readily oxidized to CoO2/Co9S8 than in CoOOH and other CoOOH/CoSα. This work provides a new design principle for transition metal‐based OER electrocatalysts. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM. • Identified MAP3K1 as a driver gene for glioma infiltration by scRNA-Seq analysis. • MAP3K1/c-JUN signaling axis correlates with poor prognosis of glioma patients. • MAP3K1/c-JUN signaling axis regulates glioblastoma stem cells invasion. • MAP3K1/c-JUN signaling axis is a potential infiltrative glioma therapeutic target. [ABSTRACT FROM AUTHOR]

Cation identity in the electrolyte is known to have a critical influence on electrocatalytic CO 2 reduction reaction (CO 2 RR). However, the impact of cation aggregation state at the electrode/electrolyte interface, particularly for organic cations, remains unclear for CO 2 RR. In this study, we investigated the effect of the organic cation aggregation state, by examining the CO 2 RR behaviors over a copper (Cu) electrode, before and after the surface modification of a polyelectrolyte (i.e. , quaternary ammonia poly (N-methyl-piperidine-co-p-terphenyl) with grafted piperidinium cations), in an aqueous electrolyte with free-moving piperidinium (Pip+) cations. Immobilizing the Pip+ cations on Cu surface was found to effectively promote the CO 2 RR selectivity. The underlying cause was further explored by in-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy and electrochemical double-layer capacitance measurements, illustrating that the enhanced CO 2 RR performance was due to the change in electrode/electrolyte interface properties. These findings would contribute to further optimization of the electrode/electrolyte interface for efficient CO 2 RR. [ABSTRACT FROM AUTHOR]

Key message : Rsc15, a novel locus underlying soybean resistance to SMV, was fine mapped to a 95-kb region on chromosome 6. The Rsc15- mediated resistance is likely attributed to the gene GmPEX14 , the relative expression of which was highly correlated with the accumulation of H O along with the activities of POD and CAT during the early stages of SMV infection in RN-9. Abstract: Soybean mosaic virus (SMV) causes severe yield losses and seed quality deterioration in soybean [ Glycine max (L.) Merr.] worldwide. A series of single dominant SMV resistance genes have been identified on respective soybean chromosomes 2, 13 and 14, while one novel locus, Rsc15, underlying resistance to the virulent SMV strain SC15 from soybean cultivar RN-9 has been recently mapped to a 14.6-cM region on chromosome 6. However, candidate gene has not yet been identified within this region. In the present study, we aimed to fine map the Rsc15 region and identify candidate gene(s) for this invaluable locus. High-resolution fine-mapping revealed that the Rsc15 gene was located in a 95-kb genomic region which was flanked by the two simple sequence repeat (SSR) markers SSR_06_17 and BARCSOYSSR_06_0835. Allelic sequence comparison and expression profile analysis of candidate genes inferred that the gene Glyma.06g182600 (designated as GmPEX14) was the best candidate gene attributing for the resistance of Rsc15, and that genes encoding receptor-like kinase (RLK) (i.e., Glyma.06g175100 and Glyma.06g184400) and serine/threonine kinase (STK) (i.e., Glyma.06g182900 and Glyma.06g183500) were also potential candidates. High correlations were established between the relative expression level of GmPEX14 and the hydrogen peroxide (HO) concentration and activities of catalase (CAT) and peroxidase (POD) during the early stages of SMV-SC15 infection in RN-9. The results of the present study will be useful in marker-assisted breeding for SMV resistance and will lead to further understanding of the molecular mechanisms of host resistance against SMV. [ABSTRACT FROM AUTHOR]

The vacuum preloading method combining prefabricated vertical drains (PVDs) and surcharge preloading from vacuum pressure is widely used in the improvement of dredger fill foundation. However, a clogging effect arises within the soils around the PVDs during the vacuum preloading, which significantly affects the soil consolidation. Previous studies indicated that the organic matter and soil pH circumstance influence the soil-water interaction and soil microstructure. In order to investigate the influences of organic matter and soil pH on the consolidation of clayey dredger fill, a series of small scale vacuum preloading tests was conducted on soils with different organic contents and soil pH values. Subsequently, Scanning Electron Microscopy observation test and vane shear test were carried out to evaluate the effect of vacuum preloading consolidation. The results showed that a low organic content or a high soil pH is beneficial for soil consolidation by vacuum preloading method, resulting in a more compact microstructure and a greater vane strength. There are two actions on the organic matter during the vacuum preloading consolidation, namely, material migration and organic matter dissolution. The organic matter dissolution effect is predominate at soil pH > 9.1, so that the consolidation effect is improved. However, the material migration effect is predominate at pH = 8.1, clay particles and organic matter can be transported with the water flow and redeposit near the drain pipes, resulting in a clogging effect. Moreover, a higher pH can induce the change of microstructure from flocculated association to deflocculated and dispersed association of clay particles, which is positive to soil consolidation. The results in this paper may offer helpful references for engineering practice. [ABSTRACT FROM AUTHOR]

The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo , but not in vitro . Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression. [Copyright &y& Elsevier]

Glioblastoma (GBM) is the most common and fatal form of malignant brain tumor. Despite intensive effort, there is still no effective GBM treatment. Therefore, novel and more effective GBM therapeutic approaches are highly desired. In this study, we combined polymeric nanotechnology with microRNA (miRNA) regulation technology to develop a targeted polymeric nanoparticle to co-deliver anti-miR-21 and miR-124 into the brain to effectively treat GBM. The polymeric nanoparticle decorated with Angiopep-2 peptide not only can encapsulate miRNA via triple-interaction (electrostatic, hydrogen bond and hydrophobic bonding) to protect miRNA against enzyme degradation in the blood, but also is capable of crossing blood brain barrier (BBB) and allowing targeted delivery of miRNAs to GBM tissue due to the dual-targeting function of Angiopep-2. Moreover, the co-delivered anti-miR-21 and miR-124 simultaneously regulated the mutant RAS/PI3K/PTEN/AKT signaling pathway in tumor cells, consequently achieving combinatorial GBM therapy. This combinatorial effect was confirmed by our results showing that these miRNA nanomedicines can effectively reduce tumor cell proliferation, migration and invasion as well as reducing tumor angiogenesis. Consequently, effective suppression of tumor growth and significantly improved medium survival time are observed when these miRNA nanomedicines were assessed in an orthotopic GBM xenograft model. This work indicated that our new polymeric nanoparticles successfully mediate inhibition of miR-21 and miR-124 supplementation to significantly reduce tumorigenesis, and may have strong potential in GBM therapy. [ABSTRACT FROM AUTHOR]

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs., (© 2024. The Author(s).)

Glioblastoma is the most common type of malignant primary brain tumor and displays highly aggressive and heterogeneous phenotypes. The transcription factor STAT3 has been reported to play a key role in glioblastoma malignancy. Thus, discovering targets and functional downstream networks regulated by STAT3 that govern glioblastoma pathogenesis may lead to improved treatment strategies. In this study, we identified that poly(A)-specific ribonuclease (PARN), a key modulator of RNA metabolism, activates EGFR-STAT3 signaling to support glioblastoma stem cells (GSC). Functional integrative analysis of STAT3 found PARN as the top-scoring transcriptional target involved in RNA processing in patients with glioblastoma, and PARN expression was strongly correlated with poor patient survival and elevated malignancy. PARN positively regulated self-renewal and proliferation of GSCs through its 3'-5' exoribonuclease activity. EGFR was identified as a clinically relevant target of PARN in GSCs. PARN positively modulated EGFR by negatively regulating the EGFR-targeting miRNA miR-7, and increased EGFR expression created a positive feedback loop to increase STAT3 activation. PARN depletion in GSCs reduced infiltration and prolonged survival in orthotopic brain tumor xenografts; similar results were observed using siRNA nanocapsule-mediated PARN targeting. Pharmacological targeting of STAT3 also confirmed PARN regulation by STAT3 signaling. In sum, these results suggest that a STAT3-PARN regulatory network plays a pivotal role in tumor progression and thus may represent a target for glioblastoma therapeutics., Significance: A positive feedback loop comprising PARN and EGFR-STAT3 signaling supports self-renewal and proliferation of glioblastoma stem cells to drive tumor progression and can be targeted in glioblastoma therapeutics., (©2023 American Association for Cancer Research.)

Electrochemical CO 2 reduction reaction (CO 2 RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e., cation effect). In contrast to the widely-studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO 2 electrolyzers. Herein, by studying the organic cation effect on CO 2 RR, we find that benzimidazolium cation (Beim + ) significantly outperforms other commonly-used nitrogenous cations (R 4 N + ) in promoting C 2+ (mainly C 2 H 4 ) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim + can synergistically boost the CO 2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C 2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C 2 H 4 production at an industrial-scale current density of 331 mA cm -2 from CO 2 /pure water co-electrolysis, thanks to the dual-role of Beim + in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO 2 RR through the structural design of polyelectrolytes., (© 2023 Wiley-VCH GmbH.)

Adoptive chimeric antigen receptor (CAR) T cells designed to recognize specific tumor antigens have shown promising results in cancer therapy. While CAR T cell therapy has demonstrated notable clinical effectiveness for hematologic disease, efforts to develop therapies for solid tumors, including glioblastoma (GBM), have been hampered by heterogeneity, an immunosuppressive tumor microenvironment, and difficulty in trafficking. Several specific tumor antigens, such as IL13Rα2, EGFRvIII, and HER2, have been attempted in clinical trials; however, limited efficacy has been observed. In this review, we discuss the current status of CAR T therapy for GBM in clinical trials and highlight the potential target antigens for CAR T cells. Additionally, we summarize the mechanisms used to enhance their efficacy and explore the challenges and future prospects of CAR T cell therapy for GBM., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target., (© 2023. The Author(s).)

Soybean mosaic virus (SMV) is one of the most devastating viral pathogens of soybean (Glycine max (L.) Merr). In total, 22 Chinese SMV strains (SC1-SC22) have been classified based on the responses of 10 soybean cultivars to these pathogens. However, although several SMV-resistance loci in soybean have been identified, no gene conferring SMV resistance in the resistant soybean cultivar (cv.) Kefeng No.1 has been cloned and verified. Here, using F 2 -derived F 3 (F 2:3 ) and recombinant inbred line (RIL) populations from a cross between Kefeng No.1 and susceptible soybean cv. Nannong 1138-2, we localized the gene in Kefeng No.1 that mediated resistance to SMV-SC3 strain to a 90-kb interval on chromosome 2. To study the functions of candidate genes in this interval, we performed Bean pod mottle virus (BPMV)-induced gene silencing (VIGS). We identified a recombinant gene (which we named R SC3 K) harboring an internal deletion of a genomic DNA fragment partially flanking the LOC100526921 and LOC100812666 reference genes as the SMV-SC3 resistance gene. By shuffling genes between infectious SMV DNA clones based on the avirulent isolate SC3 and virulent isolate 1129, we determined that the viral protein P3 is the avirulence determinant mediating SMV-SC3 resistance on Kefeng No.1. P3 interacts with RNase proteins encoded by R SC3 K, LOC100526921, and LOC100812666. The recombinant R SC3 K conveys much higher anti-SMV activity than LOC100526921 and LOC100812666, although those two genes also encode proteins that inhibit SMV accumulation, as revealed by gene silencing in a susceptible cultivar and by overexpression in Nicotiana benthamiana. These findings demonstrate that R SC3 K mediates the resistance of Kefeng No.1 to SMV-SC3 and that SMV resistance of soybean is determined by the antiviral activity of RNase proteins., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

Background: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear. Methods: The mRNA expression data and clinical information of GBM and normal tissues were collected from the Chinese Glioma Genome Atlas The Cancer Genome Atlas (TCGA), and REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) cohorts. The DESeq2 R package was used to identify the differentially expressed genes between primary and recurrent GBM. ClueGO, Kyoto Encyclopedia of Genes and Genomes (KEGG), Biological Process in Gene ontology (GO-BP), and the Protein ANalysis THrough Evolutionary Relationships (PANTHER) pathway analyses were performed to explore the enriched signaling pathways in upregulated DEGs in recurrent GBM. A gene list that contained potential oncogenes that showed a significant negative correlation with patient survival from The Cancer Genome Atlas was used to further screen driver candidates for recurrent GBM. Univariate Cox proportional hazards regression analyses were used to investigate the risk score for the mRNA expression of the candidates. Single-cell RNA sequencing (scRNA-Seq) analyses were used to determine the cell type-specific distribution of Fc gamma receptor II b (FcγRIIb) in GBM. Immunohistochemistry (IHC) was used to confirm the FcγRIIb-positive cell populations in primary and paired recurrent GBM. Results: Through DEG analysis and overlap analysis, a total of 10 genes that are upregulated in recurrent GBM were screened. Using validation databases, FcγRIIb was identified from the 10 candidates that may serve as a driver for recurrent GBM. FCGR2B expression, not mutation, further showed a highly negative correlation with the poor prognosis of patients with recurrent GBM. Furthermore, scRNA-Seq analyses revealed that tumor-associated macrophage- and dendritic cell-specific FCGR2B was expressed. Moreover, FcγRIIb also showed a strong positive correlation coefficient with major immune-associated signaling pathways. In clinical specimens, FcγRIIb-positive cell populations were higher in recurrent GBM than in primary GBM. Conclusion: This study provides novel insights into the role of FcγRIIb in recurrent GBM and a promising strategy for treatment as an immune therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Kang, Lu, Guo, Liu, Zhang, Cui, Liu, Xu and Yin.)

Viral diseases of cultivated crops are often caused by virus spillover from wild plants. Tobacco ( N . tabacum ) is an important economic crop grown globally. The viral pathogens of tobacco are traditional major subjects in virology studies and key considerations in tobacco breeding practices. A positive-strand RNA virus, wild tomato mosaic virus (WTMV), belonging to the genus potyvirus in the family potyviridae was recently found to infect tobacco in China. In this study, diseased tobacco leaf samples were collected in the Henan Province of China during 2020-2021. Several samples from different locations were identified as WTMV positive. An infectious DNA clone was constructed based on one of the WTMV isolates. By using this clone, we found that WTMV from tobacco could establish infections on natural reservoir hosts, demonstrating a possible route of WTMV spillover and overwintering in the tobacco field. Furthermore, the WTMV infection was found to be accompanied by other tobacco viruses in the field. The co-inoculation experiments indicate the superinfection exclusion (SIE) between WTMV and other potyvirus species that infect tobacco. Overall, our work reveals novel aspects of WTMV evolution and infection in tobacco and provides an important tool for further studies of WTMV.

Glioblastoma (GBM) is the most common malignant brain tumor. The poor clinical outcome and overall ineffectiveness of current standard treatments, including surgery, chemotherapy, and radiation, highlight the urgent need for alternative tumor-specific therapies for GBM. Chimeric antigen receptor (CAR) T cell therapy is a revolutionary therapeutic strategy for hematological malignancies, but the optimal potency of CAR T cell therapy for solid tumors, especially GBM, has not been achieved. Although CAR T cell therapeutic strategies for GBM have been assessed in clinical trials, the current antitumor activity of CAR T cells remains insufficient. In this review, we present our perspective on genetically modifying CAR constructs, overcoming T cell dysfunctions, and developing additional treatments that can improve CAR T cell effectiveness, such as functionality, persistence, and infiltration into tumor sites. Effectively improved CAR T cells may offer patients with GBM new treatment opportunities, and this review is intended to provide a comprehensive overview for researchers to develop potent CAR T cells using genetic engineering or combinatorial preparations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Choi and Yin.)

Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Combinatorial therapy based on temozolomide (TMZ) and cisplatin (CDDP) shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood-brain-barrier (BBB) penetration, poor targeting of GBM tissue/cells, and systemic side effects, which hinder its efficacy in GBM therapy. To surmount these challenges, new GBM-cell membrane camouflaged and pH-sensitive biomimetic nanoparticles (MNPs) inspired by the fact that cancer cells readily pass the BBB and localize with homologous cells, are developed. This study's results show that MNPs can efficiently co-load TMZ and CDDP, transport these across the BBB to specifically target GBM. Incorporation of pH-sensitive polymer then allows for controlled release of drug cargos at GBM sites for combination drug therapy. Mice bearing orthotopic U87MG or drug-resistant U251 R GBM tumor and treated with MNPs@TMZ+CDDP show a potent anti-GBM effect, greatly extending the survival time relative to mice receiving single-drug loaded nanoparticles. No obvious side effects are apparent in histological analyses or blood routine studies. Considering these results, the study's new nanoparticle formulation overcomes multiple challenges currently limiting the efficacy of combined TMZ and CDDP GBM drug therapy and appears to be a promising strategy for future GBM combinatorial chemotherapy., (© 2022 Wiley-VCH GmbH.)

The alkaline polymer electrolyte fuel cells (APEFCs) hold great promise for using nonnoble metal-based electrocatalysts toward the cathodic oxygen reduction reaction (ORR), but are hindered by the sluggish anodic hydrogen oxidation reaction (HOR) in alkaline electrolytes. Here, a strategy is reported to promote the alkaline HOR performance of Ru by incorporating 3d-transition metals (V, Fe, Co, and Ni), where the conduction band minimum (CBM) level of Ru can be rationally tailored through strong d-d orbital coupling. As expected, the obtained RuFe nanosheet exhibits outstanding HOR performance with the mass activity of 233.46 A g PGM -1 and 23-fold higher than the Ru catalyst, even threefold higher than the commercial Pt/C. APEFC employing this RuFe as anodic catalyst gives a peak power density of 1.2 W cm -2 , outperforming the documented Pt-free anodic catalyst-based APEFCs. Experimental results and density functional theory calculations suggest the enhanced OH-binding energy and reduced formation energy of water derived from the downshifted CBM level of Ru contribute to the enhanced HOR activity., (© 2022 Wiley-VCH GmbH.)

E3-ubiquitin ligases are known to confer abiotic stress responses in plants. In the present study, GmPUB21 , a novel U-box E3-ubiquitin ligase-encoding gene, was isolated from soybean and functionally characterized. The expression of GmPUB21 , which possesses E3-ubiquitin ligase activity, was found to be significantly up-regulated by drought, salinity, and ABA treatments. The fusion protein GmPUB21-GFP was localized in the cytoplasm, nucleus, and plasma membrane. Transgenic lines of the Nicotiana benthamiana over-expressing GmPUB21 showed more sensitive to osmotic, salinity stress and ABA in seed germination and inhibited mannitol/NaCl-mediated stomatal closure. Moreover, higher reactive oxygen species accumulation was observed in GmPUB21 overexpressing plants after drought and salinity treatment than in wild-type (WT) plants. Contrarily, silencing of GmPUB21 in soybean plants significantly enhanced the tolerance to drought and salinity stresses. Collectively, our results revealed that GmPUB21 negatively regulates the drought and salinity tolerance by increasing the stomatal density and aperture via the ABA signaling pathway. These findings improved our understanding of the role of GmPUB21 under drought and salinity stresses in soybean.

The electrochemical CO 2 reduction over Cu catalysts has shown great potential in producing a wide range of valuable chemicals, but it is still plagued by a poor controllability on product distribution. Herein, we demonstrate an effective regulation of CO 2 reduction paths through a preanodization treatment of Cu foil electrodes in different electrolytes. The Cu electrode exhibits a superior C 1 and C 2+ product selectivity after being preanodized in NaClO 4 (Cu- NaClO 4 ) and Na 2 HPO 4 electrolyte (Cu- Na 2 HPO 4 ), respectively. Combined with in situ electrochemical Raman, ATR-SEIRAS, and SEM characterizations, the preferential C 1 path is due to the deposition of many Cu nanocrystals with dominant Cu(111) facets on the Cu- NaClO 4 electrode. In contrast, the preferential C 2+ path over the Cu- Na 2 HPO 4 is attributed to formation of a unique Cu nanodendritic morphology, which strengthens the *CO intermediate adsorption and induces an environment of low local H 2 O/CO 2 stoichiometric ratio, thus facilitating C-C coupling for C 2+ production. Our findings may shed light on the rational control of the CO 2 reduction path through engineering of the Cu surface structure.

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.

Background: Soybean mosaic virus (SMV) is one of the most devastating pathogens of soybean. MicroRNAs (miRNAs) are a class of non-coding RNAs (21-24 nucleotides) which are endogenously produced by the plant host as part of a general gene expression regulatory mechanisms, but also play roles in regulating plant defense against pathogens. However, miRNA-mediated plant response to SMV in soybean is not as well documented., Result: In this study, we analyzed 18 miRNA libraries, including three biological replicates from two soybean lines (Resistant and susceptible lines to SMV strain SC3 selected from the near-isogenic lines of Qihuang No. 1 × Nannong1138-2) after virus infection at three different time intervals (0 dpi, 7 dpi and 14 dpi). A total of 1,092 miRNAs, including 608 known miRNAs and 484 novel miRNAs were detected. Differential expression analyses identified the miRNAs profile changes during soybean-SMV interaction. Then, miRNAs potential target genes were predicted via data mining, and functional annotation was done by Gene Ontology (GO) analysis. The expression patterns of several miRNAs were validated by quantitative real-time PCR. We also validated the miRNA-target gene interaction by agrobacterium-mediated transient expression in Nicotiana benthamiana., Conclusion: We have identified a large number of miRNAs and their target genes and also functional annotations. We found that multiple miRNAs were differentially expressed in the two lines and targeted a series of NBS-LRR resistance genes. It is worth mentioning that many of these genes exist in the previous fine-mapping interval of the resistance gene locus. Our study provides additional information on soybean miRNAs and an insight into the role of miRNAs during SMV-infection in soybean., (© 2022. The Author(s).)

Soybean mosaic virus (SMV)-disease is one of the most serious and widespread diseases in soybean (Glycine max). In the present study, a DnaJ protein in soybean designated GmCPIP (SMV coat protein-interacting protein) was screened by the QIS-Seq (quantitative interactor screening with next-generation sequencing) method, and the interaction between SMV CP and GmCPIP was confirmed by the yeast two-hybrid (Y2H) system and bimolecular fluorescence complementation (BiFC) assay. Subcellular localization analysis indicated that both proteins are localized in the cytoplasm, cytomembrane and nucleus. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that infection with SMV-SC4 temporarily increased the transcription of GmCPIP. Virus-induced gene silencing (VIGS) down-regulated the GmCPIP gene by 82%, and the accumulation of SMV was decreased by 88.6% in GmCPIP-silenced plants inoculated with SMV-SC4. The interaction of GmCPIP with SMV CP seems to contribute to SMV infection in soybean., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This report focuses on a novel strategy for the preparation of transition metal-MoS 2 hybrid nanoclusters based on a one-step, dual-target magnetron sputtering, and gas condensation process demonstrated for Ni-MoS 2 . Aberration-corrected STEM images coupled with EDX analysis confirms the presence of Ni and MoS 2 in the hybrid nanoclusters (average diameter = 5.0 nm, Mo:S ratio = 1:1.8 ± 0.1). The Ni-MoS 2 nanoclusters display a 100 mV shift in the hydrogen evolution reaction (HER) onset potential and an almost 3-fold increase in exchange current density compared with the undoped MoS 2 nanoclusters, the latter effect in agreement with reported DFT calculations. This activity is only reached after air exposure of the Ni-MoS 2 hybrid nanoclusters, suggested by XPS measurements to originate from a Ni dopant atoms oxidation state conversion from metallic to 2+ characteristic of the NiO species active to the HER. Anodic stripping voltammetry (ASV) experiments on the Ni-MoS 2 hybrid nanoclusters confirm the presence of Ni-doped edge sites and reveal distinctive electrochemical features associated with both doped Mo-edge and doped S-edge sites which correlate with both their thermodynamic stability and relative abundance.

Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27(KIP1)-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27(KIP1) and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27(KIP1) and MMP3 expression., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)