4–1BB as a co-stimulatory receptor represents a next-generation therapeutic target in immune-oncology, which has been targeted by agonist antibodies or embedded in CAR-T cell construction. Notably, ...4–1BB activation requires cluster formation due to natural ligand association. However, precise and robust regulation of receptor clustering still encounters great challenges. Herein, we report a rationally designed self-assembled peptide ligand, composed of targeting and assembly modules, for in situ triggering ligand-receptor complex aggregation and augmenting clustering on T cells. The unique peptide ligand structure imparts ligand inter-crosslinking (LIC) effect that i) augments assembly rate by 3-fold upon binding to specific receptor of interest, ii) stabilizes ligand-receptor complex compared to both monomeric ligand and ligand aggregates, iii) triggers enhancement of pro-inflammatory cytokine release, cell viability and phosphorylation of transcription factor compared to binding-only molecule. Finally, the ligand also supplements anti-PD-1 therapy alone in CT26 syngeneic murine tumor model with controllable toxicity risk.
Display omitted
•4–1BB represents a next-generation therapeutic target in field of immunology oncology.•Effective activation of 4–1BB requires receptor high-order clustering.•A peptide ligand was reported to drive 4–1BB clustering for T cell activation.•Unique ligand shows ligand inter-crosslinking effect for effective and robust control.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recycled demolition waste (RDW) and ground granulated blast furnace slag-fly ash-based geopolymer (GFG) are promising materials for treating high-plasticity clay (CH) in highway subgrades. However, ...the underlying synergistic stabilization mechanisms remain unclear. To elucidate the fundamental mechanisms governing post-treatment soil stabilization, a multi-scale laboratory investigation was undertaken. This investigation encompassed the evaluation of mechanical properties (compaction, California bearing ratio (CBR), and unconfined compressive strength (UCS)) to quantify the enhanced performance of the treated soil. Additionally, microstructural and mineralogical characterization was performed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and atomic force microscopy (AFM) to elucidate the microscopic mechanisms responsible for this improvement. The results indicated that the addition of RDW led to a reduction in the optimum moisture content (OMC) while increasing the maximum dry density (MDD) of CH. Moreover, upon incorporating RDW-GFG, the mechanical properties of the cured soil exhibited significant improvement. Specifically, the addition of 25% RDW to CH resulted in a 184% increase in CBR and effective improvement in water stability (immersion swelling percentage is reduced). Furthermore, when 25% RDW and 15% GFG were added to CH, the UCS has increased significantly by 8 times. The addition of RDW effectively enhanced the particle size distribution, compacted the soil, thus increased the shear strength. The results from XRD and SEM analyses revealed that the inclusion of GFG could generate geopolymer cementitious bonding network in the soil matrix. These materials facilitated bonding between CH particles and RDW, filling the pores and densifying the overall structure, thus increasing its strength. The synergy of RDW-GFG substantially improved the highly plastic soil through physicochemical actions, markedly elevating both its strength and water stability. Consequently, the outcomes of this experimental study offer valuable insights for road engineering applications.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metal halide perovskite light-emitting diodes (PeLEDs) have been recognized as emerging candidates for next-generation solution-processed electronic display technology, and great progress has been ...made in recent years. However, their poor operational stability is yet to be solved. Here, we present a reformative all-inorganic red-emission PeLED based on the passivation effect caused by the incorporation of zinc ions into perovskites for enhancing the efficiency and operational stability. A high-quality quasi-two-dimensional perovskite CsPbI
3−
x
Br
x
thin film with good crystallinity is obtained, benefiting from the combination of large organic ammonium ions (PEA
+
ions) and inorganic salt zinc iodide (ZnI
2
). As a result, ZnI
2
-passivated CsPbI
3−
x
Br
x
PeLEDs emitting at 666 nm show a maximum external quantum efficiency of 9.93% and a maximum brightness of 4258 cd m
−2
. More importantly, the PeLEDs achieve a long half-lifetime of about 2667 h at an initial luminance of 100 cd m
−2
. This work provides a facile method to obtain stable and efficient red-emission PeLEDs.
Enhanced efficiency and operational stability are achieved for all-inorganic red perovskite light-emitting diodes using traces of zinc ions for defect passivation, leading to a prolonged half-lifetime up to 2667 hours.
Necroptosis is an alternative, caspase-independent programmed cell death that appears when apoptosis is inhibited. A gowing number of studies have reflected the link between necroptosis and tumors. ...However, only some systematical bibliometric analyses were focused on this field. In this study, we aimed to identify and visualize the cooperation between countries, institutions, authors, and journals through a bibliometric analysis to help understand the hotspot trends and emerging topics regarding necroptosis and cancer research.
The articles and reviews on necroptosis and cancer were obtained from the Web of Science Core Collection on 16 September 2022. Countries, institutions, authors, references, and keywords in this field were visually analyzed by CtieSpace 5.8.R3, VOSviewer 1.6.18, and R package "bibliometrix."
From 2006 to 2022, 2,216 qualified original articles and reviews on necroptosis in tumors were published in 685 academic journals by 13,009 authors in 789 institutions from 75 countries/regions. Publications focusing on necroptosis and cancer have increased violently in the past 16 years, while the citation number peaked around 2008-2011. Most publications were from China, while the United States maintained the dominant position as a "knowledge bridge" in necroptosis and cancer research; meanwhile, Ghent University and the Chinese Academy of Sciences were the most productive institutions. Moreover, only a tiny portion of the articles were multiple-country publications. Peter Vandenabeele had the most significant publications, while Alexei Degterev was most often co-cited. Peter Vandenabeele also gets the highest h-index and g-index in this research field. Cell Death and Disease was the journal with the most publications on necroptosis and cancer, which was confirmed to be the top core source by Bradford's Law. At the same time, Cell was the leading co-cited journal, and the focus area of these papers was molecular, biology, and immunology. High-frequency keywords mainly contained those that are molecularly related (MLKL, NF-kB, TNF, RIPK3, RIPK1), pathological process related (necroptosis, apoptosis, cell-death, necrosis, autophagy), and mechanism related (activation, expression, mechanisms, and inhibition).
This study comprehensively overviews necroptosis and cancer research using bibliometric and visual methods. Research related to necroptosis and cancer is flourishing. Cooperation and communication between countries and institutions must be further strengthened. The information in our paper would provide valuable references for scholars focusing on necroptosis and cancer.
Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of ...gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin.
DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze β-catenin ubiquitination.
Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKT
and GSK-3β
. Moreover, LPS induced phosphorylation of GSK-3β
in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic β-catenin, leading to β-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3β and β-catenin pathways.
This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.
SUMMARY
Iron deficiency is a major constraint for plant growth in calcareous soils. The interplay between NO
3
−
and Fe nutrition affects plant performance under Fe‐deficient conditions. However, how ...NO
3
−
negatively regulates Fe nutrition at the molecular level in plants remains elusive. Here, we showed that the key nitrate transporter NRT1.1 in Arabidopsis plants, especially in the shoots, was markedly downregulated at post‐translational levels by Fe deficiency. However, loss of NRT1.1 function alleviated Fe deficiency chlorosis, suggesting that downregulation of NRT1.1 by Fe deficiency favors plant tolerance to Fe deficiency. Further analysis showed that although disruption of NRT1.1 did not alter Fe levels in both the shoots and roots, it improved the reutilization of apoplastic Fe in shoots but not in roots. In addition, disruption of NRT1.1 prevented Fe deficiency‐induced apoplastic alkalization in shoots by inhibiting apoplastic H
+
depletion via NO
3
−
uptake.
In vitro
analysis showed that reduced pH facilitates release of cell wall‐bound Fe. Thus, foliar spray with an acidic buffer promoted the reutilization of Fe in the leaf apoplast to enhance plant tolerance to Fe deficiency, while the opposite was true for the foliar spray with a neutral buffer. Thus, downregulation of the shoot‐part function of NRT1.1 prevents apoplastic alkalization to ensure the reutilization of apoplastic Fe under Fe‐deficient conditions. Our findings may provide a basis for elucidating the link between N and Fe nutrition in plants and insight to scrutinize the relevance of shoot‐expressed NRT1.1 to the plant response to stress.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Schizophrenia patients have a high risk of suicide, and their cognition function is impaired with increasing age. The association between neurocognitive and suicidality in ...schizophrenia patients are heterogeneous. We aimed to explore the relationship between neurocognitive function and suicidal ideation in schizophrenia patients across age groups.
Methods
A total of 587 patients with schizophrenia were enrolled in this study. The schizophrenia patients were divided into young group (aged 18–44) and middle-aged and elderly group (aged 45–70). The schizophrenia patients were divided into suicidal ideation group and non-suicidal ideation group according to the evaluation results of the Beck Scale for Suicide Ideation. Insomnia symptoms were measured by the Insomnia Severity Index (ISI). Psychotic symptoms were measured by the Positive and Negative Syndrome Scale (PANSS), and cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Results
There was a negative correlation between the age and attention scores of RBANS (P = 0.018). The young schizophrenia patients had higher risk of suicidality than middle-aged and elderly schizophrenia patients (P = 0.001). In the logistic regression analysis, the scores of ISI and positive symptoms scores of PANSS were associated with suicidal ideation among young schizophrenia patients (All P < 0.05). Age, BMI, the scores of ISI, general symptoms scores of PANSS, visuospatial scores of RBANS and attention scores of RBANS were associated with suicidal ideation in middle-aged and elderly schizophrenia patients (All P < 0.05).
Conclusions
High visuospatial scores of RBANS and attention scores of RBANS were risk factors for suicidal ideation in middle-aged and elderly schizophrenia patients.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
