Plant toxin β-ODAP activates integrin β1 and focal adhesion : a critical pathway to cause neurolathyrism

Neurolathyrism is a unique neurodegeneration disease caused by beta-N-oxalyl-L-alpha, beta-diaminopropionic (beta-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, beta-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+ from mitochondria to cellular matrix. Increased Ca2+ in cellular matrix activated the pathway of ECM, and brought about the overexpression of beta 1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change

Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>CD8⁺effector cells often have an antitumor function in patients with cancer. However, CD8⁺Foxp3⁺regulatory T cells (Tcregs) and interleukin (IL)-17-producing CD8⁺T cells (Tc17 cells) also derive from the CD8⁺T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8⁺Tcregs and Tc17 cells in NPC patients.</p> <p>Methods</p> <p>Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS) analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8⁺CD25⁺T cells with naïve CD4⁺T cells <it>in vitro</it>.</p> <p>Results</p> <p>We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs) and different distribution among peripheral blood mononuclear cells (PBMCs) in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor β, whereas Tc17 cells expressed a high level of tumor necrosis factor α. Interestingly, both subsets expressed a high level of interferon γ in TILs, and the Tcregs suppressed naïve CD4⁺T cell proliferation by a cell contact-dependent mechanism <it>in vitro</it>. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP) 1 and LMP2 antigen-specific Tcregs in NPC.</p> <p>Conclusions</p> <p>Our data provide new insights into the composition and function of CD8⁺T-cell subsets in NPC, which may have an important influence on NPC immunotherapy.</p

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury &nbsp;to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis

Atomic-layer-deposited ultrafine MoS2 nanocrystals on cobalt foam for efficient and stable electrochemical oxygen evolution

Ultrafine molybdenum sulfide (MoS2) nanocrystals are grown on a porous cobalt (Co) foam current collector by atomic layer deposition (ALD) using molybdenum hexacarbonyl and hydrogen sulfide as precursors. When used to catalyze the oxygen evolution reaction (OER), the optimal Co@MoS2 electrode, even with a MoS2 loading as small as 0.06 mg cm-2, exhibits a large cathodic shift of ca. 200 mV in the onset potential (the potential at which the current density is 5 mA cm-2), a low overpotential of only 270 mV to attain an anodic current density of 10 mA cm-2, much smaller charge transfer resistance and substantially improved long-term stability at both low and high current densities, with respect to the bare Co foam electrode, showing substantial promise for use as an efficient, low-cost and durable anode in water electrolyzers.L. F. Liu acknowledges the support of the FCT Investigator grant (no. IF/01595/2014) and the Exploratory grant (No. IF/01595/2014/CP1247/CT0001) from the Portuguese Foundation of Science & Technology (FCT). D. H. Xiong and W. Li are thankful for the financial support from Marie Curie Action COFUND fellowships (NanoTrainforGrowth, Grant Agreement no. 600375) under the FP7 framework. D. H. Xiong also acknowledges the financial support from the China Postdoctoral Science Foundation (No. 2015 T80847). This work was partly funded by the European Commission Horizon 2020 project "CritCat" (Grant Agreement No. 686053).info:eu-repo/semantics/publishedVersio

Lepton polarization correlations in B→K∗τ−τ+B \to K^* \tau^- \tau^+

In this work we will study the polarizations of both leptons ($\tau$) in the decay channel $B\to K^* \tau^- \tau^+$. In the case of the dileptonic inclusive decay $B\to K^* \ell^- \ell^+$, where apart from the polarization asymmetries of single lepton $\ell$, one can also observe the polarization asymmetries of both leptons simultaneously. If this sort of measurement is possible then we can have, apart from decay rate, FB asymmetry and the six single lepton polarization asymmetries (three each for $\ell^-$ and $\ell^+$), nine more double polarization asymmetries. This will give us a very useful tool in more strict testing of SM and the physics beyond. We discuss the double polarization asymmetries of $\tau$ leptons in the decay mode $B\to K^* \tau^- \tau^+$ within the SM and the Minimal Supersymmetric extensions of it.Comment: 21 pages, 21 figures; version to match paper to appear in PR

Asprellcosides B of Ilex asprella Inhibits Influenza A Virus Infection by Blocking the Hemagglutinin- Mediated Membrane Fusion

Ilex asprella is routinely used in China as a traditional medicinal herb to treat influenza (Flu). However, its specific antiviral activity and underlying molecular mechanism have not yet been determined. In this study, we sought to determine the antiviral activity and mechanism of Asprellcosides B, an active component extracted from Ilex asprella, and used against the influenza A virus cell culture. We also performed a computer-assisted structural modeling analysis and carried out surface plasmon resonance (SPR) experiments in the hope of determining the viral target of Asprellcosides B. Results from our studies show that Asprellcosides B reduced virus replication by up to 63% with an IC50 of about 9 μM. It also decreased the low pH-induced and virus-mediated hemolysis by 71% in vitro. Molecular docking simulation analysis suggested a possible binding of Asprellcosides B to the hemagglutinin (HA), which was confirmed by a surface plasmon resonance (SPR) assay. Altogether, our findings demonstrate that Asprellcosides B inhibits the influenza A virus, through a specific binding to the HA, resulting in the blockade of the HA-mediated membrane fusion

Hydrogen Sulfide Protects HUVECs against Hydrogen Peroxide Induced Mitochondrial Dysfunction and Oxidative Stress

10.1371/journal.pone.0053147PLoS ONE82

The exclusive B−>(K,K∗)ℓ+ℓ−B -> (K, K^*) \ell^+ \ell^- decays in a CP softly broken two Higgs doublet model

We study the differential branching ratio, forward-backward asymmetry, CP-violating asymmetry, CP-violating asymmetry in the forward-backward asymmetry and polarization asymmetries in the $B -> K \ell^+ \ell^-$ and $B -> K^* \ell^+ \ell^-$ decays in the context of a CP softly broken two Higgs doublet model. We analyze the dependencies of these observables on the model parameters by paying a special attention to the effects of neutral Higgs boson (NHB) exchanges and possible CP violating effects. We find that NHB effects are quite significant for both decays. A combined analysis of above-mentioned observables seems to be very promising as a testing ground for new physics beyond the SM, especially for the existence of the CP-violating phase in the theory.Comment: 23 pages, 26 eps figures, version to appear in Nucl. Phys.

Arsenic-phosphorus interactions in the soil-plant-microbe system: dynamics of uptake, suppression and toxicity to plants

High arsenic (As) concentrations in the soil, water and plant systems can pose a direct health risk to humans and ecosystems. Phosphate (Pi) ions strongly influence As availability in soil, its uptake and toxicity to plants. Better understanding of As(V)-Pi interactions in soils and plants will facilitate a potential remediation strategy for As contaminated soils, reducing As uptake by crop plants and toxicity to human populations via manipulation of soil Pi content. However, the As(V)-Pi interactions in soil-plant systems are complex, leading to contradictory findings among different studies. Therefore, this review investigates the role of soil type, soil properties, minerals, Pi levels in soil and plant, Pi transporters, mycorrhizal association and microbial activities on As-Pi interactions in soils and hydroponics, and uptake by plants, elucidate the key mechanisms, identify key knowledge gaps and recommend new research directions. Although Pi suppresses As uptake by plants in hydroponic systems, in soils it could either increase or decrease As availability and toxicity to plants depending on the soil types, properties and charge characteristics. In soil, As(V) availability is typically increased by the addition of Pi. At the root surface, the Pi transport system has high affinity for Pi over As(V). However, Pi concentration in plant influences the As transport from roots to shoots. Mycorrhizal association may reduce As uptake via a physiological shift to the mycorrhizal uptake pathway, which has a greater affinity for Pi over As(V) than the root epidermal uptake pathway