IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage

Fine root decomposition in forest ecosystems: an ecological perspective

Fine root decomposition is a physio-biochemical activity that is critical to the global carbon cycle (C) in forest ecosystems. It is crucial to investigate the mechanisms and factors that control fine root decomposition in forest ecosystems to understand their system-level carbon balance. This process can be influenced by several abiotic (e.g., mean annual temperature, mean annual precipitation, site elevation, stand age, salinity, soil pH) and biotic (e.g., microorganism, substrate quality) variables. Comparing decomposition rates within sites reveals positive impacts of nitrogen and phosphorus concentrations and negative effects of lignin concentration. Nevertheless, estimating the actual fine root breakdown is difficult due to inadequate methods, anthropogenic activities, and the impact of climate change. Herein, we propose that how fine root substrate and soil physiochemical characteristics interact with soil microorganisms to influence fine root decomposition. This review summarized the elements that influence this process, as well as the research methods used to investigate it. There is also need to study the influence of annual and seasonal changes affecting fine root decomposition. This cumulative evidence will provide information on temporal and spatial dynamics of forest ecosystems, and will determine how logging and reforestation affect fine root decomposition

COL5A2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer based on transcriptomics and single-cell RNA sequencing

Abstract Background There is still a therapeutic challenge in treating gastric cancer (GC) due to its high incidence and poor prognosis. Collagen type V alpha 2 (COL5A2) is increased in various cancers, yet it remains unclear how it contributes to the prognosis and immunity of GC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to download transcriptome profiling (TCGA-STAD; GSE84437), single-cell RNA sequencing (scRNA-seq) data (GSE167297) and clinical information. COL5A2 expression and its relationship with clinicopathological factors were analyzed. We conducted survival analysis and Cox regression analysis to evaluate the prognosis and independent factors of GC. Co-expressed analysis was also performed. To identify the underlying mechanism, we conducted analyses of differentially expressed genes (DEGs) and functional enrichment. The correlations between COL5A2 expression and immune cell infiltration levels and immune infiltrate gene marker sets were further explored. Additionally, we analyzed the association of COL5A2 expression with immunological checkpoint molecules. Furthermore, the relationship between COL5A2 expression and immunotherapy sensitivity was also investigated. Results COL5A2 expression was elevated in GC. More than this, the scRNA-seq analysis revealed that COL5A2 expression had a spatial gradient. The upregulated COL5A2 was associated with worse overall survival. A significant correlation was found between COL5A2 overexpression and age, T classification and clinical stage in GC. COL5A2 was found to be an independent factor for the unfortunate outcome in Cox regression analysis. The co-expressed genes of COL5A2 were associated with tumor stage or poor survival. Enrichment analysis revealed that the DEGs were mainly associated with extracellular matrix (ECM)-related processes, PI3K-AKT signaling pathway, and focal adhesion. GSEA analyses revealed that COL5A2 was associated with tumor progression-related pathways. Meanwhile, COL5A2 expression was correlated with tumor-infiltrating immune cells. Moreover, immunophenoscore (IPS) analysis and PRJEB25780 cohorts showed that patients with low COL5A2 expression were highly sensitive to immunotherapy. Conclusions COL5A2 might act as a prognostic biomarker of GC prognosis and immune infiltration and may provide a therapeutic intervention strategy

Structure-Tunable Construction of Colloidal Photonic Composites via Kinetically Controlled Supramolecular Crosslinking

Colloidal photonic composites (CPCs) combine a unique array of colloidal particles (CPs) with a polymer matrix and exhibit intriguing optical and mechanical properties strongly depending on their structures. One-step construction of CPCs with tunable structures is crucial for enriching their properties and matching application requirements, which is highly desirable yet challenging. Here, we present a general strategy for CPC construction with tunable structures from short-range to long-range order by one-step kinetically controlling the supramolecular crosslinking between CPs and supramolecular oligomers. Importantly, the assembly process is monitored in situ and the key factors for structural regulation, i.e., the critical volume fraction of CPs and the structural transition from crystal growth to lattice compression, are disclosed, which play critical roles in obtaining CPCs with a wide range of controllable structures. The as-obtained CPCs exhibit structural colors with different angle dependencies, versatile mechanical strengths, and appealing mechanochromic and self-healing capabilities. This work provides insights into the one-step construction of structure-tunable photonic materials, opening up exciting avenues for novel solution-processable photonics. © 2022 American Chemical Society. All rights reserved.11Nsciescopu

The Type VI Secretion System Engages a Redox-Regulated Dual-Functional Heme Transporter for Zinc Acquisition

The type VI secretion system was recently reported to be involved in zinc acquisition, but the underlying mechanism remains unclear. Here, we report that Burkholderia thailandensis T6SS4 is involved in zinc acquisition via secretion of a zinc-scavenging protein, TseZ, that interacts with the outer membrane heme transporter HmuR. We find that HmuR is a redox-regulated dual-functional transporter that transports heme iron under normal conditions but zinc upon sensing extracellular oxidative stress, triggered by formation of an intramolecular disulfide bond. Acting as the first line of defense against oxidative stress, HmuR not only guarantees an immediate response to the changing environment but also provides a fine-tuned mechanism that allows a gradual response to perceived stress. The T6SS/HmuR-mediated active zinc transport system is also involved in bacterial virulence and contact-independent bacterial competition. We describe a sophisticated bacterial zinc acquisition mechanism affording insights into the role of metal ion transport systems

Type VI Secretion System Transports Zn²⁺ to Combat Multiple Stresses and Host Immunity

<div><p>Type VI secretion systems (T6SSs) are widespread multi-component machineries that translocate effectors into either eukaryotic or prokaryotic cells, for virulence or for interbacterial competition. Herein, we report that the T6SS-4 from <i>Yersinia pseudotuberculosis</i> displays an unexpected function in the transportation of Zn²⁺ to combat diverse stresses and host immunity. Environmental insults such as oxidative stress induce the expression of T6SS-4 via OxyR, the transcriptional factor that also regulates many oxidative response genes. Zinc transportation is achieved by T6SS-4-mediated translocation of a novel Zn²⁺-binding protein substrate YezP (YPK_3549), which has the capacity to rescue the sensitivity to oxidative stress exhibited by T6SS-4 mutants when added to extracellular milieu. Disruption of the classic zinc transporter ZnuABC together with T6SS-4 or <i>yezP</i> results in mutants that almost completely lost virulence against mice, further highlighting the importance of T6SS-4 in resistance to host immunity. These results assigned an unconventional role to T6SSs, which will lay the foundation for studying novel mechanisms of metal ion uptake by bacteria and the role of this process in their resistance to host immunity and survival in harmful environments.</p></div

The activity of YezP in <i>Yptb</i> resistance to stresses.

<p><b>A.</b> The rescue of the <i>yezP</i> mutant or a T6SS-4 mutant by recombinant YezP. 0.05 μM recombinant YezP or YezP_H76A was added to bacterial survival experiments before viability assessment. Mutants complemented with the corresponding gene were used as controls. Note the partial activity of YezP_H76A. <b>B</b>. Deletion of <i>yezP</i> led to accumulation of intracellular ROS. Analysis of the mutants was performed as described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005020#ppat.1005020.g003" target="_blank">Fig 3</a> with the indicated fluorescence dyes. <b>C</b>. Recombinant YezP rescued the inhibition effects of a zinc chelator. TPEN and the indicated amounts of YezP or Zn^<b>2+</b> were incubated with bacterial cells prior to survival determination. <b>D</b>. <i>yezP</i> is required for the resistance to distinct cellular insults by <i>Yptb</i>. Bacteria were subjected to treatment with the indicated agents or conditions before determining bacterial survival rates. Gm, gentamicin. Data shown were the average of three independent experiments; error bars indicate SD from three independent experiments. ***, <i>p</i><0.001; **, <i>p</i><0.01; n.s., not significant.</p

Model of T6SS-4-facilitated Zn²⁺ transportation and oxidative resistance in <i>Yptb</i>.

<p>OxyR activated by oxidative signals binds to the operator in the promoter of T6SS-4 to activate the expression of the system and its substrate YezP, leading to the production and assembly of the system, which translocates YezP into the extracellular milieu. YezP form a complex with Zn^<b>2+</b> to deliver the ions into the cell via a yet unknown mechanism. Intracellular Zn^<b>2+</b> mitigates the hydroxyl radicals or potentially other cell damaging processes to make the cells resistant to diverse environmental challenges.</p

T6SS-4 is important for the accumulation of intracellular Zn²⁺ under oxidative stress conditions.

<p><b>A.</b> Zn^<b>2+</b> uptake by relevant <i>Yptb</i> strains. Mid-exponential phase of <i>Yptb</i> strains were exposed to 1.5 mM H₂O₂ for 20 or 30 min in PBS containing 1 μM ZnCl₂. Zn^<b>2+</b> associated with bacterial cells was measured by inductively coupled plasmon resonance atomic absorption spectrometry (ICP-MS). <b>B</b>. The alleviation of the sensitivity of <i>Yptb</i> mutants to H₂O₂ by exogenous Zn^<b>2+</b> required T6SS-4. <i>znuCB</i>, the canonical Zn^<b>2+</b> transporter; note that <i>clpV4M</i>, a mutant of <i>clpV4</i> defective in ATPase activity failed to complement the mutation. <b>C</b>. T6SS-4 is required for maximal bacterial survival in stress created by distinct agents. Mid-exponential phase bacteria were exposed to indicated agents or treatment for 1 hour (42°C for 30 min) and their survival was determined. <b>D</b>. T6SS-4 expression is induced by low zinc conditions. Cells of relevant <i>Yptb</i> strains harboring <i>T6SS-4p</i>::<i>lacZ</i> were grown in YLB medium with 100 μΜ Zn^<b>2+</b>, 100 μΜ TPEN, 100 μΜ TPEN together with 100 μΜ Zn^<b>2+</b> (TPEN+1×Zn), or 100 μΜ TPEN together with 200 μΜ Zn^<b>2+</b> (TPEN+2×Zn), and the expression of the reporter was measured. Data shown were the average of three independent experiments; error bars indicate SD from three independent experiments. ***, <i>p</i><0.001; **, <i>p</i><0.01; *, p<0.05; n.s., not significant.</p