POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. We analyzed the mutational features of purified bone marrow plasma cells from 42 patients ...newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.
Oxygen evolution reaction (OER) is a pivotal reaction in many technologies for renewable energy, such as water splitting, metal–air batteries, and regenerative fuel cells. However, this reaction is ...known to be kinetically sluggish and proceeds at rather high overpotential due to the universal scaling relationship, namely, the adsorption energies of intermediates are linearly correlated and cannot be optimized simultaneously. Several approaches have been proposed to break the scaling relationship by introducing additional active sites; however, positive experimental results are still absent. Herein, a different solution is suggested on the basis of dynamic tridimensional adsorption of the OER intermediates at NiO/NiFe layered double hydroxide intersection, by which the adsorption energy of each intermediate can be adjusted independently, so as to bypass the scaling relationship and achieve high catalytic performance. Experimentally, the OER overpotential is reduced to ≈205 mV at current density of 30 mA cm−2, which represents the best performance achieved by state‐of‐the‐art OER catalysts.
The oxygen evolution reaction (OER), a key reaction for energy conversion and storage, is kinetically sluggish due to the limits of the scaling relationship. A strategy to bypass the scaling relationship through dynamic tridimensional adsorption of OER intermediates is reported, and OER overpotential is reduced to 205 mV at current density of 30 mA cm−2.
An Fe–N‐decorated hybrid material of carbon nanotubes (CNTs) grown in situ from porous carbon microblocks is designed and constructed. This material successfully combines the desirable merits for ...oxygen reduction reaction (ORR), such as highly active Fe–N species, good conductivity, large pore size, and sufficient surface area. These structural advantages give this low‐priced material an outstanding catalytic performance for ORR closely comparable with Pt/C of the same quantity.
Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act ...as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.
Exploiting high‐performance, robust, and cost‐effective electrocatalysts for the oxygen evolution reaction (OER) is crucial for electrochemical energy storage and conversion technologies. Engineering ...the interfacial structure of hybrid catalysts often induces synergistically enhanced electrocatalytic performance. Herein, a new strongly coupled heterogeneous catalyst with proper interfacial structures, i.e., CoO nanoclusters decorated on CoFe layered double hydroxides (LDHs) nanosheets, is prepared via a simple one‐step pulsed laser ablation in liquid method. Thorough spectroscopic characterizations reveal that strong chemical couplings at the hybrid interface trigger charge transfer from CoII in the oxide to FeIII in the LDHs through the interfacial FeOCo bond, leading to considerable amounts of high oxidation state CoIII sites present in the hybrid. Interestingly, the CoO/CoFe LDHs exhibit pronounced synergistic effects in electrocatalytic water oxidation, with substantially enhanced intrinsic catalytic activity and stability relative to both components. The hybrid catalyst achieves remarkably low OER overpotential and Tafel slope in alkaline medium, outperforming that of Ru/C and manifesting itself among the most active Co‐based OER catalysts.
A strongly coupled CoO/CoFe layered double hydroxides heterogeneous catalyst with proper interfacial structures is prepared via a one‐step laser ablation method. The strong chemical coupling at the hybrid interface triggers charge transfer through the interfacial FeOCo bond, resulting in abundant high oxidation state CoIII sites. The hybrid catalyst exhibits pronounced synergistic effects for the oxygen evolution reaction, with substantially enhanced intrinsic activity, turnover frequency, and stability.
This study aimed to determine long non‐coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) expression in pancreatic cancer and to explore the potential molecular actions of SNHG14 in ...mediating pancreatic cancer progression. Gene expression was detected by quantitative real‐time PCR. Cell proliferation, growth and invasion were detected by respective CCK‐8, colony formation, and transwell invasion assays. Protein levels were measured by Western blotting. Cell apoptosis and caspase‐3 activity were detected by flow cytometry and caspase‐3 activity assay. The link between miR‐613 and its targets was evaluated by luciferase reporter assay. In vivo tumour growth was evaluated using a xenograft model of nude mice. SNHG14 expression was up‐regulated in cancerous tissues from pancreatic cancer patients. High expression of SNHG14 was associated with poor tumour differentiation, advanced TNM stage and nodal metastasis. SNHG14 overexpression enhanced cell proliferative, growth and invasive abilities, and suppressed apoptotic rates and caspase‐3 activity in pancreatic cancer cells, while SNHG14 knockdown exerted opposite effects. Mechanistic studies revealed that miR‐613 was targeted by SNHG14, and Annexin A2 (ANXA2) was targeted and inversely regulated by miR‐613 in pancreatic cancer cells. In vivo studies showed that SNHG14 knockdown attenuated tumour growth. MiR‐613 was down‐regulated and ANXA2 was up‐regulated in the pancreatic cancer tissues, and SNHG14 expression levels were inversely correlated with miR‐613 expression levels and positively correlated with the ANXA2 mRNA expression levels. Collectively, our results suggest that SNHG14 potentiates pancreatic cancer progression through modulation of annexin A2 expression via acting as a competing endogenous RNA for miR‐613.
To achieve high performed zinc metal batteries, it is imperative to address the issues of dendrite growth and the side‐reactions occurring at the Zn anode, particularly when the batteries are ...operated at high current densities and high temperature. Herein, a flexible and dendrite‐free Zn metal anode (AgNPs@CC/Zn), which is prepared by inkjet printing silver nanoparticles on a 3D carbon matrix, is reported. Experimental observations and DFT calculation reveal that the Ag nanoparticles can work as heterometallic seeds for zinc deposition, and thus simultaneously improve the zincophilicity and thermal conductivity of the carbon matrix. This not only lowers the Zn nucleation overpotential and guides the uniform Zn nucleation but also promotes the reversible zinc stripping/plating via AgZn alloying/de‐alloying reactions. As a result, the AgNPs@CC/Zn anode presents low voltage hysteresis of 80 mV and superior cycling over 480 h at a high current density of 10 mA cm−2. The AgNPs@CC/Zn anode can enable full cells with exceptional cyclic stability and enhanced high‐temperature endurance. Furthermore, the foldable pouch cell using the AgNPs@CC/Zn anode exhibits high capacity retention regardless of different deformation status. This work demonstrates the promising potential of inkjet printing technology in developing 3D dendrite‐free zinc anode for foldable and heat‐resistant zinc batteries.
A flexible and dendrite‐free Zn metal anode is prepared by inkjet printing silver nanoparticles on a 3D carbon matrix, boosting electrochemical performance of zinc metal batteries. The Ag nanoparticles as heterometallic seeds can promote reversible zinc stripping/plating via AgZn alloying/de‐alloying reactions and improve the zincophilicity and thermal conductivity of the carbon matrix.
Geopolymer (also called inorganic polymers) is a kind of amorphous gel material with a 3D structure consisting of SiO4 and AlO4 tetrahedra. It has drawn international attention due to its ...environmental friendliness and excellent performance. This review covers raw materials, preparation methods, and applications of porous geopolymer materials with micropore, mesopore, or macropore. The preparation methods can be divided into five categories: (i) self‐forming method, (ii) direct foaming method, (iii) adding filler method, (iv) particles stacking method, and (v) other methods. In this paper, different raw materials and applications were combined with the preparation methods, and some general conclusions of porous geopolymer were summarized. The applications of porous geopolymer materials in building materials, adsorbents, porous ceramics, membrane separation, catalyst, pH regulator, and other fields were introduced as well.
Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for ...upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.
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•Phosphorylation of NLRP3 at S194 is a key priming event for inflammasome activation•JNK1 directly phosphorylates NLRP3•S194 phosphorylation facilitates the self-association of NLRP3•Inhibiting NLRP3 phosphorylation could be a treatment for NLRP3-related diseases
The NLRP3 inflammasome activation requires a priming process; however, the mechanism remains obscure. Song et al. demonstrate that JNK1-mediated NLRP3 phosphorylation is a key molecular priming event that poises NLRP3 for its self-association and inflammasome assembly. This study suggests that inhibiting NLRP3 phosphorylation could be utilized in treating NLRP3-related diseases.
Oxidative stress contributes to the development of cardiac hypertrophy and heart failure. One of the mitochondrial sirtuins, Sirt4, is highly expressed in the heart, but its function remains unknown. ...The aim of the present study was to investigate the role of Sirt4 in the pathogenesis of pathological cardiac hypertrophy and the molecular mechanism by which Sirt4 regulates mitochondrial oxidative stress.
Male C57BL/6 Sirt4 knockout mice, transgenic (Tg) mice exhibiting cardiac-specific overexpression of Sirt4 (Sirt4-Tg) and their respective controls were treated with angiotensin II (Ang II, 1.1 mg/kg/day). At 4 weeks, hypertrophic growth of cardiomyocytes, fibrosis and cardiac function were analysed. Sirt4 deficiency conferred resistance to Ang II infusion by significantly suppressing hypertrophic growth, and the deposition of fibrosis. In Sirt4-Tg mice, aggravated hypertrophy and reduced cardiac function were observed compared with non-Tg mice following Ang II treatment. Mechanistically, Sirt4 inhibited the binding of manganese superoxide dismutase (MnSOD) to Sirt3, another member of the mitochondrial sirtuins, and increased MnSOD acetylation levels to reduce its activity, resulting in elevated reactive oxygen species (ROS) accumulation upon Ang II stimulation. Furthermore, inhibition of ROS with manganese 5, 10, 15, 20-tetrakis-(4-benzoic acid) porphyrin, a mimetic of SOD, blocked the Sirt4-mediated aggravation of the hypertrophic response in Ang II-treated Sirt4-Tg mice.
Sirt4 promotes hypertrophic growth, the generation of fibrosis and cardiac dysfunction by increasing ROS levels upon pathological stimulation. These findings reveal a role of Sirt4 in pathological cardiac hypertrophy, providing a new potential therapeutic strategy for this disease.
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