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Objective β2-Adrenoceptor agonists are widely used to treat asthma because of their bronchial-dilation effects. We previously reported that isoprenaline, via the apical and basolateral β2-adrenoceptor, induced Cl− secretion by activating cyclic AMP (cAMP)-dependent pathways in human bronchial epithelia. Despite these results, whether and how the β2-adrenoceptor-mediated cAMP-dependent pathway contributes to pro-inflammatory cytokine release in human bronchial epithelia remains poorly understood. Methods We investigated β2-adrenoceptor-mediated signaling pathways involved in the production of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, in 16HBE14o- human bronchial epithelia. The effects of isoprenaline or formoterol were assessed in the presence of protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC), Src, and extracellular signal-regulated protein kinase (ERK)1/2 inhibitors. The involvement of β-arrestin2 was examined using siRNA knockdown. Results Isoprenaline and formoterol (both β2 agonists) induced IL-6, but not IL-8, release, which could be inhibited by ICI 118,551 (β2 antagonist). The PKA-specific inhibitor, H89, partially inhibited IL-6 release. Another intracellular cAMP receptor, EPAC, was not involved in IL-6 release. Isoprenaline-mediated IL-6 secretion was attenuated by dasatinib, a Src inhibitor, and PD98059, an ERK1/2 inhibitor. Isoprenaline treatment also led to ERK1/2 phosphorylation. In addition, knockdown of β-arrestin2 by siRNA specifically suppressed cytokine release when a high concentration of isoprenaline (1 mM) was used. Conclusion Our results suggest that activation of the β2-adrenoceptor in 16HBE14o- cells stimulated the PKA/Src/ERK1/2 and/or β-arrestin2 signaling pathways, leading to IL-6 release. Therefore, our data reveal that β2-adrenoceptor signaling plays a role in the immune regulation of human airway epithelia.

This article introduces a clean and efficient method for the synthesis of Ti-MWW by utilizing the recycled mother liquor. The effects of titanium and silicon sources on the synthesis of Ti-MWW and the recycling of the mother liquor are discussed in detail. Precipitated silica prepared with Na2SiO3 and CO2 was selected as the silicon source, and TiCl3 was selected as the titanium source. The mother liquor was recycled five times, and the obtained samples showed good catalytic activity in cyclohexanone ammoximation. This work can be conducive to reducing the influence on the environment and economizing on materials for the industrial production of Ti-MWW.

To prepare supported catalysts with high loading and high dispersion of active metals is a crucial challenge in heterogeneous catalysis. Here we report the fabrication of very reactive catalyst that contains finely dispersed copper with 20 wt% content supported on high-surface area CeO2 for the water–gas shift (WGS) reaction. This copper-ceria catalyst shows superb activity with a CO consumption rate of 116.7 μmolCO gcat-1 s−1 at 300 ℃, nearly one order of magnitude more active than other copper-based catalysts ever reported. Based on the precise and integrated characterizations, the oxidized not the metallic Cu are proved to be active centers where the adsorbed CO directly reacted with bridged —OH groups to finish the WGS reaction. The oxidized Cu sites are confirmed to be originated from the activation effect from Cu to CeO2, which promotes the oxygen of CeO2 diffuse from the bulk to surface, making Cu oxidized even under reductive atmosphere.

A study of magnesia refractories containing glucose, citric acid, and metallic Al and their influences on structure, mechanical strength, and thermal shock resistance, is presented. Combined with thermodynamic calculation, microstructure, and properties analysis, the results show that formation of gluconates and citrates from the introduced glucose and citric acid enhanced the bonding of raw materials and the curing strength of samples. The pyrolysis of gluconates and citrates, and the oxidation and nitridation of metallic Al had significant effects on the microstructural evolution of magnesia refractories after high temperature treatments, mainly AlN and MgAl2O4 whiskers in pores and particle gaps. The formation and development of whiskers give rise to samples improved toughness and thermal shock resistance. Increasing the metallic Al content from 0 wt% to 2 wt% enhanced the fracture surface energy of samples heat treated at 1400 °C from 82.22 kJ/m2 to 119.75 kJ/m2. Meanwhile, after three thermal-shock cycles, the residual strength ratios of heat treated samples were elevated from 52.8% to 67.9%. On the basis of influences of phase transformation on the structure and properties of samples at different temperatures, considering the structural compactness and ability to withstand external stress for magnesia refractories used in metallurgical field, it is suggested that when glucose and citric acid are used as binders, the addition of metallic Al should be less than 3 wt%.

Symmetrical solid oxide fuel cells (SSOFCs) could be alternative energy conversion devices due to their simple fabrication process and low cost. Herein, perovskite La0.6Ce0.1Sr0.3Fe0.95Ru0.05O3–δ (LCSFR) was synthesized and evaluated as a high-performance electrode for SSOFCs based on the electrolyte of La0.9Sr0.1Ga0.8Mg0.2O3–δ (LSGM). LCSFR retains their stable perovskite crystal structure in both reducing and oxidizing atmospheres, though a minor amount of LaSrFeO4 phase is present under reducing conditions. Morphology investigation shows that homogeneously dispersed Ru metallic nanoparticles are exsolved on the surface of LCSFR after being reduced. The polarization resistance (Rp) of LCSFR-CGO (Ce0.9Gd0.1O2–δ) is about 0.11 Ω⋅cm2 at 800 °C in air, while the value of Rp for LCSFR-CGO in wet H2 (3% H2O) increases up to 0.32 Ω⋅cm2. The symmetrical LCSFR-CGO|LSGM|LCSFR-CGO cell demonstrates a performance with an open circuit potential (OCV) of 1.07 V and a maximum peak power density of 904 mW/cm2 at 800 °C using wet H2 as the fuel. This high performance indicates that LCSFR is a candidate electrode for SSOFCs.

Introduction The development of pancreatic ductal adenocarcinoma (PDAC) is closely tied with the immune system. C‐C motif chemokine ligands (CCL) were proved to lead to immune recruitment and training. Thus, we reckoned CCL2 to be the kernel of immune suppression in PDAC tissues. Methods We compared normal pancreatic tissues with PDAC tissues according to The Cancer Genome Atlas (TCGA) and clinical samples. Flow cytometry was used to identify M‐MDSCs. We further demonstrated immune suppression of M‐MDSCs according to proliferation rates of CD8+ T cells/CD4+ T cells. Levels of reactive oxygen species (ROS) and Arginase were also tested by flow cytometry, enzyme‐linked immunosorbent assay, and western blot analysis. We also analyzed the specific mechanisms by cluster analysis after CCL2 stimulating M‐MDSCs. Results We found that CCL2 highly increased in PDAC tissues. CCL2 is positively related to CD33 and CD14, markers of monocytic myeloid‐derived suppressor cells (M‐MDSCs). We have demonstrated that CCL2 recruited M‐MDSCs into PDAC tissues both in vitro and in vivo. M‐MDSCs recruitment is accompanied by sustained immune suppression. Furthermore, we have found that M‐MDSCs impeded T cell proliferation and produced high levels of ROS and Arginase, which can be enhanced by CCL2. Mechanistically, CCL2 stimulated M‐MDSCs led to a significant upregulation of genes, a large part of which accumulated in the mitogen‐activated protein kinase signaling pathway. Treatment of aloesin, MAPK signaling inhibitor, relieved the associated immunosuppressive phenotype induced by CCL2. Conclusions Our study indicates that PDAC cells produced CCL2, which promoted localized M‐MDSC recruitment and immune suppression, thereby promoting tumor progression., Our data indicate that CCL2 performs a significant role in PDAC progression by recruiting and activating M‐MDSCs. Targeting MDSCs is able to improve antitumoral immunological responses providing with potential applicability of immune‐based combination therapies against an extensive spectrum of solid tumors. These miscellaneous approaches might prove available for tumor therapeutics against solid carcinomas in which M‐MDSCs perform a major role in immune evasion of tumors. These results are promising and need further assessment of the M‐MDSCs‐targeting combination or vaccination approaches for the whole therapeutic capacity of these tactics in PDAC and other carcinomas, Highlights CCL2 is significantly upregulated in colon adenocarcinoma CCL2 influences M‐MDSC recruitment and functionality in colon adenocarcinoma CCL2 stimulates immune‐suppressive functions of M‐MDSC by activating MAPK signaling

Emerging evidence suggests that KIF11 could play a pivotal role in cancer cell proliferation; however, its biological functions and molecular mechanisms in Wilms tumor (WT) cells are largely unknown. The aim of this study was to evaluate the clinical significance and therapeutic potential of KIF11 proteins in WT. KIF11 expression in WT tissues and adjacent nontumor tissues was determined using qRT-PCR, Western blotting, immunohistochemistry (IHC) and bioinformatics. The function of KIF11 protein was determined by its correlation with tumor cell growth, angiogenesis, and apoptosis using IHC and lentiviral vector-mediated KIF11 depletion. KIF11 expression was upregulated in WT tissues and was associated with WT clinical outcomes. Tumor KIF11 expression was significantly associated with the Ki67 proliferation index. CCK-8, flow-cytometric analysis, and Western blotting revealed that KIF11 knockdown significantly inhibited WT cell growth. Functional studies have indicated that increased KIF11 expression is significantly correlated with vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density. We further confirmed that downregulated expression of KIF11 promoted cell apoptosis and significantly increased Bcl-2 and Bax expression. Our findings demonstrate that KIF11 plays a role in promoting the development of human WT and can serve as a potential molecular marker for the treatment of WT.

The over use of synthetic nitrogen (N) fertilizers is the major anthropogenic cause of low N-use efficiency and environmental damage in wetland rice production. Biochar (B) addition to soil is suggested as a climate change mitigation tool that supports carbon sequestration and reduces N losses and greenhouse gas emissions from the soil. Therefore, this study assessed the effect of four levels of B (0, 10, 20 and 30 t ha−1) combined with two levels of N (135 and 180 kg ha−1) on soil health, roots dynamics, physiological attributes, and yield components of rice. The addition of B at 30 t ha−1 combined with 135 N kg ha−1 increased chlorophyll content, net photosynthetic rate, biomass, and grain yield by 104%, 64%, 12%, and 30%, respectively, over control. Further, root traits such as total root length (TRL), total root volume (TRV), total root surface area (TRSA), and total average root diameter (TARD) were improved under 30 t ha−1 combined with 135 N kg ha−1 by 20%, 13%, 13%, and 25%, respectively, than non-biochar treatment under lower N application. Improvements in these traits resulted from higher N uptake due to improved soil physiochemical properties and soil microbial biomass combined with biochar. Interestingly, enhanced N metabolizing enzyme activities, including nitrate reductase (NR), glutamine synthetase (GS), and glutamine oxoglutarate aminotransferase (GOGAT) in biochar-treated plots, further supported the increases in these traits. Our results revealed that the integration of 30 t B ha−1 with 135 kg N ha−1 is a favorable option for enhancing soil health and rice grain yield.

Varying transport potential of cationic, zwitterionic, and anionic per- and polyfluoroalkyl substances (PFASs) may pose challenges for remediation of aqueous film forming foam (AFFF) impacted sites, particularly during groundwater extraction. Slow desorption of stronger sorbing, zwitterionic, and cationic PFASs may cause extended remediation times and rebound in aqueous PFAS concentrations. Persulfate oxidation has the potential to convert a complex mixture of PFASs into a simpler and more recoverable mixture of perfluoroalkyl acids (PFAAs). AFFF-impacted soils were treated with heat-activated persulfate in batch reactors and subjected to 7-day leaching experiments. Soil and water were analyzed using a combination of targeted and high resolution liquid chromatography mass spectrometry techniques as well as the total oxidizable precursors assay. Following oxidation, total PFAS composition showed the expected shift to a higher fraction of PFAAs, and this led to higher total PFAS leaching in pretreated reactors (108-110%) vs control reactors (62-90%). In both pretreated and control soils, precursors that remained following leaching experiments were 61-100% cationic and zwitterionic. Results suggest that persulfate pretreatment of soils has promise as an enhanced recovery technique for remediation of total PFASs in impacted soils. They also demonstrate that PFAS distribution may have been altered at sites where in situ chemical oxidation was applied to treat co-occurring contaminants of concern.

Graphical abstract, Leaf nitrogen (N) concentration plays an important role in biochemical and physiological functions, and N availability directly influences rice yield. However, excessive N fertilization is considered to be a root cause of environmental issues and low nitrogen use efficiency. Therefore, the selection of appropriate nutrient management practices and organic amendments is key to maximizing nitrogen uptake and maintaining high and sustainable rice production. Here, we evaluated the effects of different 15N-labelled nitrogen sources (urea, ammonium nitrate, and ammonium sulfate at 315 kg ha−1) with or without biochar (30 t ha−1) on paddy soil properties, root growth, leaf gas exchange, N metabolism enzymes, and N uptake in the early and late seasons of 2019. We found significant differences among N fertilizer sources applied with or without biochar (P

Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D–E (1–2), as well as eight known ones (3–10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and electronic circular dichroism (ECD) experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory activities on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activities with their IC50 values of 47.7 and 21.9 μM, compared to a positive control quercetin with the IC50 value of 16.0 μM.

The synthesis of a TS-1 zeolite with high-content framework Ti and small particles has been developed by adding NH4HCO3 and suspended seeds as an assistant. With the addition of NH4HCO3, the Hofmann decomposition of the tetrapropylammonium cation (TPA+) decreased, and the framework Ti content of the zeolite increased first and then decreased while the particle became larger. With the assistance of suspended seeds, the TS-1 synthesized under a low-alkalinity system possesses small particle size and high-content framework Ti, and it shows the best catalytic activity among the prepared catalysts. Because the decomposition of TPA+ decreased, the mother liquid could be reused in the next run of preparation. Even though the recycled mother liquid was reused five times, all obtained TS-1 samples exhibited similar catalytic performances in propylene epoxidation. This work provides an efficient process for preparing TS-1 with good catalytic performance and reduces the discharge of the waste liquid.

Despite advances in screening and treatment, colon cancer remains one of the leading causes of cancer-related death. Finding novel and useful drug treatment targets is also an urgent need for clinical applications. Tetrandrine (Tet) is extracted from the Chinese medicinal herbal medicine, which is a well-known calcium blocker with a variety of pharmacological activities, including anti-cancer. In this study, we recruited cell viability assay, flow cytometry analysis, cloning formation to confirm that Tet can inhibit the proliferation of SW620 cells, and induce apoptosis. Mechanically, we confirmed that Tet up-regulates the mRNA and protein level of BMP9 in SW620 cells. Over-expression BMP9 enhances the anti-cancer effects of Tet in SW620 cells, but these effects can be partly reversed by silencing BMP9. Also, Tet reduces phosphorylation of Aktl/2/3 in SW620 cells, which could be elevated by overexpressed BMP9 and impaired by silencing BMP9. Furthermore, we demonstrated that Tet reduces phosphorylated PTEN, which can be promoted by overexpressed BMP9, analogously also be attenuated through silencing BMP9. Finally, we introduced a xenograft tumor model to investigate the anti-proliferative effect of Tet, further to explore the effects of BMP9 and PTEN in SW620 cells. Our findings suggested that the anti-cancer activity of Tet in SW620 cells may be mediated partly by up-regulating BMP9, followed by inactivation PI3K/Akt through up-regulating PTEN at least.

After completing the thio-substitution with Lawesson’s reagent, ethanol was found to be effective in the decomposition of the inherent stoichiometric six-membered-ring byproduct from the Lawesson’s reagent to a highly polarized diethyl thiophosphonate. The treatment significantly simplified the following chromatography purification of the desired thioamide in a small scale preparation. As scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not generate P-containing aqueous waste, and only organic effluents were discharged. It is believed that the optimized procedure offers the great opportunity of applying the Lawesson’s reagent for various thio-substitution reactions on a large scale.

The dissemination of circulating tumor cells (CTCs) in peripheral blood is an important intermediate step for cancer metastasis. It has become one of the most promising targets of “liquid biopsy”, on account of providing complete information of cell biology. However, due to the extremely rarity, complex environment and strong heterogeneity of CTC in peripheral blood, the development of efficient enrichment and separation methods are the key in the accurate detection of CTC. Currently reported CTC enrichment and analysis techniques are mainly based on the physical or biological characteristics of CTC. They are commonly combined with the traditional techniques including density gradient centrifugation, superfine membrane filtration and immunomagnetic separation, the novel methods such as microfluidic chip separation and two-dimensional electrophoresis-field separation, and the analysis techniques such as reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, photoacoustic imaging, surface-enhancement Raman scattering and electrochemistry to realize accurate detection of CTC. In this review, we summarized the recent processes on enrichment and novel detection methods of CTC and discussed the challenges and their clinical application status, which could provide reference for the further improvement of the technology of enrichment, accurate counting and molecular phenotype analysis for CTC, as well as the application in scientific research and clinical practice.

Recently, there are significant progresses in the growth of organic-inorganic lead halide perovskite single crystals, however, due to their susceptible nucleation and growth mechanisms and solvent requirements, the efficient and generalized growth for these single crystals is still challenging. Here we report the work towards this target with a polymer-controlled nucleation process for the highly efficient growth of large-size high-quality simple ternary, mixed-cations and mixed-halide perovskite single crystals. Among them, the carrier lifetime of FAPbBr3 single crystals is largely improved to 10199 ns. Mixed MA/FAPbBr3 single crystals are synthesized. The crucial point in this process is suggested to be an appropriate coordinative interaction between polymer oxygen groups and Pb2+, greatly decreasing the nuclei concentrations by as much as 4 orders of magnitudes. This polymer-controlled route would help optimizing the solution-based OIHPs crystal growth and promoting applications of perovskite single crystals., Research into single crystal organic-inorganic halide perovskites have gained momentum due to the potential applications, yet the growth is still a challenge. Here, the authors demonstrate a universal method based on polymer controlled nucleation process to achieve large-size and high-quality perovskite single crystals.

A series of novel indole-1,2,4-triazole derivatives have been designed, synthesized, and evaluated as potential tubulin polymerization inhibitors. The top hit 12, bearing the 3,4,5-trimethoxyphenyl moiety, exhibited substantial anti-proliferative activity against HepG2, HeLa, MCF-7, and A549 cells in vitro with IC50 values of 0.23 ± 0.08 μM, 0.15 ± 0.18 μM, 0.38 ± 0.12 μM, and 0.30 ± 0.13 μM, respectively. It also inhibited tubulin polymerization with the IC50 value of 2.1 ± 0.12 μM, which was comparable with that of the positive controls. Furthermore, compound 12 regulated the expression of cell cycle-related proteins (Cyclin B1, Cdc25c, and Cdc2) and apoptosis-related proteins (Bcl-2, Bcl-x, and Mcl-1). Mechanistically, compound 12 could arrest cell cycle at the G2/M phase, thus induce an increase of apoptotic cell death. In addition, molecular docking hinted the possible interaction mode of compound 12 into the colchicine binding site of tubulin heterodimers. According to the applications of microtubule-targeting agents in both direct and synergistic cancer therapies, we hope this work might be of significance for future researches.

Background: : The appearance of antibiotic resistance caused by metallo-β-lactamases (MβLs) is a global public health threat. Developing MβLs inhibitor is an effective way to overcome antibiotic resistance. Recently, azolylthioacetamides were reported to be promising MβLs inhibitors. Methods:: Triazolylthioacetamides were synthesized and tested for inhibition activity against the purified MβL IMP-1. Antimicrobial activities of these inhibitors in combination with cefazolin were evaluated. Isothermal Titration Calorimetry (ITC) was employed to characterize the binding of the inhibitor to IMP-1, and their action mechanism was studied by molecular docking. Results: Twenty compounds exhibited specific inhibitory activity against IMP-1 with an IC50 value in the range of 3.1-62.5 μM. Eight of the compounds can restore the antibacterial efficacy of cefazolin against E. coli BL21 strain producing IMP-1 by 2-4 fold. ITC monitoring showed that 1c exhibited dose-dependent inhibition on IMP-1. Docking studies revealed that the triazole group in 1c and 2d played an essential role in the inhibition activity. Cytotoxicity assay showed that 1c and 2d have low toxicity in L929 mouse fibroblastic cells. Conclusion: : The triazolylthioacetamides are efficient inhibitors of IMP-1 in vitro and in vivo.

Improving grain filling in the presernt farming systems is crucial where grain filling is a concern due to the extreme use of chemical fertilizers (CF). A field experiment was conducted at the experimental station of Guangxi University, China in 2019 to test the hypothesis that cattle manure (CM) and poultry manure (PM) combined with CF could improve rice grain filling rate, yield, biochemical and qualitative attributes. A total of six treatments, i.e., no fertilizer (T1), 100% CF (T2), 60% CM + 40% CF (T3), 30% CM + 70% CF (T4), 60% PM + 40% CF (T5), and 30% PM + 70% CF (T6) were used in this study. Results showed that the combined treatment T6increased starch metabolizing enzymes activity (SMEs), such as ADP-glucose phosphorylase (ADGPase) by 8 and 12%, soluble starch synthase (SSS) by 7 and 10%, granule bound starch synthesis (GBSS) by 7 and 9%, and starch branching enzyme (SBE) by 14 and 21% in the early and late seasons, respectively, compared with T2. Similarly, higher rice grain yield, grain filling rate, starch, and amylose content were also recorded in combined treatments. In terms of seasons, higher activity of SMEs , grain starch, and amylose content was noted in the late-season compared to the early season. The increment in these traits was mainly attributed to a lower temperature in the late season during the grain filling period. Furthermore, our results suggested that an increment in starch accumulation and grain filling rate were mainly associated with the enhanced sink capacity by regulating key enzyme activities involved in Suc-to-starch conversion. In-addition, RT-qPCR analysis showed higher expression levels of AGPS2b, SSS1, GBSS1, and GBSE11b genes, which resultantly increased the activities of SMEs during the grain filling period under combined treatments. Linear regression analysis revealed that the activity of ADGPase, SSS, GBSS, and SBE were highly positively correlated with starch and amylose accumulation. Thus, we concluded that a combination of 30% N from PM or CM with 70% N from CF is a promising option in terms of improving rice grain yield and quality. Our study provides a sustainable fertilizer management strategy to enhance rice grain yield and quality at the lowest environmental cost.

Fibrous perovskite oxide has been the most promising cathode for intermediate-temperature solid oxide fuel cells (IT-SOFCs) due to its efficient mass and charge transfer. Herein, a core–shell fiber...

A nickel-catalyzed reductive decyanation of aromatic nitriles has been developed, in which the readily available and abundant ethanol was applied as the hydride donor. Various functional groups on the aromatic rings, such as alkoxyl, amino, imino and amide, were compatible in this catalytic protocol. Heteroaryl, benzylic and alkenyl nitriles were also tolerated. Mechanistic investigation indicated that ethanol provided hydride efficiently via β-hydride elimination in this reductive decyanation.

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin–actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics via pharmacologically targeting molecular motor. Here, we found J13 could directly target myosin-9 (MYH9)–actin molecular motor to promote mitochondrial fission progression, and markedly inhibited cancer cells survival, proliferation and migration. Mechanism study revealed that J13 impaired MYH9–actin interaction to inactivate molecular motor, and caused a cytoskeleton-dependent mitochondrial dynamics imbalance. Moreover, stable isotope labeling with amino acids in cell culture (SILAC) technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9–actin molecular motor to mitochondrial fission. Taken together, we reported the first natural small-molecule directly targeting MYH9–actin molecular motor for anti-cancer translational research. Besides, our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy., Graphical abstract Natural-derived small-molecule J13 restrained the interaction between myosin-9 (MYH9) and actin molecular motor via prompting heat-shock protein A9 (HSPA9) attached to MYH9, resulting in excessive mitochondrial fission with implications for human cancer therapy.Image 1

The drug resistance caused due to the overuse of antibiotics has grown into an emerging threat. It is urgent to develop novel strategies to combat bacterial resistance. In this work, a quinine-based quaternized polymer with amphiphilicity (QMTA) was prepared by free-radical copolymerization of quinine and (2-methacryloyloxyethyl) trimethyl ammonium chloride (MTA). Biological activity assays revealed that the polymer sterilized the drug-resistant Gram-negative E. coli and non-resistant Gram-positive bacteria B. subtilis, exhibiting a MIC value of 2 μg mL−1 and a bactericidal rate of more than 95%. Most importantly, both E. coli and B. subtilis treated with the polymer didn't develop resistance even after their 16th passages. Also, the polymer has low toxicity at a dose of up to 128 μg mL−1. The mechanism studies through SEM and 3D-SIM images, fluorescence staining and membrane potential determination reveal that the positively charged QMTA initially concentrates on the surface of bacteria by electrostatic adsorption, changes the membrane potential, binds to the bacteria by its quinine chain, and destroys the membrane structure of the bacteria. This study provides a potential approach through the existing drug to develop new bactericidal reagent/polymer materials without resistance.

Vinyl methyl ether (VME) is an important chemical intermediate for the production of functional polymers and fine chemicals. It is primarily produced in industry via the addition of methanol to acetylene, known as Reppe vinylation. However, the requirement for high pressures and caustic bases as catalysts limits its practical applications. Here, we report a novel route for the sustainable synthesis of VME from biomass-derived ethylene glycol dimethyl ether (EGDE) via the methanol elimination reaction catalyzed by CaO-based solid bases at atmospheric pressure. The co-precipitated CaO–MgO catalyst with a Ca/Mg molar ratio of 2 exhibited high efficiency and stability, achieving 100% EGDE conversion and 93.5% selectivity to VME at 400 °C. The strongly basic sites facilitated the formation of VME on the CaO–MgO surfaces, whereas, for comparison, the weakly basic sites on MgO or acidic sites on amphoteric oxides (e.g. CeO2) and solid acids (e.g. H-ZSM-5) were found to promote the degradation of VME. This work provides a viable and sustainable strategy for the synthesis of VME and other high-value vinyl compounds from biomass.

Continuous real-time measurement of body temperature using a wearable sensor is an essential part of human health monitoring. Electrospun aligned carbon nanofiber (ACNF) films are employed to assemble flexible temperature sensors. The temperature sensor prepared at a low carbonization temperature of 650 °C yields an outstanding sensitivity of 1.52% °C−1, high accuracy, good linearity, fast response time and excellent long-term durability. Moreover, it exhibits high discriminability towards temperature amidst other unwanted stimuli and maintains its original performance even after repeated stretch/release cycles because of highly-aligned structures. The correlation between the atomic structure and the temperature sensing performance of ACNF sensors is established. Contrary to conventional highly conductive temperature sensors, the ACNF sensor with a low electrical conductivity prepared at a low carbonization temperature ameliorates the temperature sensing performance. This anomaly is explained by (i) the smaller and more disordered sp2 carbon crystallites yielding a high negative temperature coefficient, (ii) a larger number of defects, and (iii) a higher pyridinic-N content generating abundant entrapped and localized electrons which are activated once sufficient thermal energy is available. Flexible ACNF sensor's overall performance is among the best-known carbon material-based flexible temperature sensors, demonstrating potential applications in emerging healthcare and flexible electronics technologies.

It is imperative to develop innovative and efficient antibacterial agents, on account of the mounting prevalence of complicated infections induced by multidrug-resistant bacteria. In this work, Chol-b-Lys nanoparticles (CL-NPs) with a diameter of 304.9 nm were prepared by ring-opening polymerization of the monomers cholesterol-ethylenediamine conjugate (Chol-NH2) and L-Lys-N-carboxyanhydrides (L-Lys-NCAs) and further self-assembly. The nanoparticles exhibited biological activity against the drug-resistant and non-resistant bacteria, including Gram-negative E. coli and Gram-positive B. subtilis, E. faecalis and S. aureus, with a MIC value in the range of 32–2 μg mL−1 and a more than 95% bactericidal rate. Importantly, both bacteria treated with CL-NPs didn’t develop resistance even after their 16th passages. Also, the CL-NPs have low toxicity (32 μg mL−1). The mechanism characterization shows that the positively charged nanoparticles are initially gathered on the surface of bacteria by electrostatic adsorption, changes the membrane permeability, inserts into the lipid bilayer bacteria membrane with cholesterol groups, destroys the membrane structure and results in bacterial apoptosis. This work provides a potential approach by mimicking the structure of cell membrane to develop new bactericidal reagent/nanoparticle materials which is hard to cause resistance.

The massive usage of electronic and telecommunication devices has led to serious concerns regarding undesired electromagnetic pollution. While metals such as silver, aluminum and copper are the mostly used materials to shield electromagnetic interference, organic conducting polymers are gaining momentum for lightweight, flexible and wearable systems. In this work, we used three dimensional (3D) sponges and hydrogel films based on the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) to demonstrate electromagnetic interference (EMI) shielding applications in the X-band frequency range (8–12.4 GHz). The 3D PEDOT:PSS sponges showed a porous structure composed of thread-like and sheet-like micro-features that offer an excellent electromechanical response under compressive strain, due to the collapse of micropores in the sponge structure. Interestingly, the compressive strain remarkably enhanced the shielding effectiveness (SE) value of PEDOT:PSS sponges from about 15 dB to 24 dB. PEDOT:PSS hydrogel films with a compact morphology showed a high SE value of about 105 dB. For both PEDOT:PSS sponges and hydrogel films, reflection and absorption processes contributed to the total SE.

Bone marrow mesenchymal stem cells (BMMSCs)-based therapy has emerged as a promising novel therapy for Traumatic Brain Injury (TBI). However, the therapeutic quantity of viable implanted BMMSCs necessary to initiate efficacy is still undetermined. Increased oxidative stress following TBI, which leads to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathway, has been implicated in accounting for the diminished graft survival and therapeutic effect. To prove this assertion, we silenced the expression of NADPH subunits (p22-phox, p47-phox, and p67-phox) and small GTPase Rac1 in BMMSCs using shRNA. Our results showed that silencing these proteins significantly reduced oxidative stress and cell death/apoptosis, and promoted implanted BMMSCs proliferation after TBI. The most significant result was however seen with Rac1 silencing, which demonstrated decreased expression of apoptotic proteins, enhanced in vitro survival ratio, reduction in TBI lesional volume and significant improvement in neurological function post shRac1-BMMSCs transplantation. Additionally, two RNA-seq hub genes (VEGFA and MMP-2) were identified to play critical roles in shRac1-mediated cell survival. In summary, we propose that knockdown of Rac1 gene could significantly boost cell survival and promote the recovery of neurological functions after BMMSCs transplantation in TBI mice.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.