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Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2–10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy. [Image: see text]

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.

Currently, supported copper-based catalysts have been regarded as one of the most promising catalysts for catalyzing the hydrogenation of CO2 to synthesize methanol, due to their good selectivity t...

Graphitic carbon nitride (g-C3N4) with unique physicochemical features has garnered much attention in artificial photosynthesis, yet the photoactivity of pristine g-C3N4 (PCN) is severely restricted because of its rapid charge recombination rate and narrow visible-light absorption. To this end, for the first time, here we reported a rational one-step copolymerization strategy for the fabrication of carbon self-doped g-C3N4 (CCN) by using melamine and chitosan as the starting materials. Experimental results indicated that the bridged N atoms were substituted by C atoms in the g-C3N4 matrix, resulting in the formation of delocalized big π bonds, thereby the obviously increased the electrical conductivity, remarkably extended the visible-light absorption region, and significantly improved the mobility of photoinduced electron-hole pairs. Consequently, the as-engineered CCN with abundant mesopores structure showed a dramatically boosting photocatalytic H2-evolved activity (1224 μmol g−1 h−1), 4.5-folds than PCN powders. Eventually, the resulting CCN exhibited an extremely long-term durable stability after storing in reaction solution for 90 days. Our work will bring about potential application in designing of high-performance g-C3N4 photocatalyst for renewable solar-to-H2 conversion.

The maintenance and expansion of cancer stem-like cells (CSCs) is necessary for metastasis. Although protease-activated receptor 2 (PAR2) is strongly associated with colorectal cancer (CRC) progression, it is unclear how it regulates distal metastasis, and no studies have shown the involvement of CSCs. In this study, we demonstrated that high PAR2 protein expression was correlated with metastatic CRC and poor prognosis in patients with stage III-IV CRC. CSCs from cell lines and patients showed higher levels of PAR2 than that of corresponding non-CSCs, and PAR2 inhibition reduced the CSC properties of the cell lines. Mechanistically, PAR2 inhibition switched the division mode of CSCs from symmetrical to asymmetrical via the ERK/GSK-3β/β-catenin pathway. We also identified periostin as a direct transcriptional target of β-catenin that mediates CSC self-renewal via PAR2 signaling. In a mouse xenograft model, PAR2 knockdown significantly attenuated liver metastasis. Finally, PAR2 expression was positively correlated with β-catenin and periostin in the primary sites of CRC with distant metastasis. Overall, our results indicate that PAR2 activation enhances CSC self-renewal and promotes metastasis through β-catenin and its target gene, periostin, in CRC.

In plants, NO has been proved the function of improving abiotic stress resistance. However, the role of NO in the lignin metabolism of okra under cold stress has not been clarified. Here, histochemical staining and lignin content analysis showed that cold stress promoted the lignin accumulation of cold stored okra pods, and NO inhibited the lignin accumulation and delayed lignification process. To better understand the roles of NO in okra cold stress resistance mechanism, the full-length transcriptome data of 'Hokkaido' was analyzed. The SNP-treated okra transcriptome and cPTIO-treated okra transcriptome were obtained. A total of 41957 unigenes were screened out from three groups at 10 d, among which, 33, 78 and 18 DEGs were found in ddH2O-treat, SNP-treat and cPTIO-treat group, respectively. Transcriptomic data suggested that the genes involved in lignin biosynthesis showed downregulation under SNP treatment. Transcriptomic data and enzyme activity showed that exogenous NO significantly promoted the biosynthesis of endogenous NO by enhancing NOS activity. Transcriptomic data and plant hormone data showed that NO played an important role in the process of inhibiting the ethylene and ABA synthesis mechanism of okra and thereby reducing the endogenous ethylene and ABA content under chilling stress. Relevant physiological data showed that NO helped to the protection of ROS scavenging system and removed the MDA and H2O2 induced by cold stress. These results provided a reference for studying the molecular mechanism of nitric oxide delaying the lignification of okra, and also provided a theoretical basis for postharvest storage of vegetables.

Amino acid-tuned self-assembly has become an attractive strategy for constructing various functional materials. Here, a series of dibenzocyclooctyne (DIBO) functionalized amphiphilic amino acid derivatives are designed and screened as building blocks of functional supramolecular self-assembly nanoparticles for cancer immunotherapy. One top-performing supramolecular self-assembly material (named DA6C1) is identified through combinatorial screening, and spherical nanoparticles can be easily prepared by this material tuned multicomponent synergistic self-assembly of ovalbumin (OVA) and CpG oligonucleotide. DA6C1 based nanovaccine can significantly enhance the cellular uptake of OVA and CpG into the same bone marrow derived dendritic cells (BMDCs) and greatly improve the activation of DCs. Moreover, after subcutaneous injection, this nanovaccine flows rapidly to the lymph nodes and elicits strong immune responses to achieve effective prophylactic and therapeutic effect. Therefore, our work highlights the great potential of clickable amino acid derivatives as a convenient and powerful tool to construct nanovaccine for effective immunotherapy.

Deoxynivalenol (DON) is synthesized by Fusarium species that frequently infect crops during storage, and it’s harm risk to human is reflected in the consumption of infected food crops or indirectly through foods of animal origin. In this study, Hela and Chang liver cells were used to research the cellular apoptosis induced by deoxynivalenol. Cells were treated by DON toxin with a series of concentration and incubated for different time. MTT, fluorescence microscope, flow cytometer and Western blot methods were used to analyze the effect of DON on the cell apoptosis in vitro and in vivo systematically. The results showed that DON was toxic to the cells tested. After being treated by DON, the morphology of Chang livers and Hela cells changed significantly. The DON promoted apoptosis in a dose- and time-dependent manner. The activity of Caspase 3 was significantly increased in DON-induced apoptosis. Moreover, endogenous Glutathione (GSH) level in these cell lines was gradually decreased. In the early apoptosis progress, oxidative stress was induced by DON. When DON reached 10 µg/mL, a markedly increased content of Malondialdehyde (MDA) was detected in both Hela and Chang liver cells. Furthermore, an in vivo test indicated that DON had toxicity to mice by causing weight loss and swollen spleen, and significantly increased expression of AST and ALT. In conclusion, the DON was toxic to mice and could induce the apoptosis of tested cells undergoing a Caspase-3 related pathway.

Objective: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis. Methods: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis. Results: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury. Conclusion: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

This study investigated the effect of polycaprolactone (PCL) loading (0.5, 1, and 3 wt%) on the morphology, tensile strength, and thermal properties of microcellular injection molded PP/PCL and PPgMA/PCL composites. We used the filler, PCL, that is micro-material in size. Results showed that 0.5 wt% loading of PCL on foamed PP has the largest tensile strength. However, tensile strength was almost similar to that of PPgMA composites. Tensile strength depends on the filler dispersion in the matrix and cell size present on the foamed composites. Good dispersion resulted in good tensile strength. The elongation decreased on PP but increased on PPgMA composites. The highest degradation temperature for PP/PCL and PPgMA/PCL was noted for 3.0 wt% PCL loading and neat PPgMA respectively. Cell size decreased and cell density increased with the addition of PCL into the PP and PPgMA matrix.

Currently, the CO2 conversion to light olefins is attractive in clean energy research. Despite numerous works on Co-Fe bimetallic catalysts, the lack of well-defined bulk structures with identical crystalline phase and similar textural property hinders the in-depth understanding of the roles of Fe and Co species. Herein, series of uniform K-containing spinel-type ZnCoxFe2-xO4 nanoparticles (x = 0, 0.5, 1.0, 1.5, 2.0) were successfully synthesized via a single source layered double hydroxide precursor route. Compared to ZnFe2O4 and ZnCo2O4, as-fabricated ternary ZnCo0.5Fe1.5O4 spinel nanoparticles as the catalyst exhibited an outstanding performance toward CO2 hydrogenation to produce light olefins, with a 36.1% selectivity toward C2=-C4= products at a 49.6% conversion and an unprecedentedly high iron time yield for CO2 conversion to light olefins (∼29.1 μmolCO2·gFe−1·s−1) at the gaseous hourly space velocity of 24000 mL·gcat−1·h−1. In combination with structural characterizations and reaction results, it was unveiled that during the CO2 hydrogenation over ternary ZnCoxFe2-xO4 catalysts, the formation of electron-rich Fe0 atoms in the CoFe alloy phase significantly promoted in situ the generation of active iron-cobalt carbide, Co2C, and θ-Fe3C phases, thereby improving the reactivity of catalysts for the production of hydrocarbons and simultaneously inhibiting both the CO2 methanation and the secondary hydrogenation of olefins. The present findings provide a clear understanding of the roles of Fe-Co interactions over ternary ZnCoxFe2-xO4 catalysts for the highly efficient hydrogenation of CO2 to produce light olefins.

An amino-modified multiwalled carbon nanotube (MWCNT) solid-phase extraction-based hydrophilic interaction liquid chromatography���tandem mass spectrometry (HILIC���MS/MS) method was developed for simultaneous determination of 13 paralytic shellfish toxins (PSTs) in bivalve mollusks. Shellfish samples were extracted with 1% acetic acid followed by cleanup using optimized MWCNT-NH2 based solid-phase extraction. Absorbed PSTs were eluted with 2 mL 1% acetic acid���acetonitrile (70/30, v/v). The separation was performed on a Waters BEH Amide column within 7.5 min utilizing 0.1% formic acid���acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase. The analytes were quantified by matrix-matched external standard curves with correlation coefficients�� exceeding 0.997 acquired in multiple reaction-monitoring mode. The limits of detection and quantitation in shellfish samples were from 2.76 to 9.8 ��g/kg and 9.11 to 39.3 ��g/kg, respectively. Recoveries at three spiked levels ranged from 71.4% to 97.8% with relative standard deviations less than 12.6%. The developed method was satisfactorily applied to the analysis of shellfish.

With the goal of constructing a carbon-free energy cycle, proton-exchange membrane (PEM) water electrolysis is a promising technology that can be integrated effectively with renewable energy resources to produce high-purity hydrogen. IrO2, as a commercial electrocatalyst for the anode side of a PEM water electrolyzer, can both overcome the high corrosion conditions and exhibit efficient catalytic performance. However, the high consumption of Ir species cannot meet the sustainable development and economic requirements of this technology. Accordingly, it is necessary to understand the OER catalytic mechanisms for Ir species, further designing new types of low-iridium catalysts with high activity and stability to replace IrO2. In this review, we first summarize the related catalytic mechanisms of the acidic oxygen evolution reaction (OER), and then provide general methods for measuring the catalytic performance of materials. Second, we present the structural evolution results of crystalline IrO2 and amorphous IrOx using in situ characterization techniques under catalytic conditions to understand the common catalytic characteristics of the materials and the possible factors affecting the structural evolution characteristics. Furthermore, we focus on three types of common low-iridium catalysts, including heteroatom-doped IrO2 (IrOx)-based catalysts, perovskite-type iridium-based catalysts, and pyrochlore-type iridium-based catalysts, and try to correlate the structural features with the intrinsic catalytic performance of materials. Finally, at the end of the review, we present the unresolved problems and challenges in this field in an attempt to develop effective strategies to further balance the catalytic activity and stability of materials under acidic OER catalytic conditions.

Currently, ischemic stroke is the leading cause of disability and death worldwide, and the performance of corresponding drugs is often unsatisfactory owing to the complex pathological processes and the impediment of the blood-brain barrier (BBB). Here, we employed various tertiary amino groups, including different linear, cyclic, and bimolecular drug structures, to modify 3-n-butylphthalide (NBP), a natural product used for ischemic stroke treatment, which has poor bioavailability, to generate a series of six prodrugs. These prodrugs showed significantly improved solubility and cellular uptake, which were primarily driven by putative pyrilamine cationic transporters. They also displayed more efficient brain delivery in vivo, reaching as high as 21.5-fold brain accumulation increase compared with NBP, leading to much higher bioavailability and stronger therapeutic effects. The toxicity of these molecules is also lower or similar to that of unmodified NBP. We showed that the tertiary amino group-modified NBP prodrugs are effective and safe for treating ischemic stroke with significantly enhanced druggability; hence, they have potential for further clinical development.

Summary The enzymatic conversion of l‐methionine (l‐Met) into volatile organic sulfur‐containing compounds (VOSCs) plays an important role in developing the characteristic aroma of foods. However, the mechanism for the direct conversion of l‐Met into VOSCs is still unclear in yeast cells used to make food products. Here, we show that the transcription profile of YALI0C22088g from Yarrowia lipolytica correlates positively with l‐Met addition. YALI0C22088g catalyses the γ‐elimination of l‐Met, directly converting l‐Met into VOSCs. YALI0C22088g also exhibits strong C‐S lysis activities towards l‐cystathionine and the other sulfur‐containing compounds and forms a distinct cystathionine‐γ‐lyase subgroup. We identified eight key amino acid residues in YALI0C22088g, and we inferred that the size of the tunnel and the charges carried by the entrance amino acid residue are the determinants for the enzymatic conversion of l‐Met into VOSCs. These findings reveal the formation mechanism of VOSCs produced directly from l‐Met via the demethiolation pathway in Yarrowia lipolytica, which provides a rationale for engineering the enzymatic conversion of l‐Met into VOSCs and thus stimulates the enzymatic production of aroma compounds., YALI0C22088g from Yarrowia lipolytica catalyses the γ‐elimination of l‐methionine, directly converting l‐methionine into VOSCs. YALI0C22088g also exhibits strong C‐S lysis activities toward the other sulfur‐containing compounds and forms a distinct cystathionine‐γ‐lyase subgroup. The size of the tunnel and the charges carried by the entrance amino acid residues are inferred to be the determinants for the enzymatic conversion of l‐Met into VOSCs.

Currently, the highly efficient conversion of biomass resources into highly valuable chemicals and biofuels is one of the most prospective approaches to reduce greenhouse gases emission and environmental pollution caused by excess consumption of fossil fuels. Herein, three-dimensional pompon-like well-defined RuCo particles with tunable crystallographic structures and surface atomically dispersed Ru atoms were constructed and intensively investigated as support-free metal catalysts in the hydrodeoxygenation (HDO) of lignin-derived guaiacol. It was demonstrated that the 300 °C-reduced RuCo sample possessed the hexagonal close-packed (hcp ) crystallographic structure with surface abundant atomically dispersed Ru atoms, whereas 600 °C-reduced RuCo sample presented the face-centered cubic phase with lower surface Ru concentration. The as-fabricated RuCo-300 sample showed excellent catalytic HDO activity with a high cyclohexane yield of 85.3%. Comprehensive structural characterizations unveiled that the introduction of atomically dispersed Ru atoms into the RuCo-300 favored the formation of abundant surface Ru-Co sites, as well as electron-rich Ru 0, and such-constructed Ru-Co sites were highly beneficial to the hydrogen dissociation on single Ru0 atoms and the further hydrogen spillover to adjacent Co0 atoms to promote the HDO process. Moreover, density functional theory (DFT) calculations revealed that the hcp structure of RuCo catalysts benefited the adsorption of guaiacol. The unique pompon-like microstructure of RuCo catalysts was conducive to the exposure of active sites and provided more open channels for the easy diffusion of reactants and products. Over the RuCo-300 catalyst, the guaiacol HDO could proceed rapidly via an initial demethoxylation reaction. The present Ru-Co synergetic catalysis in the structure of RuCo catalysts would provide a new strategy for constructing robust heterogeneous bimetal catalysts applied in practical HDO processes of a variety of lignin-derived phenolic compounds.

Background Endometritis is the most common disease of dairy cows and traditionally treated with antibiotics. Lactic acid bacteria can inhibit the growth of pathogens and also have potential for treatment of endometritis. Using PacBio single-molecule real-time sequencing technology, we sequenced the full-length l6S rRNA of the microbiota in uterine mucus samples from 31 cows with endometritis, treated with lactic acid bacteria (experimental [E] group) and antibiotics (control [C] group) separately. Microbiota profiles taken before and after treatment were compared. Results After both treatments, bacterial species richness was significantly higher than before, but there was no significant difference in bacterial diversity. Abundance of some bacteria increased after both lactic acid bacteria and antibiotic treatment: Lactobacillus helveticus, Lactococcus lactis, Lactococcus raffinolactis, Pseudomonas alcaligenes and Pseudomonas veronii. The bacterial species that significantly decreased in abundance varied depending on whether the cows had been treated with lactic acid bacteria or antibiotics. Abundance of Staphylococcus equorum and Treponema brennaborense increased after lactic acid bacteria treatment but decreased after antibiotic treatment. According to COG-based functional metagenomic predictions, 384 functional proteins were significantly differently expressed after treatment. E and C group protein expression pathways were significantly higher than before treatment (p Conclusions In this study, we found that lactic acid bacteria could cure endometritis and restore a normal physiological state, while avoiding the disadvantages of antibiotic treatment, such as the reductions in abundance of beneficial microbiota. This suggests that lactic acid bacteria treatment has potential as an alternative to antibiotics in the treatment of endometritis in cattle. How to cite: Yang L, Huang W, Yang C, et al. Using PacBio sequencing to investigate the effects of treatment with lactic acid bacteria or antibiotics on cow endometritis. Electron J Biotechnol 2021:51. https://doi.org/10.1016/j.ejbt.2021.02.004

Labetalol hydrochloride (LHCl), an α- and β-adrenoreceptor blocker, is widely used for the treatment of hypertension as well as angina pectoris. Previous reports have demonstrated the adverse events during clinical application of LHCl, such as liver injury and acute renal failure. The present study aimed to investigate metabolic activation of LHCl to initiate the elucidation of the mechanisms of its liver toxicity. One glutathione (GSH) conjugate was detected in rat and human primary hepatocytes as well as bile of rats after exposure to LHCl. The GSH conjugate was chemically synthesized and characterized by Q-TOF and 1H NMR. Pretreatment of 2,6-dichloro-4-nitrophenol (DCNP), a broad-spectrum sulfotransferase (SULT) inhibitor, significantly attenuated the formation of the GSH conjugate in LHCl-treated hepatocytes and animals, indicating the participation of SULTs in metabolic activation of LHCl. Moreover, pretreatment with DCNP displayed significant protection against the observed cytotoxicity in rat primary hepatocytes, which suggests a correlation of the bioactivation of LHCl mediated by SULTs with LHCl-induced hepatotoxicity.

Currently, developing high-performance non-noble metal catalysts for the conversion of biomass-derived compounds to valuable chemicals or biofuels remains a great challenge. Herein, surface CoFeOₓ-decorated bimetallic CoFe catalysts were developed via a Co–Mg–Fe layered double hydroxide precursor strategy and utilized for the transfer hydrogenolysis of 5-hydromethylfurfural (HMF) into 2,5-dimethylfuran (DMF) with the help of formic acid as the sustainable hydrogen donor. The as-fabricated CoFe bimetallic catalyst exhibited excellent catalytic performance with a high yield of DMF (>92%). Contrarily, monometallic Co-based catalyst delivered a much lower DMF yield. The structural characterizations and catalytic experiments demonstrated that the catalytic behavior of bimetallic CoFe catalysts was correlated with the appropriate combination of highly dispersed bimetallic metallic nanoparticles and abundant oxygen vacancies originating from surface CoFeOₓ species, as well as favorable surface basic sites, thereby facilitating the dehydrogenation of formic acid and improving the affinity for carbonyl reduction, which promoted the selective hydrogenation/hydrogenolysis of carbonyl or hydroxymethyl group in HMF and reaction intermediates. Furthermore, excellent structural advantages of as-fabricated CoFe catalyst, such as high alloying degree of CoFe and strong metal–support interactions, endowed it with good stability and regeneration performance. The present bimetal-defect interfacial engineering strategy may provide a potential guide for the rational design of high-performance non-noble-metal catalysts for a variety of heterogeneous catalysis processes in terms of the conversion of biomass source.

Environmental pollutants are difficult to degrade and easy to accumulate, which pose a serious threat to human health and ecological environment. Therefore, the rapid and sensitive detection of pollutants is crucially important. Metal nanoclusters (MNCs) have shown good application prospects in the field of chemical sensing due to their small size, high stability, short preparation time and easy modification. As a new type of fluorescent nanomaterials, MNCs have attracted much attention in the field of pollutant detection. In this paper, the research progress of MNCs in detecting heavy metal ions, sulfides, cyanides, polynitroaromatics, formaldehyde, organic pesticides, bacteria and viruses in recent years is summarized, and the development prospect of MNCs is discussed.

Currently, the development of high-performance and stable non-noble metal catalysts for low-temperature CO2 methanation is quite challenging for practical industrial applications in terms of highly efficient and renewable energy storage and conversion. In this work, highly dispersed Ni nanoparticles over a perovskite-type AlCeO3 solid-solution support as catalysts for exceptional low-temperature CO2 methanation were synthesized via an innovative single-source Ni–Al–Ce layered double hydroxide (LDH) precursor route. It was demonstrated that the as-fabricated Ni-based catalyst with a Ce/(Ce + Al) molar ratio of 0.2 displayed superior low-temperature catalytic activity for CO2 methanation compared to the Ce-free Ni catalyst and Ni/CeO2 and Ni/Al2O3 catalysts obtained via the impregnation method for comparison, with a high CO2 conversion of 83.2% at only 200 °C and a high CO2 turnover frequency value of 18.2 h−1 achieved at a low reaction temperature of 175 °C. This remarkable low-temperature activity of the catalyst for CO2 methanation outperforms all other supported Ni catalysts reported thus far. It was verified that the favorable Ce3+ sites in the perovskite-type AlCeO3 solid solution contribute to the enhanced medium-strength surface basicity, which is beneficial for CO2 adsorption and the formation of formate intermediate species, thus greatly accelerating the transformation of formate intermediates to the target methane product. Furthermore, for the Ni/AlCe-0.2 catalyst, no deactivation could be observed, indicating the good stability and reusability of the Ce-containing Ni-based catalysts. The present findings provide a new stable and high-performance non-noble metal-based catalyst by integrating Ni nanoparticles with perovskite-type AlCeO3 solid-solution support for exceptional low-temperature CO2 methanation.

Glaucoma is a leading cause of irreversible blindness worldwide. This study evaluates the reduction of intraocular pressure (IOP) induced by C. cicadae mycelia extract in a steroid-induced rat model of glaucoma. Cordyceps cicadae mycelia is a well-known and valued traditional Chinese herbal medicine. C. cicadae mycelia were cultured using a liquid fermentation technique. The harvested C. cicadae mycelia were then lyophilized and extracted with two solvents, water and ethanol. The aqueous extract (CCM-DW) and ethanolic extract (CCM-EtOH) of the mycelia were obtained through lyophilization. Sprague Dawley rats were randomly divided into four groups (n = 6 in each group): a normal group, a control group, and experimental groups treated with CCM-DW, or CCM-EtOH (both at 50 mg/kg/body weight). Except for those in the normal group, all rats received a subconjunctival injection of betamethasone to induce high IOP. The rats in the experimental groups received a daily administration of CCM by oral gavage for four consecutive weeks. IOP reduction is the known treatment for glaucoma. The results revealed that steroid treatment caused a significant increase in the animals' IOP (control group). Elevated IOP decreased significantly after treatment with CCM-DW and CCM-EtOH (p < 0.01), and CCM-DW was more effective than CCM-EtOH. CCM-DW and CCM-EtOH were capable of causing significant decreases in high IOP-induced lesions in pathological studies in which it was shown that the efficacy of CCM-DW surpassed that of CCM-EtOH. After CCM-DW administration for 28 days, there were significant decreases in malondialdehyde and lactate dehydrogenase levels and significant increases in catalase, superoxide dismutase, and glutathione peroxidase levels. In summary, C. cicadae mycelia may be beneficial for preventing or treating glaucoma due to its significant IOP-lowering and antioxidant activities.

Electrocatalytic nitrogen reduction reaction (NRR) to generate ammonium is a promising renewable technology for nitrogen cycling. Engineering the composition and surface states of an electrocatalyst is critical to improve the intrinsic NRR performance. Here, a facile preparation of Ni nanoparticles (NPs) loaded on V4C3Tx MXene (denoted as Ni@MX) as a highly efficient NRR electrocatalyst is reported. Remarkably, the Ni@MX nanocomposite presents an ammonia yield rate of 21.29 μg h−1 mgcat−1 at 0.2 mA cm−2. The presented NRR activity is considerably higher than that of the recently reported MXene derivatives and is even comparable to that of the noble-metal-based electrocatalysts. Combined with various characterization methods and the density functional theory (DFT) simulation, we propose that the improved NRR activity was ascribed to a synergistic NRR route by Ni sites in the nanoparticles and the surface O vacancy of V4C3Tx MXene. Given the remarkable improvement of NRR activity on the MXene-based nanocomposites, this work demonstrates the critical role of MXene and its derivatives with surface modification as electrocatalysts.

Currently, the catalytic transformation and utilization of biomass-derived compounds are of great importance to the alleviation of environmental problems and sustainable development. Among them, furfural alcohol derived from biomass resources has been found to be one of the most prospective biomass platforms for high-value chemicals and biofuels. Herein, high-surface-area ZrO2 with abundant oxygen defects and surface acid-base sites was synthesized and used as a heterogeneous catalyst for the catalytic transfer hydrogenation of furfural into furfural alcohol using alcohol as a hydrogen donor. The as-synthesized ZrO2 exhibited excellent catalytic performance with 98.2% FA conversion and 97.1% FOL selectivity, even comparable with that of a homogeneous Lewis acid catalyst. A series of characterization studies and experimental results revealed that acid sites on the surface of ZrO2 could adsorb and activate the C[double bond, length as m-dash]O bond in furfural and base sites could facilitate the formation of alkoxide species. The synergistic effect of surface acid-base sites affords a harmonious environment for the reaction, which is crucial for catalytic transfer hydrogenation of furfural with high efficiency. Furthermore, the as-prepared ZrO2 catalyst also exhibited a potential application for the efficient catalytic transfer hydrogenation of a series of biomass-derived carbonyl compounds.

We reported the modification of a NiAl-layered double hydroxide (LDH) by loading well-dispersed CoPd alloys through a NaBH4 reduction method. The modified NiAl-LDH achieved 14.5-fold and 2.1-fold improvements of the H2 and CO evolution rates and an applicable ratio of H2/CO (nearly 1 : 1) under visible light (λ > 420 nm). This study revealed the potential of alloys to adjust the H2/CO ratio and enhance syngas production for LDHs for the first time.

Introduction Interleukin-1 receptor-associated kinase 1 (IRAK1) was shown to contribute to a variety of cancer-related processes. However, the function of IRAK1 in hepatocellular carcinoma (HCC) pathogenesis has not been investigated in detail. Methods IRAK1 expression in HCC was examined by immunohistochemistry, qRT-PCR, and Western blot assays. In addition, Huh7 and Hep3B cells were transfected with IRAK1 siRNAs and/or a NOD-like receptor family pyrindomain containing 3 (NLRP3) plasmid. Western blot, EdU staining, and Transwell assays were performed to determine changes of apoptosis, proliferation, migration, and invasion in HCC cells. Moreover, changes in the expression of proteins involved in the MAPKs/NLRP3/IL-1β pathway were confirmed by Western blotting. Results IRAK1 was found to be highly upregulated in HCC tissues and cells. Knockdown of IRAK1 signaling prevented the proliferation, invasion, migration, epithelial–mesenchymal transition (EMT) of HCC cells. Mechanistically, we found that activation of the MAPKs/NLRP3/IL-1β pathway could be markedly suppressed by IRAK1 knockdown in HCC cells. Furthermore, our data showed that NLRP3 could partially reverse the reduced aggressive biological behaviors of HCC cells which were caused by RAK1 knockdown. Conclusion Knockdown of IRAK1 prevented HCC progression by inhibiting the ability of NLRP3 to block the MAPKs/IL-1β pathway, suggesting that approach as a strategy for treating HCC.

Diffuse plane xanthomas (DPX) is a rare, chronic, metabolic skin disease which can seriously affect the appearance of the patients and result in psychological problems. Existing treatments are seriously limited. Our objective was to assess the efficacy of and tolerance to simvastatin ointment for the treatment of skin lesions in seven DPX patients. In this study, patients were treated twice daily on the right side of the lesions for 10 months with the 1% or 5% simvastatin ointment. Meanwhile, the left body was untreated as a contralateral controlled side. Efficacy was assessed via the change of rash and was further confirmed by histological study. For all seven participants, both the 1% and 5% simvastatin ointments were effective. The histological change in DPX showed significant decrease of foam cells in skin lesions. The immunohistochemical staining of CD68, macrophage scavenger receptor type 1, oxidized low-density lipoprotein receptor 1 and Oil Red O became obviously reduced after treatment. The test medicines were safe with only some skin-related side-effects. This is the first research reported on simvastatin ointment treatment in DPX. Our results are the first to suggest that simvastatin ointment is effective in improving skin lesions of DPX clinically and histopathologically.

The solubilities in the system NaCl–Na2SO4–NaB(OH)4–H2O and its subsystems were calculated with two models based on Pitzer model. The model I assumes that there are four boron species corresponding to B(OH)3, B(OH)4–, B3O3(OH)4– and B4O5(OH)42– along with OH– in the solution. The model II assumes only one boron species B(OH)4– in the solution. The calculated solubilities are in accordance with the experimental data in the ternary systems NaCl–NaB(OH)4–H2O and Na2SO4–NaB(OH)4–H2O. The assumption of only one boron species B(OH)4− can be applied in the solubility calculation for the systems containing metaborate. The distribution of four boron species were obtained with model I in the borate solution. The mole fraction of the four boron species are mainly affected with the total boron concentration in the solution, but rarely effected by the concentration of Cl– and SO42–. B(OH)4− is the dominant boron species in the metaborate solution. The phase diagram and Pitzer model for the quaternary system were then used to conduct evaporation simulation. The evaporation-crystallization route and order of salt precipitation during the evaporation were demonstrated. The results of the evaporation simulation of brine can be used as a theoretical reference for salt separation and purification from brine resources.

Multifunctional textiles based on cotton have attracted wide attentions recently. In this study, the cotton fabrics were synergistically modified by surface micro-dissolution and cationization to enrich the adsorption of negatively charged graphene oxide (GO) on it. Subsequently, the bound GO was chemically reduced to rGO by using L-Ascorbic acid to endow cotton with high UV resistance and conductivity. By XRD, FTIR and zeta potential analysis, it was concluded that the synergistic modification could alter the structure of cotton and at the same time facilitate the reactions between cotton molecules and cationic agent EPTAC. This would shield more negative charges in cotton to decrease its absolute zeta potential, enhancing the uptake of negatively charged GO on the surface of cotton significantly. In addition, SEM, FTIR and Raman spectroscopy were utilized to confirm the presence of rGO on the surface of cotton fabrics. The result from resistance measurement disclosed that the synergistic modification could significantly reduce the electrical surface resistance of cotton to 3.89 × 103 Ω/sq. Moreover, the synergistic modification could greatly improve the UV protection factor (UPF) of cotton from 24.18 to 487.91, far beyond the excellent UPF rating (50+). The high UV resistance and conductivity of this rGO coated cotton fabrics suggests that they can be used as functional textiles for various applications.

For heterogeneous supported catalysts, commonly, the adsorption of reactant molecules on the catalyst surface can significantly govern their activity and selectivity. In this paper, it was shown th...

This paper demonstrates a model kit comprising a series of silicone balls with magnets embedded in different predesigned configurations, which can be used to construct stable models of close-packed...

The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.

Rationale: Macrophages play critical roles in the pathogenesis of type 1 diabetes mellitus (T1DM). Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures, implicated in various disease processes. However, their impact on macrophage activation and T1DM pathogenesis remains elusive. Methods: circRNA expression profiles of peripheral blood mononuclear cells (PBMCs) from T1DM children were determined by whole transcriptome microarray. Bioinformatics, quantitative real-time PCR, Western blot, RNA immunoprecipitation (RIP), cell co-culture, cell proliferation, and cell apoptosis assays were performed to investigate the expression, function, and regulatory mechanisms of circPPM1F in vitro. The regulatory role of circPPM1F in vivo was evaluated in the streptozocin-induced diabetic mouse model. Results: We identified 27 upregulated and 31 downregulated differentially expressed circRNAs in T1DM patients. circPPM1F, a circRNA with unknown function, was dominantly expressed in monocytes and significantly upregulated in T1DM patients. Functionally, circPPM1F promoted lipopolysaccharide (LPS)-induced M1 macrophage activation via enhancement of the NF-κB signaling pathway. Mechanistically, circPPM1F competitively interacted with HuR to impair the translation of protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F), thus alleviating the inhibitory effect of PPM1F on the NF-κB pathway. Moreover, eukaryotic initiation factor 4A-III (EIF4A3) and fused in sarcoma (FUS) coordinately regulated circPPM1F expression during M1 macrophage activation. In addition, circPPM1F could exacerbate pancreas injury in the streptozocin-induced diabetic mice by activation of M1 macrophages in vivo. Conclusions: circPPM1F is a novel positive regulator of M1 macrophage activation through the circPPM1F-HuR-PPM1F-NF-κB axis. Overexpression of circPPM1F could promote pancreatic islet injury by enhancing M1 macrophage activation and circPPM1F may serve as a novel potential therapeutic target for T1DM in children.

A new oligothiophene derivative (3TY) was synthesized, and used as a highly selective hydrazine (N2H4) chemosensor in ∼100% aqueous solution with “naked-eye” colorimetric and “turn-on” fluorimetric response. This chemosensor 3TY enabled ultrafast and ultrasensitive detection of hydrazine with ultralow detection limit of 1.45 nM (0.04 ppb) in a wide sensing pH range from 6 to 10. The sensing mechanism of 3TY toward hydrazine was strongly and fully confirmed. More importantly, colorimetric paper test strip and solid support silica are easily prepared by 3TY for on-site and real-time detection of hydrazine. Furthermore, 3TY displays many potential applications for detecting N2H4 in environmental water and human urine along with bio-imaging in living HeLa cells.