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This research aimed to study the inhibitory effect of Glurenorm (gliquidone) on epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells based on the diabetic nephropathy (DN) model. In this study, 30 specific pathogen-free (SPF) mice were selected to construct DN model and randomly rolled into groups A, B, and C, with 10 mice in each group. Low-dose, mediumdose, and high-dose Glurenorm were administered intragastrically. The results showed that the serum urea nitrogen content (7.23±0.39 mmol/L, 6.18±0.46 mmol/L) of control and C group was considerably inferior to A group (8.01±0.48 mmol/L), and the content of C group was greatly lower than controls (P < 0.05). The creatinine clearance rate (2.97±0.44 mL/min, 4.02±0.31 mL/min) of mice in control and C group was notably superior to A group (2.18±0.38 mL/min), and that of C group was obviously higher versus controls (P < 0.05). After 5 weeks of intragastric intervention by Glurenorm, the body mass of the mice in control and C group was evidently lower relative to A group, and that of C group was obviously higher versus controls (P < 0.05). Mice in control and C group were remarkably lower in body mass at the 7th week after Glurenorm intervention versus A group, and C group was relatively lower versus controls (P < 0.05). In short, EMT played an important role in promoting the occurrence and progression of renal fibrosis. Glurenorm can reduce the progression of renal fibrosis, inhibit EMT of renal tubular epithelial cells, and effectively protect kidney function.

Herein, nanocomposites films were prepared via the facile casting method by incorporating cellulose nanocrystals (CNCs) with arabinogalactan (AG), galactomannan (GM) or konjac glucomannan (KGM) respectively. The introduced polysaccharides maintained the transparency of CNCs films and promoted the UV blocking properties. In addition, mechanical strength of the nanocomposite films was greatly improved after the combination of polysaccharides. The interactions of hydroxyl-abundant macromolecules, smoother and tighter morphological structures, as well as the disturbed crystal structure were proved to be responsible for the improved properties. Hydrophilic lattice planes of cellulose crystallites were determined to interact with polysaccharides resulting in lower crystallite sizes and crystallinity. The cell culture assay revealed that the films had no cytotoxicity and presented a satisfactory cytocompatibility, because of the polysaccharides from plant cell walls introduced into the films. Therefore, the biocompatible nanocomposites films can be tuned by the addition of polysaccharides, which show great potentials for materials modification in optical, packaging and biomedical fields.

To explore the effect of different positions and number of pyrrolidine bound to the carbon cage on the stabilization effect of fulleropyrrolidine derivatives to nitrocellulose (NC)/nitroglycerine (NG), we synthesized N-(4-methoxy) phenylpyrrolidine-C60 and four different of bis(N-(4-methoxy) phenylpyrrolidine)-C60 compounds through Prato reaction. Their structures were characterized by UV–vis, 1H NMR, 13C NMR, high-resolution mass spectroscopy, and single-crystal X-ray diffraction. Their stabilization effect to NC/NG were investigated using differential scanning calorimetry, methyl violet, vacuum stabilization effect, weight loss, and accelerating rate calorimeter tests. The results indicated these compounds had excellent stabilization effect to NC/NG. The stabilization effect of the fulleropyrrolidine bisadducts to NC/NG is significantly better than that of fulleropyrrolidine monoadduct and C60. Moreover, the position where pyrrolidine binds to fullerene in fulleropyrrolidine bisadducts is different, and its stabilization effect to NC is also different. The stabilization effect order of different bisadduct isomers to nitrocellulose is as follows: e-edge > trans-2> cis-2> trans-3. Electron paramagnetic resonance (EPR) and FT-IR were used to study the stabilization mechanism of fulleropyrrolidine derivatives to NC/NG. The EPR results also show that fulleropyrrolidine bisadducts with different addition sites have different abilities to absorb nitroxide, and their ability is better than that of the monoadduct and C60, which is consistent with the results of stabilization effect performance test.

Pt-based heterogeneous metal catalysts are commonly used in the hydrogenation of nitro groups. However, the continuous large metal domain size and the complex interaction between the substrates and metal surface usually inevitably result in side reactions, such as dehalogenation of halogenated nitroaromatics. In this work, by simply treating the Pt-based catalysts with CO at elevated temperature, the Boudouard reaction taking place on Pt surface results in the deposition of carbon species thereon. The carbon deposition not only inhibits the dehalogenation by restricting the planar interaction of the aromatic group with the Pt surface that is segmented by C, the hydrogenation activity of the nitro group is also enhanced on the partially positively charged surface Pt sites created by the electron-withdrawing interstitial C. Such a simple treatment strategy is effective for fabricating Pt-based catalysts on different supports toward the selective hydrogenation of a wide range of halogenated nitroaromatics.

A large amount of iodine-containing solution (ICS) is produced in both nuclear medicine and the atomic energy industry, which may cause serious health hazards in case if it enters aquatic ecosystem without sufficient treatment. The treatment of ICS by silver demonstrates great potential for iodine capture and retention. Nano-scale silver and its oxide particles formed on the surface of Al2O3 via electroless plating was introduced to ICS treatment. A series of batch sorption experiments against ICS by Ag-Ag2O modified Al2O3 (Ag-Ag2O-Al2O3) has been conducted. Ag-Ag2O-Al2O3 was characterized by SEM, FTIR, XRD, and XPS before and after the reaction. The results show that ~ 82.6% of I− was removed by 4.0 g/L Ag-Ag2O-Al2O3 from the solution containing 0.3 mg/L I− at pH 3 and at 298 K. Ag-Ag2O-Al2O3 was effective in low concentration artificial nuclear medical ICS treatment. Thermodynamic analysis showed that the reaction consistent with the Langmuir model and was a uniform exothermic reaction of a single layer. Therefore, Ag-Ag2O-Al2O3 prepared by electroless plating could be considered as a potential material for the ICS treatment.

The influence of surface modification of SiO2 carrier by grafting method and its effects for Rh supporting was investigated on formaldehyde hydroformylation reaction. The relationship between the structure of catalysts and their performance was characterized in detail by X-ray diffraction, N2 adsorption–desorption, temperature programmed reduction with H2, X-ray photoelectron spectroscopy, and in situ infrared. After grafting the amino organic functional group, the surface circumstance of SiO2 was altered, and moreover, sites available for metal loading was enriched on the carrier that distribute a high dispersion of Rh species Under the same Rh loading, the Rh@N–SiO2 catalyst exhibits better catalytic activity than pristine SiO2 supported Rh catalysts. Spectroscopic evidences suggest the presence of an electronic perturbation between Rh and modified SiO2 which promotes the hydroformylation of formaldehyde by maintaining Rh at proper Rh0/(Rh3+ + Rhδ+) ratio. Diagram of the effect of surface modified with amino group on metal rhodium loading.

Chen-Jie Liu,1 Li Yao,2 Ya-Min Hu,2 Bo-Tao Zhao2 1ECG Room of Physical Examination Center of Cangzhou Central Hospital, Cangzhou, Hebei, 061001, People’s Republic of China; 2Six Cardiovascular Departments of Cangzhou Central Hospital, Cangzhou, Hebei, 061001, People’s Republic of ChinaCorrespondence: Chen-Jie LiuECG Room of Physical Examination Center of Cangzhou Central Hospital, No. 5 Guangrong Road, Canal District, Cangzhou, Hebei Province, 061001, People’s Republic of ChinaEmail liuchenjiecz@163.comBackground: Quercetin has potential value in treating cardiovascular diseases, but it is not suitable for clinical application due to its own water solubility. The limitation of quercetin can be distinctly ameliorated by delivering it with nanocarriers.Objective: To determine the effect of quercetin-loaded mesoporous silica nanoparticles (Q-MSNs) on myocardial ischemia-reperfusion injury in rats and its mechanism.Methods: Q-MSNs were synthesized, and the morphology of Q-MSNs and MSNs was characterized by transmission electron microscopy and dynamic light scattering technique, respectively. Healthy rats were enrolled and randomly divided into a sham operation control group, an ischemia-reperfusion (IR) group, an IR+Q group, an IR+Q-MSNs group, and an MSNs group (each n = 10). Rats in the sham operation group were not treated with ischemia reperfusion, but given normal perfusion meantime. Rats in the sham operation control group, IR group, and MSNs group were given normal saline for 10 days before ischemia reperfusion, and rats in the IR+Q group and IR+Q-MSNs group were given drugs by gavage for 10 days before ischemia reperfusion. Primary myocardial cells were sampled from SD neonatal rats to construct hypoxia/reoxygenation myocardial cell models. The myocardial cells were assigned to a control group, IR group, quercetin (Q) group, Q-MSNs group, and MSNs group. Except for the control group, all the other groups were treated with hypoxia/reoxygenation. Cells in the Q group were treated with quercetin (10 μM, 20 μM, 40 μM) for 24 h in advance and then treated with measures to cause hypoxia-reoxygenation injury. Cells in the Q-MSNs group were treated with the same concentration of loaded quercetin and the same method used for the Q group. The myocardial apoptosis, myocardial infarction, ventricular remodeling, hemodynamic indexes, physiological and biochemical indexes, and JAK2/STAT3 pathway expression of each group were detected, and the apoptosis, viability, oxidative stress, and JAK2/STAT3 pathway expression of primary myocardial cells in each group were also detected.Results: Quercetin significantly activated the JAK2/STAT3 pathway in vivo and in vitro, and MSNs intensified the activation. Compared with quercetin, Q-MSNs were more effective in inhibiting cell apoptosis and oxidative stress, reducing myocardial infarction size, improving ventricular remodeling and cardiac function-related biochemical indexes, and promoting the recovery of cardiac blood flow.Conclusion: Q-MSNs can significantly enhance the activation effect of quercetin on JAK2/STAT3 pathway, thus enhancing its protection on the heart of MIRI rats.Keywords: myocardial ischemia-reperfusion injury, quercetin-loaded mesoporous silica nanoparticles, JAK2/STAT3 pathway, cardiovascular diseases

Graphical abstract, Introduction Eugenol is a major component of essential oils of several plants, it exhibits significant antiparasitic and acaricidal activities, yet its molecular targets remain unknown. Objectives We aimed to systematically investigate the mechanism of action and the potential targets of eugenol against P. cuniculi, and evaluate the safety for laying the theoretical foundation for clinical application as an acaricide. Methods Using RNA-Seq analysis, surface plasmon resonance analysis and RNA interference assay, the mode of action of eugenol against Psoroptes cuniculi was investigated. The effect on the mitochondrial membrane potential and complex I of PC12 cells and C6/36 cells was assayed to investigate the species specificity of eugenol in insects and mammals. Finally, a safety evaluation of eugenol in vivo was performed. Results Eugenol inhibited complex I activity of the mitochondrial respiratory chain in the oxidative phosphorylation pathway by binding to NADH dehydrogenase chain 2 and resulted in the death of mites. The inhibition rates were 37.89% for 50 μg/mL and 60.26% for 100 μg/mL, respectively. Further experiments indicated that the difference in the complex I sequence between insects and mammals led to the different affinity of eugenol to specific peptide, resulting in species specificity. Eugenol exhibited significant inhibitory effects against the mitochondrial membrane potential and complex I in Aedes albopictus C6/36 cells but was not active in rat PC12 cells. Insect cells were particularly sensitive to eugenol. In contrast to the known inhibitor rotenone, eugenol had better safety and did not result in Parkinson’s disease or other diseases in rats. Conclusion This is the first report on acaricidal eugenol targeting complex I of the mitochondrial respiratory chain. This work lays the foundation for the development of eugenol as an environmentally alternative acaricidal agent.

Indolizidine alkaloids are chemical constituents isolated from various marine and terrestrial plants and animals, including but not limited to trees, fungi, ants, and frogs, with a myriad of important biological activities. In this review, we discuss the biological activity and pharmacological effects of indolizidine alkaloids and offer new avenues toward the discovery of new and better drugs based on these naturally occurring compounds.

Several quorum sensing systems occurring in Bacillus subtilis, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in Bacillus velezensis NAU-B3. We found that the rapA4 and phrA4 genes were co-transcribed in NAU-B3. When rapA4 was expressed in the heterologous host Bacillus subtilis OKB105, surfactin production and sporulation were severely inhibited. However, when the phrA4 was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase srfA gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the srfA operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment. KEY POINTS: •Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42. •RapA4-PhrA4 regulates surfactin production and sporulation. •RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.

Cancer is a common disease that poses a serious threat to human health. Angiogenesis is essential for the growth and metabolism of tumors, providing oxygen and nutrition for the growth of cells and tissues. However, angiogenesis of tumors depends on the stimulation of growth factors. Vascular Endothelial Growth Factor (VEGFR) is the most unique factor. Therefore, VEGF/VEGFR targeting anticancer drugs are playing an increasingly significant role in clinical trials. In addition, it has been proved that chalcone, the precursor of natural flavonoids, has potential anti-tumor activity, especially anti-angiogenesis activity. This review summarizes the reports about the anti-angiogenesis of chalcone derivatives. Based on the chalcone skeleton, it is divided into substituted chalcones and modified chalcones. The anti-angiogenesis activities of natural or synthetic chalcones, benzene ring modified or connecting bridge modified chalcones are described in this review.

Purpose This study aims to investigate the effect of combined use of granular graphite and petroleum coke on the properties of copper-based friction materials and the friction and wear mechanisms. Design/methodology/approach Copper-based friction materials with different proportions of petroleum coke and granular graphite were prepared by using powder metallurgy. The friction surfaces were analyzed. Findings Changing the ratio of petroleum coke/granular graphite affects the formation of oxides and sulfides on the surface of the materials. Increasing the petroleum coke promotes the production of metal sulfide and sulfate in the friction materials and reduces coefficient of friction (COF) and wear. Increasing petroleum coke also increases the amount of carbonic oxide (CO) released during the braking process and promotes the reduction process of iron oxide on the friction surface. Originality/value The synergistic effect of carbon materials on copper-based friction materials was studied in terms of the tribological chemical reaction. This research provides useful information for the selection of carbon materials in friction materials. Peer review The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-02-2020-0075/

This paper explored a solid-phase reduction method to prepare ultrafine nickel powder under different conditions. The effect of a NaCl separator agent on the morphology, primary particle size and specific surface area of the prepared nickel powder is discussed. The results show that direct contact among primary Ni particles can be effectively inhibited during the reduction of nickel oxalate due to the presence of the NaCl separator agent. An ultrafine nickel powder with a primary particle size of between 80 and 150 nm can be prepared with NaCl as the separator agent at temperatures from 400 °C to 460 °C. The powder reduced at 430 °C has a uniform particle distribution and a decreased amount of agglomeration.

Advanced Glycation End Products (AGEs) could be formed with α-dicarbonyl compounds as intermediates; however, simultaneous determination of AGES as well as their precursors and intermediates have rarely been mentioned, so as to investigate the reaction. In this work, lysine was reacted with aldoses (galactose, glucose) and ketoses (fructose, sorbose) to investigate the effects of sugar type and heating temperature. Two high-performance liquid chromatography-tandem mass spectrometry methods were developed to quantify AGEs and the corresponding α-dicarbonyl compounds. The results demonstrated that aldoses were more prone to form intermediates and final products than ketoses from the point of view of absorbance (at 294 and 420 nm). Aldose systems were prone to form glyoxal, whereas ketose systems tended to generate methylglyoxal and 3-deoxyglucosone. The relative reaction activity of sugars in forming Nε-carboxymethyl-lysine depended upon heating temperature for aldose and ketose systems. The aldose was more liable to generate Nε-Carboxyethyl-lysine (CEL) than ketose, with the CEL generation for each sugar occurred in the order galactose > glucose > sorbose > fructose. The obvious differences between different types of sugars suggest that further research is needed on the degradation of sugars to form intermediates and on the reaction of α-dicarbonyl to generate AGEs.

Erosion control materials with long-term effective, economical and environmentally friendly properties play a critical role in controlling erodible and unstable sandy slopes deformed under rainfall. In this study, a novel cellulose-based curing agent was developed and applied as a sustainable sand fixation materisal. The novel cellulose-based curing agent was a dual-polymer composite material (DPCM), which was prepared by mixing two kinds of organic polymer materials: carboxymethyl cellulose (CMC) and polyacrylamide (PAM). The microstructure and composition of DPCM were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The adsorption kinetics of the curing agent on sand particles was discussed by fitting with pseudo-first-order and pseudo-second-order kinetic models. Water resistance and the compressive strength of the sand-fixing specimen at different curing ages were studied. Finally, the DPCM stabilization layer’s resistance to water erosion was investigated using a rainfall simulation test. The results demonstrated that the adsorption kinetic behavior of DPCM adsorbed on sand particles followed pseudo-second-order kinetics. Additionally, the interaction between the DPCM and sand particles was primarily hydrogen bonding, covalent bonds, and physical adsorption. The compressive stress was in the range from 53 to 915 kPa. Sandy slopes treated by DPCM showed excellent resistance to water erosion under a rainfall intensity of 120 mm/h.

The amino poly-siloxane was modified with self-made polyether silicones by the crafts of emulsion polymerization. We studied the emulsifier, the dosage of emulsifier initiator, polyether/silane coupling agent, pH value. There are some results of the research indicated in the following. First, there are many factors for the hydrophilic amino-silicone softener both on the polymerization process and the performance, such as the proportion and amount of emulsifier, initiator dosage, the mass ratio of the polyether and hydrogen silicone oil, the choice of silicone coupling agent, and the ratio and dosage of polyether silicones silane coupling agent. Second, the amount of hydrogen of the hydrogen silicones and the choice of catalyst are the key points on the synthesis of polyether silicones. The amount of hydrogen should be low and the catalyst must be economical and efficient and its introduction should be small and times, other more the holding time is not too long. The next one is that, in the process of hydrolysis of silane coupling agent, we need some acid to adjust pH value, or they will be broken down. The most important one but not the last is that the epoxy group can improve the products low-temperature supple and the persistence of the finishing fabric, furthermore it can reduce yellowing and has a good stability of the inorganic salt, however, it will be destroyed if the reaction temperature for epoxy is too high. What’s more, it is very economical and environmental that the process of emulsion is simple and with less emulsifier.

Multidrug resistance (MDR) remains a huge obstacle during cancer treatment. One of the most studied MDR mechanisms is P-glycoprotein (P-gp) mediated drug efflux. Based on the three-dimensional structural characteristics of P-gp, gold nanoparticles (AuNPs) with average sizes of 4.1 nm and 5.4 nm were designed for the construction of nanodrug delivery systems (NanoDDSs), with the anticancer molecules 2-(9-anthracenylmethylene)-hydrazinecarbothioamide (ANS) and 6-mercaptopurine (6-MP) modified on the AuNP surfaces through the thiol group. In vitro cytotoxicity results suggested that the larger sized AuNPs can effectively decrease the drug resistance index of MCF-7/ADR cells to ∼2. Verapamil and P-gp antibody competitive experiments, combined with the cellular uptake of AuNPs, indicated that larger NanoDDSs were more conducive to intracellular drug accumulation and thus had improved anticancer activities, due to a size mismatch between the nanoparticles and the active site of P-gp, and, therefore, reduced drug efflux was seen. Measurements of ATPase activity and intracellular ATP levels indicated that the larger nanoparticles do not bind well to P-gp, thus avoiding effective recognition by P-gp. This was further evidenced by the observation that 4.1 nm and 5.4 nm NanoDDS-treated MCF-7/ADR cells showed remarkable differences in energy-related metabolic pathways. Therefore, the critical size of AuNPs for overcoming MDR was identified to be between 4.1 nm and 5.4 nm. This provides a more accurate description of the composite dimension requirements for NanoDDSs that are designed to overcome MDR.

Background Lung cancer is the most revenant and deadly tumors around the world. Here we aimed to explore the effects of hepatocyte nuclear factor 1B (HNF1B) and PCDHA13 overexpression on PI3K/AKT phosphorylation and malignant biological behavior in lung cancer A549 cells. Methods HNF1B and PCDHA13 were amplified, and their overexpression plasmids were constructed for transfection. RT-PCR was used to detect the mRNA levels of HNF1B and PCDHA13. Cell proliferation and cell apoptosis were detected by clone formation experiments and flow cytometry, respectively, while cell invasion was studied by Transwell assay. The expression of survivin, PCNA, Caspase-3, Caspase-9, VEGF, and fibronectin was detected using immunoblotting, as was PI3K/AKT phosphorylation. Results The level of HNF1B mRNA expression was significantly higher in the pcNDA-HNF1B group than in the control group (P

Electrochemical impedance spectroscopy (EIS) has been used in various applications, such as metal corrosion monitoring. However, many conventional corrosion monitoring setups are bulky and inconvenient for in-situ testing. The purpose of this work is to reduce the size of the whole corrosion monitoring system. We utilized EIS to design a field deployable impedance-based corrosion sensor (FDICS), capable of performing in-situ EIS analysis. Experiments verified the sensor’s accuracy, and the results showed that the sensor performed similarly to a bench-top EIS machine when we tested on circuit models. Furthermore, we used the proposed FDICS to monitor a metal corrosion experiment and performed EIS. The result showed that the proposed FDICS is able to obtain the sample’s impedance spectroscopy, which could help researchers test its corrosion severity on a metallic sample in-situ. Compared to other bulky conventional setups, our device eliminates the design complexity while still showing insights into the corrosion reaction.

The North Pamir, part of the western syntax of the India-Asia collision zone, preserves remnants of a poorly investigated Paleozoic intra-oceanic subduction zone. To constrain the age of this ancient ocean floor, we analyzed calcite phases in vesicular basalt and basaltic volcanic breccia with U-Pb geochronology using laser-ablation inductively-coupled-plasma mass-spectrometry (LA-ICP-MS). Calcite dating yielded Mississippian ages, mostly overlapping each other within errors. REE + Y data reveal that the basaltic host rock of the calcite and oxidizing seawater are major sources of trace elements during calcite precipitation. U-Pb ages seem to be independent of REE + Y concentrations. Our results demonstrate the potential of calcite dating to constrain the age of ancient ocean floors and provide a test of the hypothesis that a continuous early Paleozoic Kunlun Terrane extended from northern Tibet into the North Pamir.

The insights into the transport mechanism of Pu in granite fractures are indispensable for a reliable safety-assessment of radioactive waste disposal sites. In this work, the study of transport behavior of Pu in a rough single fracture has been performed under different pH conditions. The results indicated that under strong acidic condition the sorption of Pu dominated by ion-exchange reaction is quite weak, reversible and not be affected by the change of flow rates, while under neutral condition the majority of Pu can be adsorbed onto granite surface, controlled by surface-complex reaction between Pu(OH)4(aq) and fracture surface hydroxyl groups.

Multidrug resistance (MDR) and adverse effects of chemotherapeutic agents are severe issues in clinical cancer treatment. Due to the dysregulation of enzymes in the cancer cells, enzyme-responsive drug delivery systems (DDSs) have been considered as a viable technology for cancer chemotherapy. In the present work, doxorubicin (DOX) is visible after leaving from AuNR-LAX. After treatment with AuNR-LAX, the drug resistance index of DOX-resistant MCF-7/ADR cells was reduced from extremely high 955.0 to 1.7, implying high potential of AuNR-LAX in the MDR phenotype cancer treatment. In addition, the cellular viability of both MCF-7 and MCF-7/ADR cells decreased from 50% to 80% after treatment with AuNR-LAX along (equivalent DOX concentration = 2.3 μg/mL, Au concentration = 30 μg/mL) to below 10% after AuNR-LAX treatment plus radiation of 808 nm, due to the NIR photothermal effect of AuNRs. Human bronchial epithelial cell line 16HBE was chosen to evaluate the adverse effect of AuNR-LAX on the normal cells. At the low concentration, the cytotoxicity of LAX and AuNR-LAX is comparable for breast cancer cell MCF-7 and normal cell 16HBE. It is noted that, at high concentration (with equivalent DOX concentration = 13.1 μg/mL, Au concentration = 167.7 μg/mL), the cellular viability of 16HBE cells is over 50%, whereas that of MCF-7 cancer cells is close to 0, implying the potential of AuNR-LAX in reducing the adverse effects of DOX against normal cells/tissues. Overall, AuNR-LAX showed high potential in overcoming MDR and alleviating adverse effect on normal cells.

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of ather...

Nano-sized TiN-reinforced Ti metal matrix composites were fabricated by powder metallurgical route, which includes high-energy ball milling pretreatment and subsequent hot-press sintering treatment. The phase composition and microstructure of the sintered samples were characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Results showed that N2 was absorbed and solubilized into TiH2 by milling pretreatment, and TiN was formed during sintering process and was fine to a grain size of 20–100 nm. The final phase composition of the composites was αTi, βTi, and TiN with solution N in matrix. Mechanical tests showed that with increasing milling time, the hardness of the composites increased by 31, 58, 93, and 101% compared with pure Ti. The compressive strength initially increased and later decreased to 2440 and 2120 MPa when milled for 1.5 and 2 h, respectively.

Rhodamine spirolactams with adjacent amino groups work as acid-resistant and photoswitchable fluorophores in single-molecule localization super-resolution imaging., Rhodamine spirolactam based photoswitches have been extensively applied in super-resolution single-molecule localization microscopy (SMLM). However, the ring-opening reactions of spirolactams are cross-sensitive to acid, limiting their photoswitch use to neutral pH conditions. In addition, the ring-closing reactions of spirolactams are environment-sensitive and slow (up to hours), virtually making rhodamine spirolactams caged fluorescent dyes instead of reversible photoswitches in SMLM. Herein, by introducing hydrogen bonds to stabilize spirolactams, we report a series of acid-resistant rhodamine spirolactams with accelerated ring-closing reactions from fluorescent xanthyliums to non-fluorescent spirolactams, endowing them with good photoswitchable properties even in acidic environments. By further substitution of 6-phenylethynyl naphthalimide on the spirolactam, we shifted the photoactivation wavelength into the visible region (>400 nm). Subsequently, we have successfully applied these dyes in labeling and imaging the cell surface of Bacillus subtilis at pH 4.5 using SMLM.

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been des...

Ureolytic microbial-induced calcium carbonate precipitation (MICP) is a promising green technique for addressing sustainable building concerns by promoting self-healing mortar development. This paper deals with bacteria-based self-healing mortar under artificial seawater incubation for the sake of fast crack sealing with sufficient calcium resource supply. The ureolytic MICP mechanism was explored by morphology characterization and compositional analysis. With polyvinyl alcohol fiber reinforcement, self-healing mortar beams were produced and bent to generate 0.4 mm width cracks at the bottom. The crack-sealing capacity was evaluated at an age of 7 days, 14 days, and 28 days, suggesting a 1-week and 2-week healing time for 7-day- and 14-day-old samples. However, the 28-day-old ones failed to heal the cracks completely. The precipitation crystals filling the crack gap were identified as mainly vaterite with cell imprints. Moreover, fiber surface was found to be adhered by bacterial precipitates indicating fiber–matrix interfacial bond repair.

Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.

Meat and fermented foods are the main source of vitamin B12 (cobalamin) for human beings. Therefore, daily cobalamin intake is a big problem for vegans. In this study, cyanocobalamin (CNCBL) was added to the culture broth for cobalamin enrichment in spinach. After 36 h of cultivation, the accumulated CNCBL in the spinach leaves (wet weight) was as high as 0.48% (concentration), and the leaves still contained 0.94 ± 0.11 μg/g CNCBL after boiling, which could provide consumer daily requirement of CNCBL. Because CNCBL supplementation had adverse effects on gut microbiota, this study focused on the effect of the combination of spinach and CNCBL on gut microbiota as well. After the boiled leaves were passed through an in vitro gastrointestinal tract simulation system, it was found that the spinach protected CNCBL against the low-pH gastric acid. Moreover, compared with the CNCBL supplement group, the relative abundances of Bacteroides and Firmicutes increased, and the relative abundance of Proteobacteria, especially Escherichia spp., reduced. Analysis of short-chain fatty acids (SCFAs) showed that cobalamin-rich spinach was positively correlated with Bacteroides, propionate, and butyrate. The results showed that the method of enriching spinach with CNCBL was effective and had beneficial effects on gut microbiota and SCFAs.

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio, UACR &gt, 20&ndash, 200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM, Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: &minus, 4.28 &plusmn, 14.92 vs. 9.18 &plusmn, 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 &plusmn, 5.76 vs. &minus, 3.29 &plusmn, 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months, Tocovid improved eGFR (MD: 4.83 &plusmn, 6.78 vs. &minus, 1.45 &plusmn, 9.18), p = 0.022 and serum creatinine (MD: &minus, 7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-&beta, 1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

A polycrystalline sample of Pb2NiOsO6 was synthesized under high-pressure (6 GPa) and high-temperature (1575 K) conditions. Pb2NiOsO6 crystallizes in a monoclinic double perovskite structure with a centrosymmetric space group P2(1)/n at room temperature. Pb2NiOsO6 is metallic down to 2 K and shows a single antiferromagnetic (AFM) transition at T-N = 58 K. Pb2NiOsO6 is a new example of a metallic and AFM oxide with three-dimensional connectivity. Neutron powder diffraction and first-principles calculation studies indicate that both Ni and Os moments are ordered below T-N and the AFM magnetic order breaks inversion symmetry. This loss of inversion symmetry driven by AFM order is unusual in metallic systems, and the 3d-Sd double-perovskite oxides represent a new class of noncentrosymmetric AFM metallic oxides.

Viola yedoensis Makino was used to treat inflammation, viral hepatitis, acute pyogenic infection, and ulcerative carbuncles. However, the protective effect on immunological liver injury (ILI) of V. yedoensis had been rarely reported. This study aimed to explore the protective effect of n-butanol extract (BE) from V. yedoensis on ILI in vitro and in vivo. In vitro, the BE significantly inhibited the secretions of Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) in the HepG2.2.15 cells and the replication of HBV DNA. The research data in vivo revealed that the BE reduced the levels of alanine transaminase (ALT), aspartate transaminase (AST), and methane dicarboxylic aldehyde (MDA) in liver tissues of the ConA-induced mice, while increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and the effective contents of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and the BE could ameliorate liver histological lesions. These results motivated a further investigation into the chemical constituents of BE. Four coumarins (esculetin, prionanthoside, cichoriin, and esculin) and one flavonoid (quercetin-3-O-galactoside) were isolated from the BE by silica gel column chromatography and recrystallization, of which structures were eventually confirmed by 1 H-NMR, 13 C-NMR, and MS.

The development of efficient catalysts for Fischer–Tropsch (FT) synthesis, a core reaction in the utilization of non-petroleum carbon resources to supply energy and chemicals, has attracted much recent attention. ε-Iron carbide (ε-Fe2C) was proposed as the most active iron phase for FT synthesis, but this phase is generally unstable under realistic FT reaction conditions (> 523 K). Here, we succeed in stabilizing pure-phase ε-Fe2C nanocrystals by confining them into graphene layers and obtain an iron-time yield of 1258 μmolCO gFe−1s−1 under realistic FT synthesis conditions, one order of magnitude higher than that of the conventional carbon-supported Fe catalyst. The ε-Fe2C@graphene catalyst is stable at least for 400 h under high-temperature conditions. Density functional theory (DFT) calculations reveal the feasible formation of ε-Fe2C by carburization of α-Fe precursor through interfacial interactions of ε-Fe2C@graphene. This work provides a promising strategy to design highly active and stable Fe-based FT catalysts., ε-Fe2C has been identified as the highly active phase for Fischer-Tropsch synthesis (FTS), but is stable only at low-temperature. Here, the authors show that ε-Fe2C phase can be stabilized even at ~ 573 K by being encapsulated inside graphene layers, and retains high activity in FTS.

Exploring new multifunctional enzymes and understanding the mechanisms of catalytic promiscuity will be of enormous industrial and academic values. In the present study, we reported the discovery and characterization of a multifunctional enzyme BSGH13 from Bacillus subtilis BS-5. Remarkably, BSGH13 possessed α-amylase, endoglucanase, and xylanase activities. To our knowledge, this was the first report on an amylase from Bacillus species having additional endoglucanase and xylanase activities. Subsequently, we analyzed the effects of aromatic residues substitution at each site of the active site architecture on ligand-binding affinity and catalytic specificity of BSGH13 by a combination of virtual mutation and site-directed mutagenesis approaches. Our results indicated that the introduction of aromatic amino acids Phe or Trp at the positions L182 and L183 altered the local interaction network of BSGH13 towards different substrates, thus changing the multifunctional properties of BSGH13. Moreover, we provided an expanded perspective on studies of multifunctional enzymes.

Background This study aimed to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and its underlying mechanisms in human lung adenocarcinoma A549 cells in vitro. Methods 5FEM was obtained by the chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle, mitochondrial membrane potential (ΔΨm), scratch test, colony formation, and the expression levels of the key survivin pathway-related genes in A549 were evaluated. Results 5FEM could significantly inhibit A549 cell growth; induce cell apoptosis; increase G0/G1 population; reduce ΔΨm; inhibit cell migration and colony formation; upregulate caspase-9, P21, and Bax expression levels; and downregulate PARP, survivin, and Bcl-2 expression level. Conclusion These results enhanced our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.

Circulating tumor cells (CTCs) have been utilized in the diagnosis and prognosis of tumor. However, the CTC concentration is extremely low to be detected in peripheral blood. Many existing methods suffer from either expensive labeling or complex operation. In this study, we constructed a label- and enzyme-free and sensitive method to detect the breast cancer CTCs. First of all, a probe containing a breast cancer cell-specific aptamer and a complementary single-stranded DNA (trigger DNA P1) were designed. When the target cells are present, the aptamer binds to the CTCs and releases P1 which triggers the strand displacement amplification. This process generates three-way junction structure DNA, the specific translocation signals of which are identified by nanopore assay. The detection limit of tumor cells is 5 in the current experimental setup and can be further reduced. Furthermore, the method is demonstrated in a clinical sample test with high recovery rate and accuracy. Our results suggest that this method could be applied to early diagnosis of metastatic recurrence and prognosis determination.

Carboxylesterases have widely been used in a series of industrial applications, especially, the detoxification of pesticide residues. In the present study, EstC, a novel carboxylesterase from Streptomyces lividans TK24, was successfully heterogeneously expressed, purified and characterized. Phylogenetic analysis showed that EstC can be assigned as the first member of a novel family XIX. Multiple sequence alignment indicated that EstC has highly conserved structural features, including a catalytic triad formed by Ser155, Asp248 and His278, as well as a canonical Gly-His-Ser-Ala-Gly pentapeptide. Biochemical characterization indicated that EstC exhibited maximal activity at pH 9.0 (Tris-HCl buffer) and 55 °C. It also showed higher activity towards short-chain substrates, with the highest activity for p-nitrophenyl acetate (pNPA2) (Km = 0.31 ± 0.02 mM, kcat/Km = 1923.35 ± 9.62 s−1 mM−1) compared to other pNP esters used in this experiment. Notably, EstC showed hyper-thermostability and good alkali stability. The activity of EstC had no significant changes when it was incubated under 55 °C for 100 h and reached half-life after incubation at 100 °C for 8 h. Beyond that, EstC also showed stability at pH ranging from 6.0 to 11.0 and about 90% residual activity still reserved after treatment at pH 8.0 or 9.0 for 26 h, especially. Furthermore, EstC had outstanding potential for bioremediation of chlorpyrifos-contaminated environment. The recombinant enzyme (0.5 U mL−1) could hydrolyze 79.89% chlorpyrifos (5 mg L−1) at 37 °C within 80 min. These properties will make EstC have a potential application value in various industrial productions and detoxification of chlorpyrifos residues.

Background: This meta-analysis aimed to investigate the efficacy and safety of intravitreal injection of dexamethasone (DEX) in treating macular edema secondary to retinal vein occlusion. Method: PubMed, Embase-clinical key, clinicaltrials.gov, Web of Science, and SinoMed were searched to compare the application of DEX implant in patients with retinal vein occlusion secondary macular edema (RVO-ME). The central retinal thickness, best-corrected visual acuity (BCVA), postoperative intraocular pressure, and postoperative cataract were extracted. RevMan 5.3 was used to analyze and evaluate the data. Results: This study was based on six randomized trials. A total of 393 eyes were studied. DEX implant could effectively reduce macular edema caused by retinal vein occlusion. After 6 months, the drug could significantly improve the patients’ BCVA [95% confidence interval (CI), 9.669–21.649, P = 21.649]. At the same time, it also could significantly reduce the patients’ central retinal thickness (95% CI: 274.965–142.236, P = 0.0000). DEX implant could increase the intraocular pressure in some patients and greatly increase the risk of cataracts. Conclusions: DEX implant can effectively improve the BCVA of patients with RVO-ME, reduce the central thickness of the retina, and reduce the number of injections for a relatively long time. Therefore, intravitreal injection of DEX can be used as an effective method for treating RVO-ME.

Strong static electric fields can accelerate hydrate decomposition in pure water and induce the migration of ions (Na+ and Cl-) in salty water. The impact of Na+ and Cl- migration on hydrate decomposition under static electric fields deserve to be evaluated. Toward this goal, molecular dynamics (MD) simulations were conducted to investigate the effects of the migration of Na+ and Cl- induced by static electric fields on the decomposition behavior of methane hydrate. We find that the hydrate cages can be pierced and destroyed by the migration of Na+ and Cl- under static electric fields at least 0.9 V/nm at our conditions, thus causing hydrate decomposition. With increasing static electric field strength, the destructive ability of ions to hydrate becomes stronger and hydrate decomposition becomes faster. Moreover, detailed analysis shows that Na+ and Cl- can penetrate and pass through the hydrate block, and some ions concentrate on the surface of the hydrate block and cause hydrate decomposition. This work provides a new method for natural gas hydrate extraction and inhibition of hydrate formation in gas-oil pipelines. The hydrate is worth examining as a new ion exchange membrane material in the future due to the difference of ions migration velocity in hydrate.

In this study, it was found that methylcobalamin-C-10-Br (MeCbl-C-10-Br) from stinky tofu exerts an inhibitory effect on Listeria monocytogenes, and the minimum inhibitory concentration was 0.125 ng/mL. Here, we studied the effect of MeCbl-C-10-Br on the adenosylcobalamin (AdoCbl)-dependent enzyme glycerol dehydratase, the methylcobalamin (MeCbl)-dependent enzyme methionine synthetase and three types of vitamin B12 riboswitches from L. monocytogenes. The results show that MeCbl-C-10-Br inhibits about 100% of glycerin dehydrase activity and about 37% methionine synthase activity. While the expression of the downstream genes of the vitamin B12 riboswitch is suppressed, the ratios of inhibition of transport, synthetic, and functional vitamin B12 riboswitches from 1.00 μg/mL MeCbl-C-10-Br are approximately 60%, 30%, and 40%, respectively, which suggests that MeCbl-C-10-Br effectively controls the growth of L. monocytogenes. According to the results of the simulated fermentation, MeCbl-C-10-Br did not destroy the balance of intestinal microbes after ingestion, which indicates that MeCbl-C-10-Br is a safe antibacterial agent and can be applied to food in the future.

Patients with inflammatory bowel disease (IBD) are usually advised to supplement various types of vitamin B12, because vitamin B12 is generally absorbed in the colon. Thus, in the current study, the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on IBD symptoms will be investigated. Then, whether and how the application of various cobalamins would modify the taxonomic and functional composition of the gut microbiome in mice will be examined carefully. Dextran-sulfate-sodium-induced IBD mice were treated with MECBL or CNCBL; disease activity index (DAI) scores and intestinal inflammatory conditions of mice were evaluated. Fecal samples were collected; microbiota composition was determined with a 16s rRNA analysis; functional profiles were predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt); and short-chain fatty acids were measured. The consequence of higher relative abundances of Enterobacteriaceae and isomeric short-chain fatty acids by cobalamin treatment revealed that a high concentration of CNCBL but not MECBL supplementation obviously aggravated IBD. A microbial ecosystem rich in Escherichia/ Shigella and low in Lactobacillus, Blautia, and Clostridium XVIII was observed in IBD mice after a high concentration of CNCBL supplementation. In cobalamin-dependent enzymes, CNCBL was more efficient in the adenosylcobalamin system than MECBL and vice versa in the MECBL system. The distinct effects of various cobalamins were associated with the distribution and efficiency of vitamin-B12-dependent riboswitches. CNCBL had a strong inhibitory effect on all riboswitches, especially on btuB and pocR riboswitches from Enterobacteriaceae. CNCBL aggravated IBD via enhancing the proportion of Enterobacteriaceae organisms through riboswitch and enzyme systems. The present study provides a critical reference for offering a suitable amount and type of cobalamin during a symbiotic condition.