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A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients. Here, we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials (SIL@T). SIL@T modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells, releasing silybin and oxaliplatin responsively in the cells. SIL@T preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals. Mechanistic studies have shown that SIL@T can effectively induce immunogenic cell death of metastatic cells, activate immune responses and increase infiltration of CD8+T cells. Meanwhile, the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed. This study demonstrates that SIL@T with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.

Compounds extracted from Ganoderma atrum(G. atrum) is significantly beneficial to human health, have been incorporated in numerous remedies owing to their brain and kidney health benefits and antiinflammatory and diuretic properties. G. atruma pilot of homology of medicine and food, has an important development value of functional food and health food. In this study, to develop a new ionic-liquid-based ultrasound-assisted extraction method and bio-affinity ultrafiltration coupled with LC and MS. Moreover, molecular docking was used to evaluate the activity of the AChE inhibitors, which were subsequently isolated and purified using consecutive counter-current chromatography (CCC) and semi-preparative high-performance liquid chromatography (HPLC). Lastly, the active compounds were identified using MS and nuclear magnetic resonance. Four AChE inhibitors, viz.ergosterol, ergosta-7,22-dien-3-one, ergosta-7-en-3β-ol, and ergosta-4,6,8(14),22-tetraen-3-one with purities of 92.23%, 90.19%, 90.52% and 96.72%, respectively, were obtained from G. atrumusing consecutive CCC (ethyl acetate/methanol/water, 4.0:1.0:7.0, v/v/v) coupled with semi-preparative HPLC (4% A (0–30 min), 4–100% A (30–40 min)). Our results suggested that G. atrumextracts can be used in the potential prevention and treatment of neurodegenerative diseases. It will help to elucidate the mechanisms of action of various medicinal plants at the molecular level and provide more opportunities to discover and develop new potential therapeutic remedies from health care food resources.

A new intervention was investigated for the induction of oral tolerance (OT) of OVA using narirutin by in vivoand in vitroexperiments combined with network pharmacology and structural analysis of molecular docking. Narirutin (and its metabolism naringenin) has effects on OT by affecting B cell function, DCs, and T cell response by prediction. It was verified that narirutin could affect B cell function of secreting antibodies, thereby reducing the ability of DCs to absorb antigens by affecting GATA3, CCR7, STAT5, and MHCII expression and regulating T cell response by suppressing Th2 and improving Treg cells in vivo. Molecular docking showed that steric hindrance effects may be the reason for weaker binding energy with targets of narirutin. However, this does not mean that it has no bioactivity, for it can inhibit mast cell degranulation. This finding is interesting because it offers the possibility of using natural compounds to promote oral tolerance.

Exploring novel polymerization mechanisms for the preparation of switchable isomers in chains from homopolymerization with only monomers is undoubtedly an exhilarating and challenging pursuit in polymer chemistry. Therefore, this work presents a novel strategy for realizing reversible cycle anion migrated ring-opening polymerization (AMROP) and general anionic polymerization (thermodynamics limits the further ring-opening reaction of the 1-cyclopropylvinylbenzene (CPVB) unit, and this process is defined as frustrated AMROP). By employing alkali metal alkoxides (potassium tert-butoxide (t-BuOK) and sodium 2,3-dimethylpentan-3-olate (NaODP)) as additives, the opening of the cyclopropyl group in CPVB can be controlled during homopolymerization. Additionally, the structure and sequence distribution of inserted CPVB units are determined by distinct selective polymerization mechanisms. Thus, the synthetic polymer includes two structural units, i.e., ring-opened CPVB (ro), which is generated from AMROP, and nonopened CPVB (ga), which results from frustrated AMROP (F-AMROP). Furthermore, in view of steric hindrance from the penultimate-unit effect during chain growth of CPVB, the process of F-AMROP cannot continuously occur and requires the AMRO process of CPVB to decrease the steric hindrance around active centers. Therefore, under the influence of steric hindrance from the penultimate unit, AMRO, and thermodynamics, a reversible cycle of frustrated and nonfrustrated AMROP can be activated during the polymerization process, which further realizes a single monomer to prepare an alternating polymer with different isomers. Ultimately, the mechanisms for AMROP and F-AMROP are explored deeply with density functional theory calculations. This intriguing mechanistic finding will become a pioneering and innovative strategy for development of polymerization mechanisms and unprecedented polymer structures in polymer synthesis.

N6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.

Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other. Therefore, we reported the design of a pH-sensitive drug delivery system that targets different cells in TME successively. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria were applied to coload paclitaxel (PTX) and regulated in development and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs could first release PTX triggered by the tumor pH (pH 6.8). Then the rest of it would be taken in by M2 macrophages to increase their level of glycolysis. Great potential was observed in TAM repolarization, tumor suppression, tumor immune activation, and TME remolding in the triple-negative breast cancer model. The application of the OMV provided an insight for establishing a codelivery platform for chemical drugs and genetic medicines.

Five novel biscembranoids, ximaolides H–L (1–5), were isolated from the Hainan soft coral Sarcophyton tortuosum. Compounds 1and 2are the first examples of biscembranoids bearing a 135-bridged lactone moiety, 4is the first biscembranoid comprising an uncommon oxetane ring, and 5represents the first 36-peroxyl biscembranoid.

As a rapid proliferating tissue, tumor cells have to optimize nutrient utilization to withstand harsh conditions. Several approaches have been explored to inhibit the growth and metastasis of tumor by disrupting the reprogrammed tumor metabolism. However, nutrient limitations within solid tumors may induce the metabolic flexibility of malignant cells to sustain growth and survival using one nutrient to fill metabolite pools normally supplied by the other. To overcome this predicament, a promising click-nucleic-acid-containing platform for codelivery of rapamycin, anti-PFKFB4 siRNA, and targeting ligand aptamer AS1411 was applied. PFKFB4 could act as a promising target for tumor therapy for being a molecular fulcrum that could couple glycolysis to autophagy by promoting aggressive metastatic tumors. The downregulation of PFKFB4 can help inhibit the SRC3/Akt/mTOR pathway, leading autophagy to the direction of promoting apoptosis of tumor cells, which is induced by the collapse of tumor cellular homeostasis, while low dosages of rapamycin could decrease surgery-induced immune dysfunction. Enhanced tumor autophagy, favorable in vivo antitumor efficacy, and effective systematic immune activation are observed after treatment, suggesting that autophagy and glycolysis can serve as an integrated target for tumor treatment.

Aberrant energy and substance metabolic pathways of tumor cells critically support tumor cell proliferation by hijacking the resources from nonmalignant cells, thereby establishing a metabolite flow favorable to tumor progression. This metabolic adaptation of tumor cells further modulates the immune landscape, ultimately creating a tumor microenvironment characterized by drug resistance and immunosuppression. The synergistic regulation of energy and substance metabolic pathways might be a good antitumor therapeutic paradigm. However, due to the metabolic convergence, it is crucial to selectively modulate the aberrant metabolism of tumor cells without compromising the functionality of other cells. Small-molecule drugs have the ability to target a wide range of biomolecules for antitumor therapy, but their application is limited by undesirable toxicities. Constructing nanodrug delivery systems can improve their properties and allow for the inclusion of multiple drugs, thereby exerting synergistic antitumor effects. In this study, we developed a two-drug codelivery system using drugs-conjugated multibranched polymers to modulate tumor cell metabolism by exploiting synthetic lethal pathways for safe and effective antitumor therapy. By delivery of adapalene and erastin simultaneously through nanoparticles, the material and energy metabolism of tumor cells can be regulated. This nanoparticle construction achieves tumor tissue targeting and responsive drug release, alters metabolite flow within tumor cells, and effectively kills tumor cells. Additionally, the nanoparticles can reverse the tumor immunosuppressive microenvironment, starting from single-cell regulation to whole-lesion control.

Both polymethylmethacrylate (PMMA) and traditional calcium phosphate–based cements have some deficiencies as augmentation materials for pedicle screw fixation. Here, a novel calcium phosphate–based nanocomposite (CPN) for the augmentation of pedicle screw fixation was developed based on previous study, and the handling properties, biomechanical performance, and biodegradation behaviour of CPN were evaluated and compared with clinical PMMA by means of a cadaver study and animal tests.

Research about DNA composition has been concentrated on DNA damage in the past few decades. However, it still remains a great challenge to construct a rapid, facile, and accurate approach for simultaneously monitoring four DNA bases, guanine (G), adenine (A), thymine (T), and cytosine (C). Herein, a novel electrochemical sensor based on phenanthroimidazole derivative, 2-(4-bromophenyl)-1-phenyl-1H-phenanthro[9,10-d]-imidazole (PPI), is successfully fabricated by a simple electrochemical method. The bromophenyl group in PI could expand their aromatic plane, induce the π-conjugated extension, and enhance the charge transfer and π–π interaction. The phenyl group at N1 position could regulate the intermolecular interaction, which could promote the possibility of intermolecular connection. The PPI polymer (poly(PPI)) with π-electron enriched conjugation architecture has been applied in simultaneous determination of G, A, T, and C in neutral solution by square wave voltammetry (SWV) method with well-separated peak potentials at 0.714, 1.004, 1.177, and 1.353 V, respectively. The sensor functionalized with poly(PPI) exhibits wide linear response for G, A, T, and C in the concentration ranges of 3–300, 1–300, 30–800, and 20–750 μM, respectively. With favorable selectivity, stability, and reproducibility, the sensor is successfully utilized to monitor four DNA bases in real samples, displaying a promising prospect for electrochemical sensing devices.

ABSTRACTCardiotocography (CTG) is the basic method of monitoring foetal condition in the perinatal period. However, due to the limited insight into the CTG generation mechanism, some CTG recordings can be mistreated as a predictor of neonatal asphyxia, leading to a wrong assessment of the foetal status and improper obstetric intervention. Therefore, in case of suspicious CTG indications, a reliable verification of the true foetal status is vital for reducing the clinical diagnosis false-positive rate and avoiding the unnecessary obstetrician intervention. The paper presents the results obtained for 44 foetuses on the shares of three heart rate variation (HRV) ranges and quiet sleep cycles. This approach uses the parameters of the HRV range shares and quiet sleep cycles to analyse different types of foetuses. The results obtained show that most parameters reveal significant differences between normal and suspicious groups. This is quite lucrative for defining a set of coefficients, whose incorporation into a classifier will improve the accuracy of distinguishing the normal foetuses from suspicious ones.

Ginseng(Panax ginsengC. A. Mey.) is a traditional medicinal herb in Asia. Studies have shown that gin-senosides significantly affect immunoregulation and rare ginsenosides have anti-allergic effects. In this research, a high temperature and high pressure method was utilized to increase the contents of rare ginsenosides in the ginseng extract(GE). The anti-allergic effects of this extract were investigated in vivo. Water was used as the extraction solvent in extracting the rare ginsenosides viathe high temperature and high pressure method. Extraction time and temperature were investigated in order to increase the contents of rare ginsenosides. Rare ginsenosides were qualitatively analyzed by HPLC-ESI-MS and quantitatively analyzed by HPLC-UV. Anti-allergic effects of the extracts were assessed using the ovalbumin(OVA)-induced allergic asthma model in vivo. An extraction temperature of 145 °C and extraction time of 2.0 h were chosen as the optimal conditions. Compared with traditional method, the contents of total rare ginsenosides extracted were considerably higher using the new method, that is, 14.74 times that extracted by the traditional method. In our in vivoexperiments, treatment with high concentration GE may have anti-allergic effects in decreasing the total amount of IgE in serum and IL-4 in bronchoalveolar lavage fluid(BALF), and in improving the ratio of CD4+to CD8+T cells. The high temperature and high pressure method was an effective method to obtain GE containing more rare ginsenosides, which maybe become anti-allergic agents.

Two new steroidal saponins(2, 3) and two known compounds(1, 4) were isolated from 75% ethanol extract of Allii macrostemonisbulbus by various spectral methods. The two new steroidal saponins were respectively elucidated as (25S)-26-O-β-D-glucopyranosyl-5α-furostanol-2α,3β,22,26-tetrol-3-O0-β-D-glucopyranosyl(1→2)-[β-D-glucopyranosyl(1→3)]-β-D-glucopyranosyl(1→4)-β-D-galactopyranoside(2) and 26-O-β-D-glucopyranosyl-5α-furostanol-25(27)-ene-3β,22,26-tetrol-3-O-β-D-glucopyranosyl(1→2)-[β-D-glucopyranosyl(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(3). Compound 4was obtained from this medical plant for the first time. The activity experiments of proliferation inhibition on tumor cells were performed by cell counting kit-8(CCK-8) method for compound 2(25S-configuration) and its isomer(compound 1, 25R-configuration). The results show that compounds 1and 2have weak inhibition on lung cancer A549 cells, melanoma A375 cells and breast cancer MCF-7 cells as well as certain inhibitory effect on liver cancer HepG2 cells, and the inhibitory effect of compound 1 is stronger than that of compound 2.

Two new baccharane-type glycosides (1and 2), together with seven known baccharane-type glycosides (3―9) hosenkoside A, hosenkoside B, hosenkoside C, hosenkoside F, hosenkoside M, hosenkoside K and hosenkoside G were isolated from the dried seeds of Impatientis balsaminaL. The new baccharane-type glycosides were identified as honsenkol A-3-O-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl-O-β-D-glucopyranosyl(1) and (3S,4R,17R,20S)-17-hydroxy-3-O-β-D-xylopyranose(12)-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl-21,24-epoxybaccharane(2), respectively, by spectroscopic methods, including NMR(1D and 2D), IR and HR-ESI-MS. Compounds 1and 2were evaluated for in vitroinhibitory activity against the cell lines. Compound 2with a new baccharane skeleton had anti-hepatic fibrosis activity against A375 cells in bioassay results, which means the new compounds have potential value in antitumor applications.

A novel storage and extraction method was developed for biofluids. Plasma spiked with four types of minor ginsenosides (Rg2, Rg3, Rh1and Rh2) was used as a model biofluid to evaluate this method. The method was based on solid-phase adsorption and ultrasonic-assisted nebulization coupled with solid phase extraction (SPA-UANE-SPE). Diatomaceous earth was used as an adsorbent to store the plasma for long periods of time at room temperature. Ultrasonic-assisted nebulization system-solid phase extraction was used to extract the four minor ginsenosides from the plasma. Some experimental parameters, such as the type and amount of the adsorbent, the ultrasonic-assisted nebulization extraction time, the pH of the extraction solution, the concentration of ZnSO4, the amount of C18, and the type and volume of the eluent were investigated and optimized. Under the optimized conditions, the recoveries of four minor ginsenosides were in the range of 78.5–91.4%, and the RSDs are in the range of 3.5–4.4%. For the storage stability test, the stability of the method was better than that of 4 °C storage and was similar to that of −20 °C storage. Compared with other methods, the proposed method had a better extraction performance and was advantageous in terms of ease of operation, stable long term storage, and minimal requirements for storage conditions. Thus, this method may be effective for sample preparation in biofluid analysis.

Eight polycyclic furanobutenolide-containing norcembrane diterpenoids featuring C19 frameworks (1–8) were rapidly recognized and isolated from the Hainan soft coral Sinulariasp. by the HSQC-based small molecule accurate recognition technology. Yonarolide A (1a), featuring an unprecedented 5/6/4/4/7 pentacyclic ring skeleton, was surprisingly obtained as a transformed product by leaving compound 1under indoor natural light, and was further proved to be a [2 + 2] cycloaddition product of 1by photochemical reaction. The absolute stereochemistry of 1aand the three known norcembrane diterpenoids 1, 4, and 7were determined by using X-ray diffraction (XRD) analyses. Further, with the aid of XRD analysis, the structure of scabrolide B (2), which was previously reported of possessing 5/6/7 tricyclic skeleton, was firmly revised as 2awith the rare inelegane skeleton featured by the highly oxygenated 5/7/6 tricyclic carbocycle.

A new triterpenoid glycoside(1) and seven known triterpenoid glycosides, pseudoginsenoside RT2(2), yesanchinoside R2(3), vinaginsenoside R13(4), vinaginsenoside R8(5), notoginsenoside E(6), 6′′′-O-acetylginsenoside Re(7), 6″-O-acetylginsenoside Rb1(8), were isolated from the rhizomes of Panacis majoris. The new triterpenoid glycoside was elucidated as 3-O-[β-D-glucopyranosyl-(1→2)-β-D-(6′-O-ethyl)-glucuronopyranosyl]-oleanolic acid-28-O-β-D-glucopyranoside by extensive spectroscopic and phytochemical methods. Compounds 2―8were obtained from the plant for the first time. Compounds 3and 4displayed good activities against adenosine diphosphate (ADP)-induced platelet aggregation, and compounds 1, 5, 6and 8showed moderate activities. Compound 6exhibited moderate antiplatelet aggregation activity induced by arachidonic acid(AA).

Rare ginsenosides in Panax quinquefoliusL. have strong bioactivities. The fact that it is hard to obtain large amounts of rare ginsenosides seriously restricts further research on these compounds. An easy, fast, and efficient method to obtain different kinds of rare ginsenosides simultaneously and to quantify each one precisely is urgently needed.

Food allergy has become a worldwide problem. To find an effective way to reduce the allergic effect of allergen is an interesting topic. In this work, the interaction between ovalbumin(OVA) and tangeretin was studied by means of spectroscopy, molecular docking calculation and animal experiment. As the results show, static quenching of fluorescence intensity happened due to the interaction between OVA and tangeretin. Binding constants, binding sites, and thermometric parameters were obtained. The conformation changing of OVA occurred due to the interaction between it and tangeretin. The molecular docking calculation results show that the epitopes Arginine 84(ARG84), Leucine 87(LEU87), Asparagine 88(ASN88), Serine 103(SER103), Arginine 104(ARG104), Leucine 124(LEU124), Arginine 126(ARG126), Glycine 127(GLY127), Glycine 128(GLY128) and Tryptohan 148(TRP148) of OVA were occupied by tangeretin after the docking, which means tangeretin may have some inhibition effects. As the results of animal experiments, the amount of IgE and lung tissue sections of female BALB/c mice in different groups show that tangeretin with different concentrations has better effects than dexamethasone. In conclusion, the tangeretin may have the effects to reduce the allergic effects of OVA via occupying the IgE-binding epitopes of OVA.

Many cities with metro systems are experiencing overcapacity problems on some or many lines. Beijing is one such city whose metro also services a high proportion of short-distance trips. The proportion of short-distance travel—less than 5 km (3.1 mi)—carried out on foot or on bicycle varies greatly across cities, depending on alternative travel modes and local environmental conditions. In this study, users of a multimodal transportation corridor that included metro (n= 400) were interviewed about their travel mode preferences depending on distance within the short-distance travel category. Users were also asked to state their preferences for mode, depending on distance and a progressive rise in metro ticket fare. Finally, users were asked to state their mode preferences for trips that extended to five metro stations if a public bicycle system with a separate lane were made available. Modal choice was highly sensitive to variable short-distance trips. A progressive shift to bus use occurred as the metro fare price increased, with little change in the walking rate or in the use of motorized modes. When the original low metro fare price was maintained, the availability of a public bicycle system led to a sevenfold increase in bicycle use, with significant drops in bus share, and to a lesser extent, metro share. Responses to the stated preference survey indicated that fares and a public bicycle program might be effective to manage the use of metro for short-distance trips.

With the oxidation treatment, eighteen compounds were separated from 20(S)-ginsenoside Rg2, Rh1, protopanaxatriol(PPT) and their 20(R)-epimers in total and cytotoxicity of most of them was evaluated against three human cancer cell lines HeLa, A549 and MCF-7 by 3-(4,5-dimetylthiazol-z-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Their structures were confirmed by means of nuclear magnetic resonance(NMR) and mass spectrometry and the results were compared with those of previous literature. In this study, we systematically semisynthesized all four ocotillol type saponins, i.e., (20S, 24S), (20S, 24R), (20R, 24S) and (20R, 24R). All the configurations at C20 kept the same with their starting materials. Meanwhile a pair of C24 epimers was generated in terms of ocotillol type saponins. In addition, seven compounds(4―8, 13and 14) were reported firstly. The cytotoxic results distinguished the ocotillol type products(6, 7, 13and 14) from 20(R)-PPT and 20(R)-ginsenoside Rh1, which possessed better cytotoxicities than their correspondents from 20(S)-epimers against HeLa cells, and the carbonyl group at C3 can improve the cytotoxicity, which helped us to gain deeper insight into Ocotillol type saponins.

A rapid and effective sample pretreatment method, dispersant-assisted dynamic microwave extraction, was first applied to the extraction of six triazine herbicides from rice. The dynamic microwave extraction was coupled with matrix solid-phase dispersion (MSPD). The dispersant in MSPD was used to disperse the sample and adsorb impurities. Microwave irradiation was used to promote the transfer of the analyte and accelerate the extraction. The extraction and clean-up were performed simultaneously. The effects of experimental parameters, including the solvent type, volume of the extraction solvent, microwave power, type of dispersant, mass ratio of dispersant to rice, and flow rate of the extraction solvent, on the recoveries of the analytes were investigated. The limits of detection for the analytes ranged from 0.62 to 1.79 μg kg−1. The recoveries of the triazine herbicides in spiked rice samples were in the range of 84.3–101%, and the relative standard deviations were lower than 6.2%.

A green and effective extraction system based on the use of an ultrasound-assisted ionic liquid aqueous two-phase system (IL-ATPS) was developed for the determination of aconitum alkaloids in lateral roots of Aconitum carmichaeliDebx (Fuzi in Chinese). IL-ATPS parameters, including the type and amount of ionic liquid, amount of salts, and pH value, as well as extraction time, were investigated. Under the optimized conditions, the recoveries of the analytes varied from 80.37 to 107.18%. The detection limits and quantification limits for the analytes were achieved within the ranges of 0.048–0.082 μg g−1and 0.16–0.30 μg g−1, respectively. After extraction, the recovery of ionic liquids without the use of organic solvents was also confirmed. The hydrophilic ionic liquids (1-hexyl-3-methylimidazolium bromide) were converted into hydrophobic ionic liquids (1-hexyl-3-methylimidazolium hexafluorophosphate) by a metathesis reaction, and in situliquid–liquid microextraction was triggered simultaneously. Finally, 0.1 mol L−1HCl aqueous solution (containing 5% Tween-20) was used as the back-extraction agent to recover the ionic liquids.

Many cities with metro systems are experiencing overcapacity problems on some or many lines. Beijing is one such city whose metro also services a high proportion of short-distance trips. The proportion of short-distance travel—less than 5 km (3.1 mi)—carried out on foot or on bicycle varies greatly across cities, depending on alternative travel modes and local environmental conditions. In this study, users of a multimodal transportation corridor that included metro (n= 400) were interviewed about their travel mode preferences depending on distance within the short-distance travel category. Users were also asked to state their preferences for mode, depending on distance and a progressive rise in metro ticket fare. Finally, users were asked to state their mode preferences for trips that extended to five metro stations if a public bicycle system with a separate lane were made available. Modal choice was highly sensitive to variable short-distance trips. A progressive shift to bus use occurred as the metro fare price increased, with little change in the walking rate or in the use of motorized modes. When the original low metro fare price was maintained, the availability of a public bicycle system led to a sevenfold increase in bicycle use, with significant drops in bus share, and to a lesser extent, metro share. Responses to the stated preference survey indicated that fares and a public bicycle program might be effective to manage the use of metro for short-distance trips.

Background: Inorganic nanocomposites especially Au nanostructures have exhibited outstanding physicochemical properties in biomedical fields. For further clinical applications on theranostics, especially drug delivery, numerous explorations of green and facile synthesis methods combining with pharmacoactive natural components have been investigated to construct safe and multifunctional bioactive Au nanoparticles (NPs). Ginsenoside Rh2is protopanaxadiol type compound isolated from plants of genus Panax, with excellent anticancer effect and antioxidant activity. In this research, we prepared the novel Au nanoparticles using ginsenoside Rh2as both reducing and stabilizing agents. Results: The synthesized Au@ginsenoside Rh2NPs were proved to exhibit desirable inhibitory effect on different cancer cell lines, which benefited from the inherent anticancer effect of the ginsenoside Rh2. Investigations in vitro indicated that Au@ginsenoside Rh2NPs inhibited cell proliferation, cell migration and invasion, induced cell cycle arrest, enhanced the reactive oxygen species (ROS) generation, and regulated the protein expressions of caspase-3, 8, 9 to trigger cell apoptosis as well. Conclusions: Because of the absence of toxic chemical surfactants, the eco-friendly synthesis method of Au NPs modified by natural phytochemicals avoided tedious separation and modification processes. On the other hand, Au@ginsenoside Rh2NPs also improved water solubility and bioavailability of the hydrophobic drug ginsenoside Rh2. It broadened minds for preparation and application of traditional Chinese medicines (TCMs) modified metal nanoparticles and deserved further study.

DNA methylation plays vital roles in both prokaryotes and eukaryotes. There are three forms of DNA methylation in prokaryotes: N6-methyladenine (6mA), N4-methylcytosine (4mC), and 5-methylcytosine (5mC). Although many sequencing methods have been developed to sequence specific types of methylation, few technologies can be used for efficiently mapping multiple types of methylation. Here, we present NT-seq for mapping all three types of methylation simultaneously. NT-seq reliably detects all known methylation motifs in two bacterial genomes and can be used for identifying de novo methylation motifs. NT-seq provides a simple and efficient solution for detecting multiple types of DNA methylation.

In this work, reduced graphene oxide coated with ZnO (RGO–ZnO) nanocomposites was synthesized by a hydrothermal reduction strategy. The presence of ZnO was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subsequently, RGO–ZnO was used as a dispersive solid-phase extraction (DSPE) sorbent for the enrichment of eight organophosphorus pesticides (OPs) in apple, cucumber and water samples prior to their determination by gas chromatography-mass spectrometry (GC-MS). Several experimental parameters affecting the extraction efficiencies, including the amount of RGO–ZnO, extraction time, and the pH of the sample solution, as well as the type and volume of eluent solvent, were investigated and optimized in this work. Under the optimal experimental conditions, good linearity existed in the range of 0.5–200.0 ng g−1for all the analytes with the correlation coefficients (R2) ranging from 0.9894 to 0.9983. The limits of detection (S/N= 3) of the method for the compounds were between 0.01 and 0.05 ng g−1. Good reproducibilities were acquired with the relative standard deviations (RSDs) below 8.6% for both intra-day and inter-day precision. The recoveries of the method were in the range of 75.0% to 104.2%.

The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II)2‐AMD3100 (AMD‐Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long‐term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells. The finding indicated that the imGEL can regulate the immune microenvironment, inhibit GBM recurrence, and gain valuable time for subsequent adjuvant clinical chemotherapy. Based on the current clinical dilemma of glioblastoma, this study describes a simple and mild postoperative local treatment strategy with clinical transformation prospects. Specifically, it is an injectable hydrogel system with the function of regulating the immune post‐operative micro‐environment to kill the residual tumor cells in the empty window period, which has gained valuable time for subsequent adjuvant treatment.

The present study demonstrated that an omega (n)-3 fatty acid, ethyl-eicosapentaenoic acid (ethyl-EPA), supplemented diet significantly attenuated the stress/anxiety behavior of rats in the "open field" and elevated plus maze, which was induced by subchronic intracerebroventricular administration of proinflammatory cytokine interleukin (IL)-1beta. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-gamma-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1beta administration, ethyl-EPA reduced the elevated prostaglandin (PG) E2 secretion and increased the secretion of antiinflammatory cytokine IL-10 from whole blood cells. Ethyl-GLA showed a similar antiinflammatory effect to ethyl-EPA. By contrast, n-6 fatty acid arachidonic acid (AA) had no effect on the behavior, immune, and endocrine changes induced by IL-1. AA alone enhanced the basal inflammatory response, raised serum corticosterone concentrations, and induced anxiety behavior in the elevated plus maze. The reduced growth rates of rats following the administration of IL-1 was attenuated by ethyl-EPA, and to a greater extent by ethyl-EPA plus ethyl-GLA, but not by AA alone or in combination with ethyl-EPA. Thus, ethyl-EPA would appear to antagonise the endocrine, immune, and behavioral effects of subchronic IL-1 administration. Ethyl-GLA only antagonised IL-1-induced inflammatory changes, whereas AA caused an increase in the secretion of corticosterone and PGE2, and induced anxiety-like behavior without enhancing the effects of IL-1.

Well-tailored construction of liquid crystal networks (LCNs) with simultaneous molecular mobility and mechanical enhancement is desirable. Since the properties of polymeric materials are largely a result of the molecular compositions of polymer chains, in the present work, we demonstrate the tuning compositional synthesis of anionically polymerized random styrene-butadiene rubbers (r-SBRs) with well-controlled 75 wt % butadiene (Bd) contents that offer molecular mobility. Microstructural 1,2-olefins of 51.5–64.0 mol % were designed to attach 50 mol % SiH-terminated mesogenic moieties (M) along Bd units using hydrosilylation. As mechanical strength usually conflicts with high molecular mobility, an integrated design derived from the orderly LC stacking and simultaneous crosslinking in various ratios of the dynamic 2(6-isocyanatohexylaminocarbonylamino)-6-methyl-4[1H]-pyrimidinone (UPy-NCO) and permanent hexamethylene diisocyanate (HMDI) along 1,4-olefins of Bd units offers necessary mechanical strength and molecular mobility, resulting in a series of dynamic LCNs (r-SBR-g-[M·HMDI·UPy]). LC textures, phase transitions, self-healing/welding, and shape memory capacities were comprehensively studied. All LCNs showed LC textures in POM around Ti(42–53 °C), which definitely contributed to both mechanical performance and molecular mobility due to the 50 mol % orderly LC stacking. Ureidopyrimidinone (UPy) that forms a dynamic H-bond is beneficial for the temporary shape fixity ratio (Rf), recyclability, and self-healing/welding ability while decreasing the shape recovery ratio (Rrec) because UPy can increase breaking elongations but sacrifice the mechanical strength. However, HMDI that forms a covalent crosslink showed the contrary effect, as HMDI can effectively enhance the mechanical strength but reduce the chain mobility. It is evidenced that r-SBR45k-g-[M-0%, 2%] can hardly undergo shape recovery (Rrec= 0) despite Rf= 92.6%, while with regard to r-SBR45k-g-[M-10%, 2%], Rrecgreatly increased to 100%, but Rfdecreased to 46.2%. All LCNs showed a higher than 82% self-healing/welding efficiency, with an exception of r-SBR-g-[M-10%, 2%]. This indicated the cooperative effect of molecular compositions on the properties. The well-tailored construction of polymer chain architecture through quantitative synthesis proves to be a powerful strategy for manipulating properties.