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Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA‐loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA‐ loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L‐type hydrogels are found to have preferable drug penetration over D‐type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration. [ABSTRACT FROM AUTHOR]

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self‐assembly mechanism. Two simple l/d‐phenylalanine‐based derivatives (L/DPFM) have been designed, and their solvent‐dependent morphology evolutions are illustrated. It was found that, as the content of H2O in aqueous ethanol solutions was increased, LPFM self‐assembles first into right‐handed nanofibers, then flat fibrous structures, and finally inversed left‐handed nanofibers. Assemblies in ethanol and H2O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology‐dependent cell adhesion and proliferation behaviors are further characterized. Left‐handed nanofibers are found to be more favorable for cell adhesion than right‐handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left‐handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left‐handed nanofibrous films, which indicates better flexibility. The difference in cell‐substrate interactions might lead to different effects on cell behavior. [ABSTRACT FROM AUTHOR]

Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade‐5‐I‐a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug‐resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics. Synopsis: The recent increase of human infections caused by invasive non‐typhoidal Salmonella, including Salmonella Livingstone, suggests their evolution towards niche adaptation to humans. This study reveals two novel subclades of S. Livingstone linked to human infections and mainly emerged in China. Genomic epidemiology showed imported animal feed was a major source of the early identified S. Livingstone in China, indicating international feed trading is a transmission route of this pathogen.Phylogeny of global Salmonella Livingstone isolates revealed five major clades of this pathogen, and clinical isolates from China largely belong to Clade‐5.Variabilities of stress responses were observed among isolates from distinct phylogenetic clades, with enhanced resistance to desiccation and diminished tolerance to oxidative stress for Clade‐5 isolates.Two novel subclades of Clade‐5 (i.e., C‐5‐I‐a/b) emerged in the last two decades and predominantly occurred in China accompanying the accumulation of antimicrobial resistance genes.The emerging clades showed significantly increased virulence in distinct animal models. i.e., chicken embryo, zebrafish embryo, and mice, indicating they have been undergoing evolution to adapt to humans. [ABSTRACT FROM AUTHOR]

As local anesthetics that are illegally added to cosmetics are harmful to consumer health, it is necessary to establish an efficient method for detecting these substances. Herein, a molecularly imprinted polymer (bupivacaine) was prepared by bulk polymerization and packed into a hollow fiber for use as an extraction phase to fabricate a membrane‐protected micro‐solid‐phase extraction device. The optimal values of the influencing parameters for the microextraction process were as follows: a sample solution pH of 9.0, a loading and washing time of 2 h, and an elution time of 32 min. A gas chromatography‐mass spectrometry method was established for the determination of local anesthetics and coupled with the microextraction method to successfully detect local anesthetics in cosmetic samples. The calibration curve for the proposed method was linear in the range of 0.4–50 mg/L and showed a good correlation coefficient (r2). The limits of detection for local anesthetics were in the range of 0.01–0.71 mg/L. The molecularly imprinted polymer exhibited good imprinting and selectivity, the micro‐solid‐phase extraction device was simple and inexpensive and fabrication was reproducible. The combination of molecular imprinting technology, membrane separation, and micro‐solid‐phase extraction methods used in this study can potentially be applied to pretreat local anesthetics in cosmetic samples. [ABSTRACT FROM AUTHOR]

Price and income elasticities are estimated for six food categories and different types of dairy across low‐, medium‐, and high‐income groups using 7426 urban households in Guangdong province from 2007 to 2009. Results from the estimation of a multistage budgeting approach to deal with zero expenditure show that demand for milk and dairy items among low‐income groups is more sensitive to income and price fluctuations compared to medium‐ and high‐income families. Therefore, a program of large income or price subsidies for dairy items may be an effective policy solution to improve the nutrition of the poor households. [EconLit citations: P46, Q18, O12]. Highlights: ●Consumption characteristic by income groups: Few studies have considered the gap of dairy consumption among different income groups, as different public policies may exert an influence on different income groups. It is of great significance for shortening income gap between different groups and stimulating sustainable economic growth.●Sample selection bias: The author considers the zero expenditure, one common problem in consumption. Heien and Wessells' two‐stage procedure is adopted in the third stage to remove the possible selection bias by zero consumption. The two‐stage feature of different types of dairy consumption—whether dairy products are purchased and the quantity—is considered. Thus, households with zero expenditure cannot be deleted, or else it will narrow the scope of samples and result in sampling bias.●Model selection: Wald test is conducted to judge whether linear or nonlinear demand system model is adopted through the null hypothesis testing that the joint parameter of quadratic term of total demand of dairy products is equal to zero. [ABSTRACT FROM AUTHOR]

Glucocorticoids have a certain whitening effect on the skin. However, frequent and long‐term use of cosmetics including glucocorticoids is harmful to health. Herein, we proposed a novel micro‐solid phase extraction method for the detection of prednisolone acetate, prednisone, and prednisolone in cosmetics coupled with high‐performance liquid chromatography. In this method, porous monolithic polymer micro‐extraction bars were prepared by "one‐step, one‐pot" in situ photopolymerization combined with sacrificial support in hollow fiber under water atmosphere. The crucial factors such as pH of sample solution, extraction, and elution times that influence micro‐extraction were optimized and found to be 9.0, 2 h, and 32 min, respectively. Under the optimum experimental conditions, the linear range of the calibration curves were from 5.0 to 2000 µg/L with correlation coefficients (R2) between 0.9922 and 0.9996. The limit of detection and limit of quantification were 1.5 µg/L and 5.0 µg/L, respectively, and the recoveries were found to be in range of 69.0–113.3%. The analysis of precision for intraday and interday were less than 10.40 and 10.59%. The device has been successfully achieved photopolymerization under water atmosphere. The results indicated that this method is simple, accurate, and satisfactory for the pretreatment and determination of glucocorticoids in complex cosmetics samples. [ABSTRACT FROM AUTHOR]

Abstract: Non‐alcoholic fatty liver disease (NAFLD) can progress to the more serious non‐alcoholic steatohepatitis (NASH), characterized by inflammatory injury and fibrosis. The pathogenic basis of NAFLD progressing to NASH is currently unknown, but growing evidence suggests MD2 (myeloid differentiation factor 2), an accessory protein of TLR4, is an important signalling component contributing to this disease. We evaluated the effectiveness of the specific MD2 inhibitor, L6H21, in reducing inflammatory liver injury in a relevant high‐fat diet (HFD) mouse model of NASH and in the palmitic acid (PA)‐stimulated human liver cell line (HepG2). For study, genetic knockout (MD2−/−) mice were fed a HFD or control diet for 24 weeks, or wild‐type mice placed on a similar diet regimen and treated with L6H21 for the last 8 or 16 weeks. Results indicated that MD2 inhibition with L6H21 was as effective as MD2 knockout in preventing the HFD‐induced hepatic lipid accumulation, pro‐fibrotic changes and expression of pro‐inflammatory molecules. Direct challenge of HepG2 with PA (200 μM) increased MD2‐TLR4 complex formation and expression of pro‐inflammatory and pro‐fibrotic genes and L6H21 pre‐treatment prevented these PA‐induced responses. Interestingly, MD2 knockout or L6H21 increased expression of the anti‐inflammatory molecule, PPARγ, in liver tissue and the liver cell line. Our results provide further evidence for the critical role of MD2 in the development of NASH and conclude that MD2 could be a potential therapeutic target for NAFLD/NASH treatment. Moreover, the small molecule MD2 inhibitor, L6H21, was an effective and selective investigative agent for future mechanistic studies of MD2. [ABSTRACT FROM AUTHOR]

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Acute inflammatory diseases are the leading causes of mortality in intensive care units. Myeloid differentiation 2 ( MD-2) is required for recognizing lipopolysaccharide ( LPS) by toll-like receptor 4 ( TLR4), and represents an attractive therapeutic target for LPS-induced inflammatory diseases. In this study, we report a chalcone derivative, L2H21, as a new MD2 inhibitor, which could inhibit LPS-induced inflammation both in vitro and in vivo. We identify that L2H21 as a direct inhibitor of MD-2 by binding to Arg90 and Tyr102 residues in MD-2 hydrophobic pocket using a series of biochemical experiments, including surface plasmon response, molecular docking and amino acid mutation. L2H21 dose dependently inhibited LPS-induced inflammatory cytokine expression in primary macrophages. In mice with LPS intratracheal instillation, L2H21 significantly decreased LPS-induced pulmonary oedema, pathological changes in lung tissue, protein concentration increase in bronchoalveolar lavage fluid, inflammatory cells infiltration and inflammatory gene expression, accompanied with the decrease in pulmonary TLR4/ MD-2 complex. Meanwhile, administration with L2H21 protects mice from LPS-induced mortality at a degree of 100%. Taken together, this study identifies a new MD2 inhibitor L2H21 as a promising candidate for the treatment of acute lung injury ( ALI) and sepsis, and validates that inhibition of MD-2 is a potential therapeutic strategy for ALI. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2 DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2 DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products ( AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57 BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (Ca MKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this study is to explore the determinants of urban at-home consumption demand for powdered milk in Guangdong province from 2007 to 2009. A double-hurdle model is used in this analysis based on survey data. The data include 8188 household distributed in 15 cities and prefectures of Guangdong province. Major findings show that the income growth of urban household, an increase in the level of education of the householder, and the different age groups within the household all have positive effects on urban at-home consumption demand for powdered milk. The prices of powdered milk have negative effects on milk consumption. Families in the Pearl River Delta consume more powdered milk than families in the other regions. The powdered milk consumption has not been significantly affected by the 2008 Chinese melamine tainted milk scandal. [ABSTRACT FROM AUTHOR]

T-cell factor/lymphoid enhancer factor (TCF/LEF) proteins regulate transcription by recruiting β-catenin and its associated co-regulators. Whether TCF/LEFs also recruit more factors through independent, direct interactions is not well understood. Here we discover Ring Finger Protein 14 (RNF14) as a new binding partner for all TCF/LEF transcription factors. We show that RNF14 positively regulates Wnt signalling in human cancer cells and in an in vivo zebrafish model by binding to target promoters with TCF and stabilizing β-catenin recruitment. RNF14 depletion experiments demonstrate that it is crucial for colon cancer cell survival. Therefore, we have identified a key interacting factor of TCF/β-catenin complexes to regulate Wnt gene transcription. [ABSTRACT FROM AUTHOR]

Chemical Oxygen Demand (COD), as a detection indicator of water pollution, is of particular importance in assessing organic pollution in water. Furthermore, accurate and simple measuring COD methods are essential for water quality assessment and pollution control. However, the photoelectrochemical oxygen demand (PECOD) measurement, as one of the measuring COD methods, is affected by the reaction of water splitting, which is one of the hindrances to the commercialization of the analytical method of the PeCOD measurement. Hence, to overcome this challenge, a new PANI/Ti:Fe2O3 photoanode is constructed by hydrothermal and photoelectrochemical (PEC) deposition methods and investigated their optical properties and photoactivity. Under optimization conditions, it is discovered that the oxidation of organic compounds produces a net steady‐state current (inet) is directly proportional to COD concentration, with a detection limit of 1 mM glucose solution and a wide linear detection range of 1–78.125 mM, which is suitable for high concentration of glucose detection. As has been noted, PANI/Ti:Fe2O3 photoanode overcomes the obstacles to the practical application and eventual commercialization of the PECOD technology. [ABSTRACT FROM AUTHOR]