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Non-fried whole-wheat instant noodles feature high dietary fiber and balanced nutrition but suffer from poor rehydration, texture, and flavor. This study aims to improve the quality of these noodles through mixed fermentation of yeast and lactic acid bacteria (LAB). The rehydration characteristics, textural profile, sensory quality, microstructure, volatile flavor compounds, and in vitro digestibility of non-fried instant whole-wheat noodles were evaluated. Yeast primarily reduced rehydration time and improved mouthfeel, whereas LAB mainly contributed to the formation of a continuous and uniform gluten network as well as the enhancement of noodle flavor. Moderate addition of the mixed culture (1% yeast + 0.05% LAB) promoted the construction of a homogeneous gluten network in non-fried whole-wheat instant noodles, effectively reducing starch digestibility and estimated glycemic index (eGI). However, excessive addition caused opposite effects on these noodles. This study provides an effective processing strategy for the production of high-quality, low-eGI whole-wheat instant noodles, which are suitable for people pursuing healthy diets and controlling blood sugar levels.

Aiming to improve the accuracy of path planning and autonomous positioning of the lidar tracking robot, the accurate tracking control of its moving trajectory is achieved. The trajectory of the lidar tracking robot is affected by the map location offset error, which leads to the low control accuracy. An improved particle swarm filter (PSO) algorithm is proposed to control the trajectory of a lidar tracking robot. The motion environment model of the lidar tracking robot is simulated and constructed, and the space coordinates of the lidar tracking robot are abstracted into the virtual world of particle swarm filter population. The tracking map grid model of the lidar tracking robot is obtained, and the target point is found by Particle Swarm filter evolution and the remote command control is carried out. An integral term of tracking error is designed on the synovial surface of the lidar tracking robot. The simulation results show that the algorithm is used to track the trajectory of the lidar tracking robot. The path offset correction ability is good and the control is stable.

The hot deformation characteristics of ductile iron are studied in the temperature range of 973 to 1273K and strain rate range of 0.001 to 1 s-1 by using hot compression tests.Processing maps for hot working are developed on the basis of the variations of efficiency of power dissipation with temperature and strain rate.The results reveal that the flow stress of ductile iron is sensitive to strain rate.In the processing map under strain of 0.7,a domain is centered at 1273 K and 1 s-1,and the maximum efficiency is more than 36%.According to the maps,the zone with the temperature range of 1173 to 1273 K and strain rate range of 0.1 to 1 s-1 may be considered as the optimum region for hot working.

The importance of tacrolimus in the treatment of myasthenia gravis （MG） as a substitute for corticosteroid-dependent immunosuppressive therapy is increasing. Thus far, however, no population pharmacokinetic （PopPK） analysis of tacrolimus in treating MG patients has been published. This article aimed to construct a PopPK model of tacrolimus for Chinese MG patients with the goal of improving its performance in MG treatment. A total of 253 trough concentration records were obtained from 83 Chinese MG patients. The effects of demographics, lifestyle and health status, biochemical test data, disease progression and treatment-related information （including co-administered medications） as covariates on the various parameters were investigated. The covariate selection was based on biological plausibility, clinical significance, statistical significance and reduction in inter-individual variability （IIV）. Bootstrap and normalized prediction distribution error （NPDE） analysis were performed to validate the final model. A one-compartment PopPK model with first-order elimination and a fixed absorption phase was constructed. The estimated apparent oral clearance （CL/F） and apparent oral volume of distribution （V/F） were 3.6 L/h and 1700 L, respectively, in the MG patients. Hematocrit and blood urea nitrogen were identified as two covariates that significantly influenced the CL/F. Immunoglobulin treatment （PRO） also had the potential to influence V/F, which was consistent with the clinical observations and the high protein-binding property of tacrolimus. Other covariates including age, weight, gender and co-administered medications had no obvious influence on CL/F or V/F. The first PopPK model of tacrolimus in MG patients was established. The identified covariates were of biological plausibility and clinical importance to help individualize the dosing schedule in MG patients.

Aim： Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer＇s disease （AD）. Huperzine A （HupA）, a natural inhibitor of acetylcholinesterase （ACHE）, is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Methods： Rat cortical neurons were treated with ferric ammonium citrate （FAC）, and cell viability was assessed with MTT assays. Reactive oxygen species （ROS） assays and adenosine triphosphate （ATP） assays were performed to assess mitochondrial function. The labile iron pool （LIP） level, cytosolic-aconitase （c-aconitase） activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified EIIman＇s method was used to evaluate AChE activity. Results： HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil （Don）, at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. Conclusion： We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect.

Background：At present,China has listed the compound tablet containing a fixed dose ofrosiglitazone and metformin,Avandamet,which may improve patient compliance.The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.Methods：This study was a 48-week,multicenter,randomized,open-labeled,active-controlled trial.Patients with inadequate glycaemic control （glycated hemoglobin [HbA1c] 7.5-9.5%） receiving a stable dose of metformin （≥1500 mg） were recruited from 21 centers in China （from 19 November,2009 to 15 March,2011）.The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.Results：At week 48,83.33% of patients reached the target of HbA 1 c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment,with significantly difference between groups.The target of HbAlc ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment.The target of fasting plasma glucose （FPG） ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment.The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment.Fasting insulin decreased 3.24 ±0.98 μU/ml from baseline in Avandamet treatment and 0.72 ＆#177; 1.10 μU/ml in uptitrated metformin treatment.Overall adverse event （AE） rates and serious AE rates were similar between groups.Hypoglycaemia occurred rarely in both groups.Conclusions：Compared with uptitrated metformin,Avandamet treatment provided significant improvements in key parameters ofglycemic control and was generally well tolerated.Registration number：ChiCTR-TRC-13003776.

Consumer indirect misbehavior in access-based consumption is a significant challenge for enterprises. The literature is in short of a deep understanding of the antecedent conditions of consumer indirect misbehavior in this context and limited by inconsistent findings, calling for developing a holistic and integrative theoretical framework. This study integrates three commonly used theoretical perspectives in the consumer misbehavior literature (i.e., deterrence, rational decision-making, and ethical decision-making) to present holistic archetypes of consumer indirect misbehavior formation. In accordance with this theoretical objective, we adopted an emerging approach for configurational analysis, i.e., fuzzy-set qualitative comparative analysis (fsQCA), to analyze the complex combinations of six influencing factors. We collected data using a scenario-based field survey of 264 experienced consumers of a popular bike-sharing service in China. The scenarios were developed based on relevant literature and a Delphi study. The fsQCA results reveal multiple configurations for high and low levels of consumer misbehavior intention. Specifically, perceived benefits and moral definition play important roles, while the effect of sanctions is highly dependent on other factors. These results lead us to derive three theoretical propositions for antecedent conditions leading to consumers' indirect misbehavior intentions in access-based consumption. This study enriches our understanding of the causes of misbehavior and provides novel insights for management practitioners to take appropriate countermeasures.

Mounting evidence has shown that side population (SP) cells are enriched for cancer stem cells (CSCs) responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-β and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-β. In conclusion, TGF-β-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-β-induced EMT may provide a novel strategy for preventing cancer progression.

Background Epithelial–mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. Methods BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. Results We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. Conclusions Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

The relationship between microstructure and mechanical properties of gas metal arc weld metal with strength over 890 MPa is discussed. The microstructure of the weld metals is characterized with OM, SEM, TEM and EBSD. The microstructure of the weld metals is mainly composed of martensite and bainite. Experimental results show that the microstructure with predominant fine lath bainite possesses good toughness of 77 .l, while its yield strength is less than 800 MPa. The microstructure of coarse lath martensite and bainite has the lowest toughness of 43 J and its yield strength is 820 MPa. The mixed microstructure with fine martensite, bainite and retained austenite films bears good combination of toughness and yield strength （62 J and 880 MPa, respectively）. It is concluded that fine effective grain size and ductile phase of austenite films are two main factors to achieve good mechanical properties.