Enhancement of hybrid organohydrogels by interpenetrating crosslinking strategies for multi-source signal recognition over a wide temperature range.

With substantial temperature differentials between summer and winter in polar regions, there exists a pressing necessity for flexible sensors capable of functioning across a broad temperature spectrum to facilitate the construction of a more intelligent human-machine interface. Nevertheless, developing flexible sensors resilient to extremely low temperatures remains a significant challenge. In this study, we present an organohydrogel capable of functioning ranging from ambient to -78 °C, enabling real-time monitoring of multi-source signals, including motion, physiology, speech, and pressure. We synthesize organohydrogel employing a singular methodology: interpenetrating network structures as matrix frameworks, dynamic hydrophobic linkages as the physical cross-linking points, and incorporating a bionic binder. H-Bonding and chain entanglement synergistic supramolecular interactions build the organohydrogel matrix with microphase-separated domains, which, together with the combination of binary solvents and inorganic salts, allows it to exhibit excellent properties, including large stretchability (≈1700%), high ionic conductivity (1.57 S m-1), admirable sensing sensitivity performance (gauge factor: GF = 6.47, S = 0.32 kPa-1), an exceptionally low-pressure detection threshold (≈1 Pa), enables wireless transmission of distress signals through human-machine interaction even at -78 °C, which makes it possible to use it in polar exploration and to give robots a "sense of touch" for a variety of deep-diving tasks.

Efficacy and Safety of Methylprednisolone Pulse Therapy and Conventional Oral Prednisone for Pediatric Patients With Nephrotic Syndrome.

Context: High-dose methylprednisolone pulse therapy and oral high-dose prednisone are two common treatments for pediatric nephrotic syndrome (NS). While both treatments have shown effectiveness for patients with pediatric NS to some extent, a clear comparison of their efficacy and safety remains elusive, posing a challenge for clinicians when devising treatment plans. Objective: The study intended to compare the efficacy and safety of high-dose methylprednisolone pulse therapy and conventional oral high-dose prednisone for pediatric patients with NS, to provide more accurate treatment recommendations for clinicians to optimize their treatment plans, improve their QoL, and prevent complications. Design: The research team conducted a randomized controlled trial. Setting: The study took place at the Second Affiliated Hospital of Fujian Medical University in Quanzhou, China. Participants: Participants were 60 patients with pediatric NS who received treatment at the hospital between November 2020 and March 2022. Interventions: The research team randomly divided participants into two groups, each comprising 30 patients: (1) the intervention group, which received high-dose methylprednisolone pulse therapy, and (2) the conventional group, which received oral high-dose prednisone. Outcome Measures: The research team measured: (1) clinical efficacy rates, the primary outcome measure; (2) time to symptom relief; (3) laboratory indicators, including blood urea nitrogen (BUN), serum creatinine (SCr), serum globulin (GLB), and 24-hour urine protein quantification; and (4) incidence of adverse events. Results: Compared to the conventional group, the intervention group's: (1) clinical efficacy rate was significantly higher (P < .05); (2) resolution times for edema (P < .001) and urine protein turning negative (P < .001) were significantly shorter; (3) levels of BUN (P < .001), SCr (P < .001), GLB (P < .001), and 24-hour urine protein quantification (P < .001) were significantly lower; and (4) incidence of adverse reactions was significantly higher (P < .001). Conclusions: High-dose methylprednisolone pulse therapy demonstrated better efficacy in treating pediatric NS patients, showing a shorter time to symptom relief, but it may also entail a higher risk of adverse reactions compared to conventional oral high-dose prednisone. Clinicians should consider the specific circumstances and needs of pediatric patients when selecting a treatment.

Brain development mediates the relationship between self-reported poor parental monitoring and adolescent anxiety.

Adolescence is the peak period for the onset of generalized anxiety disorder (GAD). Brain networks of cognitive and affective control in adolescents are not well developed when their exposure to external stimuli suddenly increases.Reasonable parental monitoring is especially important during this period.To examine the role of parental monitoring in the development of functional brain networks of GAD, we conducted a cross-validation-based predictive study based on the functional brain networks of 192 participants. We found that a set of functional brain networks, especially the default mode network and its connectivity with the frontoparietal network, could predict the ages of adolescents, which was replicated in three independent samples.Importantly, the difference between predicted age and chronological age significantly mediated the relationship between parental monitoring and anxiety levels. These findings suggest that inadequate parental monitoring plays a crucial role in the delayed development of specific brain networks associated with GAD in adolescents. Our work highlights the important role of parental monitoring in adolescent development.

Disruptions of salience network during uncertain anticipation of conflict control in anxiety.

BACKGROUND: Anxiety has been characterized by disrupted processing of conflict control, while little is known about anticipatory processing of conflicts in anxiety. Anticipation is the key factor in both anxiety and cognitive control, especially under uncertain conditions. The current study therefore examined neurocomputational mechanisms of uncertain anticipation of conflict control in anxiety. METHODS: Twenty-six participants with high-trait anxiety and twenty-nine low-trait anxiety participants completed a cue-flanker task with functional magnetic resonance imaging. The hierarchical drift diffusion model (HDDM) was used to measure the cognitive computations during the task. To identify the neurocomputational mechanism of anticipatory control in anxiety, mediation analysis and dynamic causal modelling (DCM) analysis were conducted to examine the relationship between functional connectivity of brain networks and the parameters of HDDM. RESULTS: We found influences of regulatory signals from the dorsolateral prefrontal cortex to dorsal anterior cingulate cortex on decision threshold in low-trait anxiety (LTA), but not in high-trait anxiety (HTA), especially for the condition with uncertain cues. The results indicate deficient top-down anticipatory control of upcoming conflicts in anxious individuals. DCM and HDDM analyses revealed that lower decision threshold was associated with higher intrinsic connectivity of salience network (SN) in anxious individuals, suggesting that dysfunctional SN disrupts anticipation of conflict control under uncertainty in anxiety. CONCLUSIONS: Our results suggest hyperfunction of the SN underlies the deficient information accumulation during uncertain anticipation of upcoming conflicts in anxiety. Our findings shed new light on the mechanisms of anticipation processing and the psychopathology of anxiety.

Differential effects of generalized anxiety and separation anxiety on brain structural development during adolescence.

Excessive anxiety is highly prevalent during childhood and adolescence, with detrimental effects on somatic and mental health, and quality of life. Although structural abnormalities in the brain have been found in people with anxiety disorders, whether anxiety affects the brain development of children and adolescents remains unknown. Here, we applied a multivariate approach to two single-site MRI datasets consisting of 733 and 775 participants aged 5-18 years. Using linear support vector regression and cross-validation, brain age is estimated by predicting the chronological age from the features that combine cortical thickness and surface area of 68 brain regions. We found that gray matter can predict the chronological age of children and adolescents with a low mean absolute error. Compared to specific brain network, the whole structural brain measures predicted brain age better. Importantly, adolescents with higher generalized anxiety and those with lower separation anxiety showed lower brain age, indicating a slow development of brain structures. The relationship between anxiety and brain age of youths could also be found in parent-reported separation anxiety. The findings highlight differential effects of different anxiety types on brain structural development and suggest that different types of anxiety during childhood and adolescence should be treated differently.

Photoaffinity labeling of benzophenone-containing salicylanilide compounds to give an insight into the mechanism in disrupting peptidoglycan formation.

A series of salicylanilide compounds was previously identified as antibacterial agents that inhibit the peptidoglycan formation. To find the exact binding mode, we synthesized a benzophenone-containing salicylanilide compound (1) and used it as a photoaffinity probe to label Acinetobacter baumannii penicillin-binding protein (PBP1b). After incubation and photo-irradiation, the labeled protein was subjected to trypsin digestion, dialysis enrichment, LC-ESI-MS/MS analysis, and Mascot search to reveal an octadecapeptide sequence 364RQLRTEYQESDLTNQGLR381 that was labeled at E372. Our molecular docking experiments suggest a hydrophobic pocket surrounded by R367 and E372 is the binding site of salicylanilide 1. The pocket lies in between the transglycosylase and transpeptidase domains, thus binding of salicylanilide 1 can block the propagation pathway to disrupt the growth of peptidoglycan chain.

Prescribed performance model-free adaptive sliding mode control of a shape memory alloy actuated system.

This paper concentrates on a simple and robust control method for the discrete time nonlinear systems to fulfill the requirement of predefined accuracy. A sliding mode control method is designed by introducing equivalent dynamic linearization technique according to the input/output (I/O) information merely. A square-root type error transformation method is presented for the tracking error to be restricted within a preassigned zone. The performance of presented control method is demonstrated through experiments on a nonlinear system. Experiment results show that the presented control method has a superior tracking accuracy compared with PID controller and model-free adaptive control (MFAC).

C4OH is a potential newborn screening marker-a multicenter retrospective study of patients with beta-ketothiolase deficiency in China.

BACKGROUND: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. RESULTS: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. CONCLUSION: This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study.

OBJECTIVES: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. MATERIALS AND METHODS: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). RESULTS: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. CONCLUSION: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

Genetic and Comparative Transcriptome Analysis Revealed DEGs Involved in the Purple Leaf Formation in Brassica juncea.

Brassica juncea is an important dietary vegetable cultivated and consumed in China for its edible stalks and leaves. The purple leaf mustard, which is rich in anthocyanins, is eye-catching and delivers valuable nutrition. However, the molecular mechanism involved in anthocyanin biosynthesis has not been well studied in B. juncea. Here, histological and transcriptome analyses were used to characterize the purple leaf color and gene expression profiles. Free-hand section analysis showed that the anthocyanin was mainly accumulated in the adaxial epidermal leaf cells. The anthocyanin content in the purple leaves was significantly higher than that in the green leaves. To investigate the critical genes and pathways involved in anthocyanin biosynthesis and accumulation, the transcriptome analysis was used to identify the differentially expressed genes (DEGs) between the purple and green leaves from the backcrossed BC3 segregation population in B. juncea. A total of 2,286 different expressed genes were identified between the purple and green leaves. Among them, 1,593 DEGs were up-regulated and 693 DEGs were down-regulated. There were 213 differently expressed transcription factors among them. The MYB and bHLH transcription factors, which may regulate anthocyanin biosynthesis, were up-regulated in the purple leaves. Interestingly, most of the genes involved in plant-pathogen interaction pathway were also up-regulated in the purple leaves. The late biosynthetic genes involved in anthocyanin biosynthesis were highly up-regulated in the purple leaves of B. juncea. The up regulation of BjTT8 and BjMYC2 and anthocyanin biosynthetic genes (BjC4H, BjDFR, and BjANS) may activate the purple leaf formation in B. juncea. This study may help to understand the transcriptional regulation of anthocyanin biosynthesis in B. juncea.

Controllable Drug Release Behavior of Polylactic Acid (PLA) Surgical Suture Coating with Ciprofloxacin (CPFX)-Polycaprolactone (PCL)/Polyglycolide (PGA).

Polylactic acid (PLA) surgical suture can be absorbed by human body. In order to avoid surgical site infections (SSIs), the drug is usually loaded on the PLA suture, and then the drug can release directly to the wound. Because the different types of wounds heal at different times, it is needed to control the drug release rate of PLA suture to consistent to the wound healing time. Two biopolymers, polyglycolide (PGA) and polycaprolactone (PCL), were selected as the carrier of ciprofloxacin (CPFX) drug, and then the CPFX-PCL/PGA was coated on the PLA suture. The degradation rate of drug-carrier can be controlled by adjusting the proportion of PCL/PGA, which can regulate the rate of CPFX drug release from PLA suture. The results show that the surface of PLA suture, coating with PCL/PGA, was very rough, which led to increased stitching resistance when we were suturing the wound. These materials, such as the PLA suture, the PCL/PGA carriers and the CPFX drug, were just physically mixed rather than chemically reacted, which was very useful for ensuring the original efficacy of CPFX drug. With the increasing of PCL in the carriers, both the breaking strength and elongation of these un-degraded sutures increased. During degradation, the breaking strength of all sutures gradually decreased, and the more PCL in the coating materials, the longer effective strength-time for the suture. With the increasing of PCL in the drug-carrier, the rate of drug releasing became lower. The drug release mechanism of CPFX-PCL/PGA was a synergistic effect of drug diffusion and PCL/PGA carrier dissolution.

Mannan oligosaccharide increases the growth performance, immunity and resistance capability against Vibro Parahemolyticus in juvenile abalone Haliotis discus hannai Ino.

This trial was conducted to investigate the effect of mannose oligosaccharides (MOS) on the growth performance, antioxidation, immunity and disease resistance of Vibro Parahemolyticus in juvenile abalone Haliotis discus hannai Ino. Four formulated diets were produced to contain 0.00 g/kg, 0.40 g/kg, 0.80 g/kg and 1.60 g/kg Actigen®, with functional ingredients of MOS, respectively. Accordingly, the experimental diets were named as A0, A4, A8 and A16. After 120-days feeding trial, the best growth performance was observed in A8 group (P < 0.05) and there was no significant difference in A0, A4 and A16 groups. With the increase of dietary MOS, the activity of the total antioxidant capacity in hepatopancreas is increasingly elevated (P < 0.05) while no significant difference was observed on activity of glutathione S-transferase (P > 0.05). The activities of superoxide dismutase and glutathione peroxidase were firstly increased and then decreased, with the highest values in A8 group (P < 0.05). Immune-related parameters were significantly affected by dietary MOS inclusion. Specifically, the activities of alkaline phosphatase and acid phosphatase in hepatopancreas and serum of abalone fed diets containing MOS were significantly higher than those of control A0 group (P < 0.05). Moreover, the highest values of both enzymes were observed in hepatopancreas of A8 group but in serum of A16 group, respectively. The lysozyme activities in hepatopancreas and serum of A4 group were significantly higher than those of other groups (P < 0.05) and there was no significant difference in A0, A8 and A16 groups (P > 0.05). The activities of cytophagy and respiratory burst in serum of abalone were not significantly affected by dietary MOS content (P > 0.05). The mRNA levels of focal adhesion kinase and integrin-linked kinase were gradually elevated with the increase of dietary MOS, with the highest value recorded in A16 group (P < 0.05). The gene expression of caspse-3 in A8 group was dramatically higher than those of other groups (P < 0.05) and there was no significant difference in A0, A4 and A16 groups (P > 0.05). The mRNA level of nuclear factor-κB was not significantly affected by dietary MOS (P > 0.05). During 56 h of V. Parahemolyticus challenge period, the accumulated mortality rate of abalone fed diets containing MOS were significantly lower than that of control A0 group in each time point (P < 0.05). Overall, the lowest rate was happened in A8 group (P < 0.05). In conclusion, MOS inclusion in diet has obviously positive effect on growth, immunity and disease resistance capability of abalone, with the optimal level of Actigen® at 0.80 g/kg in diet.

Degradation Behavior In Vitro of Carbon Nanotubes (CNTs)/Poly(lactic acid) (PLA) Composite Suture.

Poly(lactic acid) (PLA) suture can be absorbed by the human body, and so have wide applications in modern surgery operations. The degradation period of PLA suture is expected to meet with the healing time of different types of wounds. In order to control the degradation period of the PLA suture, the carbon nanotubes (CNTs) were composited with PLA suture, and the degradation experiment in vitro was performed on sutures. The structure and properties of sutures during degradation, such as surface morphology, breaking strength, elongation, mass and chemical structure, were tracked and analyzed. The results indicated that the degradation brought about surface defects and resulted in 13.5 weeks for the strength valid time of the original PLA suture. By contrast, the strength valid time of the CNTs/PLA suture was increased to 26.6 weeks. Whilst the toughness of both the pure PLA and CNTs/PLA sutures decreased rapidly and almost disappeared after 3 to 4 weeks of degradation. The mass loss demonstrated that the time required for complete degradation of the two sutures was obviously different, the pure PLA suture 49 weeks, while CNTs/PLA sutures 63 to 73 weeks. The research proved that CNTs delayed PLA degradation and prolonged its strength valid time in degradation.

Functional Correlates of Resting-State Connectivity in the Default Mode Network of Heroin Users on Methadone Treatment and Medication-Free Therapeutic Community Program.

The treatment of heroin addiction is a complex process involving changes in addictive behavior and brain functioning. The goal of this study was to explore the brain default mode network (DMN) functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) and decision-making performance based on the Cambridge gambling task in heroin-dependent individuals undergoing methadone treatment (MT, n = 11) and medication-free faith-based therapeutic community program (TC, n = 11). The DMN involved the medial prefrontal cortex (mPFC), left inferior parietal lobe (IPLL), right inferior parietal lobe (IPLR), and posterior cingulate cortex (PCC) subregions for all participants in both the MT and TC groups. Compared with MT, TC had an increased functional connectivity in IPLL-IPLR and IPLR-PCC and decreased functional connectivity in mPFC-IPLL and IPLL-PCC. Both groups exhibited no significant difference in the regional rs-fMRI metric [i.e., amplitude of low-frequency fluctuation (ALFF)]. In the analysis of the neural correlates for decision-making performance, risk adjustment was positively associated with ALFF in IPLL for all participants considering the group effects. The involvement of IPL in decision-making performance and treatment response among heroin-dependent patients warrants further investigation.

Thermal Failure Analysis of Fiber-Reinforced Silica Aerogels under Liquid Nitrogen Thermal Shock.

Aerogel materials are recognized as promising candidates for the thermal insulator and have achieved great successes for the aerospace applications. However, the harsh environment on the exoplanet, especially for the tremendous temperature difference, tends to affect the tenuous skeleton and performances of the aerogels. In this paper, an evaluation method was proposed to simulate the environment of exoplanet and study the influence on the fiber-reinforced silica aerogels with different supercritical point drying (SPD) technology. Thermal conductivity, mechanical property and the microstructure were characterized for understanding the thermal failure mechanism. It was found that structure and thermal property were significantly influenced by the adsorbed water in the aerogels under the thermal shocks. The thermal conductivity of CO2-SPD aerogel increased 35.5% after the first shock and kept in a high value, while that of the ethanol-SPD aerogel increased only 19.5% and kept in a relatively low value. Pore size distribution results showed that after the first shock the peak pore size of the CO2-SPD aerogel increased from 18 nm to 25 nm due to the shrinkage of the skeleton, while the peak pore size of the ethanol-SPD aerogel kept at ~9 nm probably induced by the spring-back effect. An 80 °C treatment under vacuum was demonstrated to be an effective way for retaining the good performance of ethanol-SPD aerogels under the thermal shock. The thermal conductivity increases of the ethanol-SPD aerogels after 5 shocks decreased from ~30 to ~0% via vacuum drying, while the increase of the CO2-SPD aerogels via the same treatments remains ~28%. The high-strain hardening and low-strain soften behaviors further demonstrated the skeleton shrinkage of the CO2-SPD aerogel.

Efficient preparation of crack-free, low-density and transparent polymethylsilsesquioxane aerogels via ambient pressure drying and surface modification.

Polymethylsilsesquioxane (PMSQ) aerogels have gained considerable attention due to their high transparency, good mechanical properties and low thermal conductivity. However, low-density PMSQ aerogels are difficult to obtain by ambient pressure drying due to irreversible shrinkage. Inspired by previous research, we speculate that reducing surface silanol groups could reduce irreversible shrinkage along with the skeleton-strengthening effect. In addition, extending the ageing process is expected to lead to increased density. Thus, in this paper, we applied a mature technique to modify the surfaces of PMSQ gels with terminal silane groups to reduce hydrophilic surface silanol groups without strengthening the skeletons. This surface modification process greatly reduced irreversible shrinkage and allowed the PMSQ gels to return to their original sizes, in accompany with the decrease of silanol group (NMR results as the direct evidence). This method exhibits extremely high efficiency in the preparation of crack-free, low-density and transparent PMSQ aerogels. The PMSQ aerogels dried at ambient pressure had a low density of 48 mg cm-3, low thermal conductivity (21.1 mW m-1 K-1), high transparency (81.3% at 550 nm), super-hydrophobicity (contact angle of 155°) and excellent mechanical properties. The proposed method will be useful for the industrial production of transparent insulating materials and has potential applications in space exploration.

Bronchopulmonary infection of Lophomonas blattarum: a case and literature review.

Human infections with Lophomonas blattarum are rare. However, the majority of the infections occurred in China, 94.4% (136 cases) of all cases in the world. This infection is difficult to differentiate from other pulmonary infections with similar symptoms. Here we reported a case of L. blattarum infection confirmed by bronchoalveolar lavage fluid smear on the microscopic observations. The patient was a 21-year-old female college student. The previous case which occurred in Chongqing was 20 years ago. We briefly reviewed on this infection reported in the world during the recent 20 years. The epidemiological characteristics, possible diagnostic basis, and treatment of this disease is discussed in order to provide a better understanding of recognition, diagnosis, and treatment of L. blattarum infection.

Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression.

Luteolin is a flavonoid that has been identified in many plant tissues and exhibits chemopreventive or chemosensitising properties against human breast cancer. However, the oncogenic molecules in human breast cancer cells that are inhibited by luteolin treatment have not been identified. This study found that the level of cyclin E2 (CCNE2) mRNA was higher in tumour cells (4.89-fold, (∗)P=0.005) than in normal paired tissue samples as assessed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis (n=257). Further, relatively high levels of CCNE2 protein expression were detected in tamoxifen-resistant (TAM-R) MCF-7 cells. These results showed that the level of CCNE2 protein expression was specifically inhibited in luteolin-treated (5µM) TAM-R cells, either in the presence or absence of 4-OH-TAM (100nM). Combined treatment with 4-OH-TAM and luteolin synergistically sensitised the TAM-R cells to 4-OH-TAM. The results of this study suggest that luteolin can be used as a chemosensitiser to target the expression level of CCNE2 and that it could be a novel strategy to overcome TAM resistance in breast cancer patients.

[Effects of huannao yicong recipe extract on the learning and memory and related factors of Abeta generation in the brain of APP transgenic mice].

OBJECTIVE: To study the effects of Huannao Yicong Recipe (HNYCR)extract on the learning and memory ability, and the expressions of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), presenilin-1 (PS-1), and beta amyloid protein (Abeta)in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer's disease (AD). METHODS: Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group (C57BL/6J mice), 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected: Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Abeta. RESULTS: The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal control group (P < 0.01). The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group (P < 0.05). The expressions of APP, BACE1, PS-1, and Abeta in hippocampus CA1 area of 7-month-old model mice increased significantly (P < 0.01), when compared with the normal control group. The expressions of APP, BACE1, PS-1, and Abeta in each 7-month-old intervention groups were significantly reduced, when compared with the model group (P < 0.01). CONCLUSION: Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and Abeta in the hippocampal CA1 area, reduce the production of Abeta, and slow down the pathological process of brains in APP transgenic mice.

Effect of Huannao Yicong prescription [See Text] extract on ß-amyloid precursor protein metabolic signal transduction-related protein in brain tissue of dementia model transgenic mouse.

OBJECTIVE: To observe the effect of Huannao Yicong Prescription (, HNYC, a Chinese medical compound) extract on ß-amyloid precursor protein (APP) metabolic signal transduction related protein kinase C (PKC), tyrosine amyloid protein kinase (TrKA), and glycogen synthase kinase-3 (GSK-3) in brain tissue of transgenic mouse dementia model induced by APP. METHODS: Sixty dementia model transgenic 3-month-old mice induced by APP695V717I were randomly allocated in four groups: the model group (A), the Donepezil (0.65×10(-3) g·kg(-1)·(-1))-treated group (B), and the two HNYC-treated groups (C and D) with high dosage (2.8 g·kg(-1)·(-1)) and low dosage (1.4 g·kg(-1)·(-1)) of HNYC extract, respectively, 15 mice in each group. Besides, a normal control group was set up with 15 C57BL/6J mice with the same age and genetic background as the model mice. The drugs for treatment were administered once a day by dissolving in equal-volume distilled water through gastric infusion, continued for 6 months, to mice in group A and to normal control group equal-volume distilled water was administered instead. Spatial learning and memory capacity of mice were observed by Morris water maze; their one-time escape response memory capacity was tested by diving platform; and changes of PKC, TrkA, and GSK-3 levels in hippocampus and cortex of brain were detected by Western blotting. RESULTS: HNYC extract showed significant effects on increasing the time of model mice for swimming through the flat roof and the swimming time and path in the fourth quadrant P<0.05 or P<0.01). Diving platform test showed that the latent times in Groups B and C were longer than that in Group A significantly (P <0.05 and P<0.01). Compared with the normal control group, PKC and TrkA protein expression levels in hippocampus and cortex of model mice's brain lowered significantly (P<0.01), while GSK-3 protein expression increased significantly (P<0.01); compared with Group A (the model group), hippocampal and cortical levels of PKC protein expression in the intervened groups (B-D) as well as those of TrkA in Group C were higher (P<0.01 or P<0.05), while hippocampal levels of GSK-3 in intervened groups were lower (P<0.01). CONCLUSION: HNYC extract could obviously increase the protein expressions of PKC and TrkA and decrease the expression of GSK-3 protein in brain tissue of transgenetic mice model of dementia, and regulate APP metabolic signal transduction path, and thus to suppress the production of Aß, which is one of the dominant mechanisms for improving learning/memory capacity of dementia model animals.