Effects of Unripe Black Raspberry Extract Supplementation on Male Climacteric Syndrome and Voiding Dysfunction: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Male climacteric syndrome (MCS) is a medical condition that can affect middle-aged men whose testosterone levels begin to decline considerably. These symptoms may include fatigue, decreased libido, mood swings, and disturbed sleep. MCS can be managed with lifestyle modifications and testosterone replacement. However, testosterone therapy may cause number of side effects, including an increased risk of cardiovascular issues. This study aims to evaluate the efficacy and safety of unripe black raspberry extract (BRE) against MCS and voiding dysfunction in men with andropause symptoms. A total of 30 subjects were enrolled and randomly assigned to the BRE group (n = 15) or the placebo group (n = 15). Participants were supplemented with 4800 mg BRE or placebo twice daily for 12 weeks. The impact of BRE was assessed using the Aging Male's Symptoms (AMS scale), International Prostate Symptom Score (IPSS) and the IPSS quality of life index (IPSS-QoL). Additionally, male sex hormones, lipid profiles, and anthropometric indices were assessed 6 and 12 weeks after treatment. The AMS scores did not differ significantly between the two groups. In the BRE group, the total IPSS and IPSS-QoL scores decreased significantly after 12 weeks compared to baseline (p < 0.05), but there was no significant difference compared to the placebo group. However, a significant difference was observed in the IPSS voiding symptoms sub-score compared to the placebo group. Furthermore, LDL-C and TC levels were also significantly lower in the BRE group than in the placebo group (p < 0.05). Collectively, the study provides strong evidence supporting the safety of BRE as a functional food and its supplementation potentially enhances lipid metabolism and alleviates MCS and dysuria symptoms, limiting the development of BPH.

Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers.

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed as multifunctional antiproliferative molecules against blood cancer and the associated inflammatory conditions. The targeted compounds were synthesized efficiently in three linear steps employing known chalcone starting materials. Compounds 2h, 2i, 2l, 2t, 2v and 2x having bromo or nitro substituted-phenyl rings elicited potential inhibitory effects on macrophages production of nitric oxide, PGE2 and TNF-α which are proinflammatory mediators involved in tumorigenesis and progression of blood cancer. Additionally, evaluation of direct inhibitory effects on the growth of diverse blood cancers including leukemia, lymphoma, and myeloma cell lines unveiled compound 2v as the most potential molecules eliciting at least five-folds the potency of the standard imatinib drug over the used diverse blood cancers. Furthermore, compound 2v showed good selectivity to blood cancer cells rather than normal MRC5 cells. Moreover, compound 2v triggered death of HL60 leukemia cells via apoptosis induction. In conclusion, the natural product-derived compound 2v might serve as a multifunctional lead compound for further development of agents for treatment of blood cancers.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline: 5,6,7-Trimethoxyflavan derivatives as novel potential anticancer agents modulating hippo signaling pathway.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline afforded 5,6,7-trimethoxyflavan derivatives that were efficiently synthesized in four linear steps. As lung cancer is the most lethal cancer, twenty-three synthesized compounds were evaluated against a panel of lung cancer cells. Amongst, compounds 8q and 8e showed interesting activity. Hence, compounds 8q and 8e were evaluated against panels of diverse cancers. Compounds 8q and 8e showed broad spectrum anticancer activity. However, compound 8q was more effective and, hence, was advanced for potency evaluation and characterization. Compound 8q showed comparable potencies to gefitinib, and oxaliplatin against lung and colorectal cancers, respectively, and superior potencies to temozolomide, dacarbazine, cisplatin, enzalutamide, methotrexate, imatinib against brain, skin, ovary, prostate, breast, and blood cancers, respectively. Compound 8q increased cleaved PARP, caspase 3, and 7 inducing apoptosis. In addition, it inhibited cyclins A, B1, H and cdc25c, and increased p53 triggering cell cycle arrest in G2/M phase. Moreover, it decreased YAP and increased LATS1 and p-mob1/mob1 activating hippo signaling. Furthermore, it decreased p-PI3K/PI3k, p-mTOR/mTOR and p-P70S6K/P70S6K inhibiting PI3k pathway. Together, these findings present compound 8q as a potential anticancer lead compound for further development of potential agents.

Impact of nonpharmacological interventions on cognitive impairment in women with breast cancer: A systematic review and meta-analysis.

Objective: This study aimed to examine the characteristics of research conducted on nonpharmacological interventions for cognitive impairment in patients with breast cancer and identify the primary effects of nonpharmacological interventions through a systematic review and meta-analysis. Methods: Five electronic databases were searched to identify all randomized controlled trial studies until September 30, 2022, using the key terms "breast cancer," "cognitive disorders," and their possible variations. The Cochrane Risk of Bias tool was used to assess risk of bias. The effect sizes were calculated in Hedges' g. Potential moderators influencing the intervention effects were explored. Results: Twenty-three studies were included in the systematic review, and 17 studies were included in the meta-analysis. Among the nonpharmacological interventions for patients with breast cancer, cognitive rehabilitation and physical activity were the most common, followed by cognitive behavioral therapy. The meta-analysis indicated that nonpharmacological interventions had a significant effect on attention (g â€‹= â€‹0.83; 95% CI: 0.14 to 1.52; I 2 â€‹= â€‹76%), immediate recall (g â€‹= â€‹0.33; 95% CI: 0.18 to 0.49; I 2 â€‹= â€‹0%), executive function (g â€‹= â€‹0.25; 95% CI: 0.13 to 0.37; I 2 â€‹= â€‹0%), and processing speed (g â€‹= â€‹0.44; 95% CI: 0.14 to 0.73; I 2 â€‹= â€‹51%) among objective cognitive functions, as well as subjective cognitive function (g â€‹= â€‹0.68; 95% CI: 0.40 to 0.96; I 2 â€‹= â€‹78%). Intervention type and mode of delivery were potential moderators for the effects of nonpharmacological interventions on cognitive functions. Conclusions: Nonpharmacological interventions can improve subjective and objective cognitive functioning among patients with breast cancer undergoing cancer treatment. Therefore, it is necessary to provide nonpharmacological interventions by screening patients at high risk of cancer-related cognitive impairment. Systematic review registration: CRD42021251709.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human.

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

Lemon balm and dandelion leaf extract synergistically alleviate ethanol-induced hepatotoxicity by enhancing antioxidant and anti-inflammatory activity.

We investigated the effect of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (LD) on ethanol (EtOH)-mediated liver injury and explored the underlying mechanisms. Administration of LD synergistically reduced relative liver weight and decreased the levels of serum biomarkers of hepatic injury. Histopathological and biochemical analyses indicated that LD synergistically attenuated hepatic accumulation of triacylglycerides (TGs) and restored the levels of mRNAs related to fatty acid metabolism. In addition, LD significantly reduced EtOH-induced hepatic oxidative stress by attenuating the reduction in levels of nuclear factor E2-related factor 2 (Nrf2) mRNA and enhancing antioxidant activity. Moreover, LD decreased the EtOH-mediated increase in levels of hepatic tumor necrosis factor-α (TNF-α) mRNA. In vitro, LD significantly scavenged free radicals, increased cell viability against tert-butylhydroperoxide (tBHP), and transactivated Nrf2 target genes in HepG2 cells. Furthermore, LD decreased levels of pro-inflammatory mediators in lipopolysaccharide-stimulated Raw264.7 cells. Therefore, LD shows promise for preventing EtOH-mediated liver injury. PRACTICAL APPLICATIONS: There were no approved therapeutic agents for preventing and/or treating alcoholic liver diseases. In this study, a 2:1 (w/w) mixture of lemon balm and dandelion leaf extract (DL) synergistically ameliorated EtOH-induced hepatic injury by inhibiting lipid accumulation, oxidative stress, and inflammation. Our findings will enable the development of a novel food supplement for the prevention or treatment of alcohol-mediated liver injury.

In-vivo half-life and hypoglycemic bioactivity of a fusion protein of exenatide and elastin-based polypeptide from recombinant Saccharomyces cerevisiae.

Exenatide (Ex) is a 39-amino acid peptide of glucagon-like peptide-1 (GLP-1) receptor agonist that was approved by the FDA in 2005 as a Type II diabetes treatment. It shows a 53% homology with GLP-1 but has an extended half-life (ca. 2.4 h) relative to GLP-1 (ca. 2-3 min). In this study, to further extend its in vivo half-life, we constructed a fusion protein (Ex-(EBP)10-6xHis) using a biocompatible and inert elastin-based polypeptide (EBP) as a fusion partner. Valine was inserted into the guest position of the pentapeptide (VPGXG), no linker sequence was inserted in between the EBPs, and (EBP)10-6xHis tag was attached to the C-terminus of exenatide. By using a recombinant Saccharomyces cerevisiae expression system, the fusion protein was expressed and secreted to the broth and purified by Ni-NTA affinity chromatography. Compared with the native exenatide, the physical half-life of the fusion protein was ca. 3.7-fold extended while approximately 72% of the in-vitro insulin secreting activity was maintained. However, the biological half-life measured by a glucose tolerance test (GTT) and the hypoglycemic test in mice was not significantly different from that of the native form. The effects of EBPylation on bioactivity and half-life of the fusion protein are similar to those of PEGylation. The result suggests that the bioactivity and half-life should be carefully balanced to obtain optimal fusion proteins. We expect that EBPylation using an optimal repeat number of EBP can be an alternative to chemical modification for therapeutic biobetters with extended half-life.

Erythroid differentiation regulator 1 strengthens TCR signaling in thymocytes by modulating calcium flux.

Erythroid differentiation regulator 1 (Erdr1) has been identified as a stromal survival factor released under stressful conditions. Previously, Erdr1 was reported to be expressed highly in thymus, but roles of Erdr1 in thymus were not known. Here, the effects of Erdr1 on T cell development were investigated. The expression of Erdr1 was higher in thymus than bone marrow and Erdr1 was detected in both the cortex and medulla of thymus. Erdr1 treatment significantly induced the expression of activation marker, CD69, from thymocytes in the presence of TCR stimuli in vitro and the induction was dependent on increased Ca2+ influx. In addition, in vivo administration of Erdr1 resulted in significant increase of total and positive selected thymocyte numbers, particularly in the number of CD3TCRhiCD69+ DP thymocytes. Taken together, our results show that Erdr1 enhances the strength of TCR signaling and cellularity of thymocytes by amplifying Ca2+ influx in thymocytes receiving TCR signals.

Gypenoside UL4-Rich Gynostemma pentaphyllum Extract Exerts a Hepatoprotective Effect on Diet-Induced Nonalcoholic Fatty Liver Disease.

Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.

ERK activating peptide, AES16-2M promotes wound healing through accelerating migration of keratinocytes.

Wound healing is an important issue that influences quality of life, and the need for products associated with wound healing is growing annually. New materials and therapies for skin wounds are being continuously researched and developed in order to increase treatment efficacy. Here, we show that the peptide AES16-2M comprised of five short amino acid sequences (REGRT) demonstrates efficacy in wound healing. AES16-2M exerted more effective healing than the control in an acute wound model, and tissue regeneration was similar to that of normal tissue in AES16-2M-treated skin. We found that the increase in re-epithelialization by AES16-2M early in wound development was due to migration of keratinocytes; a scratch assay using a human keratinocyte cell line (HaCaT) also demonstrated effective wound closure by AES16-2M. The migration of keratinocytes effected by AES16-2M was promoted through ERK phosphorylation and blocked with U0126, an ERK inhibitor. Moreover, AES16-2M treatment stimulated human dermal fibroblast (HDF) migration as well as keratinocyte. Taken together, these results suggest that AES16-2M can be an effective therapeutic agent for wound healing by promoting migration of keratinocytes and fibroblasts via ERK phosphorylation.

Mulberry leaf extract displays antidiabetic activity in db/db mice via Akt and AMP-activated protein kinase phosphorylation.

BACKGROUND: Augmenting glucose utilization in skeletal muscle via the phosphatidylinositol-3 kinase (PI3 kinase)/protein kinase B (Akt) pathway or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway is necessary to regulate hyperglycemia in patients with type 2 diabetes mellitus. OBJECTIVE: We investigated the effect of mulberry leaf extract (MLE) on glucose uptake in skeletal muscle cells and explored its in vivo antidiabetic potential. DESIGN: Male db/db mice were treated with either MLE (50 mg/kg, 100 mg/kg, and 250 mg/kg) or metformin (100 mg/kg) for 8 weeks. RESULTS: MLE treatment stimulated glucose uptake, driven by enhanced translocation of glucose transporter 4 to cell membranes in L6 myotubes. These effects of MLE were synergistic with those of insulin and were abolished in the presence of PI3K inhibitor or AMPK inhibitor. In db/db mice, supplementation with MLE decreased fasting blood glucose and insulin levels and enhanced insulin sensitivity, with increases of p-Akt and p-AMPK in skeletal muscle. Moreover, MLE improved blood lipid parameters and attenuated hepatic steatosis in diabetic db/db mice. DISCUSSION: These findings suggest that MLE exerts antidiabetic activity through stimulating glucose disposal in skeletal muscle cells via the PI3K/Akt and AMPK pathways. CONCLUSIONS: MLE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway.

The prevalence of metabolic diseases has risen globally in parallel with the obesity epidemic over the past few decades. Green tea has been reported to have metabolically beneficial effects on obesity; however, the mechanism by which green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12 weeks. GTE supplementation reduced body weight gain, prevented hepatic fat accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and insulin resistance in HFD-fed mice. The underlying mechanisms of these beneficial effects of GTE might involve the upregulation of sirtuin 1 and AMP activated protein kinase (AMPK) and the downregulation of enzymes related to de novo lipogenesis. Consistent with the in vivo findings, GTE increased the expression and activity of sirtuin 1, enhanced the binding of sirtuin 1 to liver kinase B1 (LKB1) and subsequent deacetylation of LKB1, and reduced triglyceride accumulation in HepG2 cells. These results suggest the possible therapeutic potential of dietary epigallocatechin gallate-rich GTE supplementation for preventing the development and progression of hepatic steatosis and obesity.

Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells.

Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06µM) and MCF-7 (GI50=7.67µM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile.

Functional Properties of Microorganisms in Fermented Foods.

Fermented foods have unique functional properties imparting some health benefits to consumers due to presence of functional microorganisms, which possess probiotics properties, antimicrobial, antioxidant, peptide production, etc. Health benefits of some global fermented foods are synthesis of nutrients, prevention of cardiovascular disease, prevention of cancer, gastrointestinal disorders, allergic reactions, diabetes, among others. The present paper is aimed to review the information on some functional properties of the microorganisms associated with fermented foods and beverages, and their health-promoting benefits to consumers.

The Antioxidant Properties and Inhibitory Effects on HepG2 Cells of Chicory Cultivated Using Three Different Kinds of Fertilizers in the Absence and Presence of Pesticides.

The objective of this study was to explore the antioxidant levels and anticancer properties of chicory cultivated using three different kinds of fertilizers (i.e., developed, organic, and chemical) in the presence and absence of pesticides. Phenolic phytochemicals, including total polyphenols and flavonoids, and antioxidant activities, including reducing power, ABTS+ and DPPH radical scavenging activity, were analyzed using several antioxidant assays. HepG2 cell viability was analyzed using the MTT assay. The antioxidant properties of chicory were found to increase when cultivated with chemical fertilizer in the absence of pesticides. On the other hand, antioxidant capacity was higher in chicory cultivated with eco-developed fertilizer even in the presence of pesticides. Chicory grown using eco-developed or organic fertilizer was more effective in suppressing the proliferation of HepG2 cells when compared to chicory grown with chemical fertilizer. This effect was time dependent, regardless of treatment with or without pesticides. In conclusion, the antioxidant activity of chicory were affected by the presence or absence of pesticides. However, developed and organic fertilizers showed a strong anti-proliferative effect against HepG2 cells, regardless of the presence or absence of pesticides.

Incidental Breast Lesions Identified by (18)F-FDG PET/CT: Which Clinical Variables Differentiate between Benign and Malignant Breast Lesions?

PURPOSE: The aim of our study was to evaluate the risk of malignancy and to determine which clinical variables differentiate between benign and malignant focal breast lesions found incidentally on (18)F-flourodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT). METHODS: From March 2005 to October 2011, 21,224 women with no history of breast cancer underwent FDG PET/CT at three university-affiliated hospitals. We retrospectively identified 214 patients with incidental focal hypermetabolic breast lesions and grouped them into benign and malignant lesion groups. Of the 214 patients, 82 patients with 91 lesions were included in this study. All lesions were confirmed histologically or were assessed by follow-up imaging for greater than 2 years. The patient age, maximum standardized uptake value (SUVmax), lesion size on ultrasonography (US), and Breast Imaging-Reporting and Data System (BI-RADS) category on US in conjunction with mammography were compared between the groups. Multivariate logistic regression analysis was used to identify independent factors associated with malignancy. RESULTS: The risk of malignancy was 29.7% (27/91) in breast incidentalomas detected by FDG PET/CT. The univariate analysis showed that the patient age, SUVmax, tumor size, and BI-RADS category differed significantly between the malignant and benign groups. The multivariate analysis showed that the BI-RADS category was the only significant factor differentiating benign from malignant lesions (p=0.002). CONCLUSION: BIRADS category based on US in conjunction with mammography was the only useful tool to differentiate between malignant and benign lesions in breast incidentalomas on FDG PET/CT.

Quantitative anatomical analysis of facial expression using a 3D motion capture system: Application to cosmetic surgery and facial recognition technology.

The topography of the facial muscles differs between males and females and among individuals of the same gender. To explain the unique expressions that people can make, it is important to define the shapes of the muscle, their associations with the skin, and their relative functions. Three-dimensional (3D) motion-capture analysis, often used to study facial expression, was used in this study to identify characteristic skin movements in males and females when they made six representative basic expressions. The movements of 44 reflective markers (RMs) positioned on anatomical landmarks were measured. Their mean displacement was large in males [ranging from 14.31 mm (fear) to 41.15 mm (anger)], and 3.35-4.76 mm smaller in females [ranging from 9.55 mm (fear) to 37.80 mm (anger)]. The percentages of RMs involved in the ten highest mean maximum displacement values in making at least one expression were 47.6% in males and 61.9% in females. The movements of the RMs were larger in males than females but were more limited. Expanding our understanding of facial expression requires morphological studies of facial muscles and studies of related complex functionality. Conducting these together with quantitative analyses, as in the present study, will yield data valuable for medicine, dentistry, and engineering, for example, for surgical operations on facial regions, software for predicting changes in facial features and expressions after corrective surgery, and the development of face-mimicking robots.

Ectopic overexpression of castor bean LEAFY COTYLEDON2 (LEC2) in Arabidopsis triggers the expression of genes that encode regulators of seed maturation and oil body proteins in vegetative tissues.

The LEAFY COTYLEDON2 (LEC2) gene plays critically important regulatory roles during both early and late embryonic development. Here, we report the identification of the LEC2 gene from the castor bean plant (Ricinus communis), and characterize the effects of its overexpression on gene regulation and lipid metabolism in transgenic Arabidopsis plants. LEC2 exists as a single-copy gene in castor bean, is expressed predominantly in embryos, and encodes a protein with a conserved B3 domain, but different N- and C-terminal domains to those found in LEC2 from Arabidopsis. Ectopic overexpression of LEC2 from castor bean under the control of the cauliflower mosaic virus (CaMV) 35S promoter in Arabidopsis plants induces the accumulation of transcripts that encodes five major transcription factors (the LEAFY COTYLEDON1 (LEC1), LEAFY COTYLEDON1-LIKE (L1L), FUSCA3 (FUS3), and ABSCISIC ACID INSENSITIVE 3 (ABI3) transcripts for seed maturation, and WRINKELED1 (WRI1) transcripts for fatty acid biosynthesis), as well as OLEOSIN transcripts for the formation of oil bodies in vegetative tissues. Transgenic Arabidopsis plants that express the LEC2 gene from castor bean show a range of dose-dependent morphological phenotypes and effects on the expression of LEC2-regulated genes during seedling establishment and vegetative growth. Expression of castor bean LEC2 in Arabidopsis increased the expression of fatty acid elongase 1 (FAE1) and induced the accumulation of triacylglycerols, especially those containing the seed-specific fatty acid, eicosenoic acid (20:1(Δ11)), in vegetative tissues.

Design, synthesis, screening, and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors.

A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC50 value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed.