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Background: Advance care planning (ACP) is an integral part of good quality end-of-life care. This study aimed to explore the role and practice of ACP among health and social care professionals (HSCPs) in a community long-term care facility., Methods: This was a mixed-methods study. The study purposefully sampled 12 HSCPs from one community long-term care facility in Macao, China. All data were collected in November 2022., Results: Some participants had discussed with terminally ill residents or with families in terms of end-of-life care preferences, the average correct rate of ACP knowledge was 67.4%. Interview data showed that HSCPs were primarily concerned with information-giving. The responsibility of decision-making was found to have been placed predominantly on family members of the residents., Conclusion: Study findings raised awareness in that the execution of ACP has remained in discord with the expectations in practicing ACP. The study illuminated that the perceived sense of responsibility among HSCPs was influenced by the potential legal risks involved and consequentially impacted on the adherence to individual's decisions.

Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C -terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C -terminal hydroxamate-derived [ 68 Ga]Ga-LW02075 ([ 68 Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [ 68 Ga]Ga-LW02050 ([ 68 Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [ 68 Ga]Ga-SB3 ([ 68 Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (K i ) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [ 68 Ga]Ga-SB3 and [ 68 Ga]Ga-LW02050 in PET images, but not by [ 68 Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [ 68 Ga]Ga-LW02050 was comparable to that of [ 68 Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [ 68 Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [ 68 Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [ 68 Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [ 68 Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [ 68 Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.

Fibroblast activation protein-α (FAP) is a marker of cancer-associated fibroblasts (CAFs) that constitute a significant portion of most carcinomas. Since it plays a critical role in tumor growth and metastasis, its timely detection to identify tumor lesions in early developmental stages using targeted radiopharmaceuticals has gained significant impetus. In the present work, two novel FAP-targeted precursors SB03178 and SB04033 comprising of an atypical benzo[h]quinoline construct were synthesized and either chelated to diagnostic radionuclide gallium-68 or therapeutic radionuclide lutetium-177, with ≥90% radiochemical purities and 22-76% decay-corrected radiochemical yields. nat Ga-labeled complexes displayed dose-dependent FAP inhibition, with binding potency of nat Ga-SB03178 being ∼17 times higher than nat Ga-SB04033. To evaluate their pharmacokinetic profiles, PET imaging and ex vivo biodistribution analyses were executed in FAP-overexpressing HEK293T:hFAP tumor-bearing mice. While both tracers displayed clear tumor visualization that was primarily FAP-arbitrated, with negligible uptake in most peripheral tissues, [ 68 Ga]Ga-SB03178 demonstrated higher tumor uptake and superior tumor-to-background contrast ratios than [ 68 Ga]Ga-SB04033. 177 Lu-labeled SB03178 was subjected to tumor retention studies, mouse dosimetry profiling and mouse-to-human dose extrapolations also using the HEK293T:hFAP tumor model. [ 177 Lu]Lu-SB03178 exhibited a combination of high and sustained tumor uptake, with excellent tumor-to-critical organ uptake ratios resulting in a high radiation absorbed dose to the tumor and a low estimated whole-body dose to humans. Our preliminary findings are considerably encouraging to support clinical development of [ 68 Ga]Ga-/[ 177 Lu]Lu-SB03178 theranostic pair for use in a vast majority of FAP-overexpressing neoplasms, particularly carcinomas., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuo-Shyan Lin reports a relationship with Alpha-9 Oncology Inc that includes: consulting or advisory, equity or stocks, and funding grants. Helen Merkens reports a relationship with Alpha-9 Oncology Inc that includes: equity or stocks. Francois Benard reports a relationship with Alpha-9 Oncology Inc that includes: board membership, consulting or advisory, equity or stocks, and funding grants. Hsiou-Ting Kuo reports a relationship with Alpha-9 Oncology Inc that includes: employment and equity or stocks. Zhengxing Zhang reports a relationship with Alpha-9 Oncology Inc that includes: equity or stocks. Kuo-Shyan Lin has patent #PCT/CA2023/050040 pending to Provincial Health Services Authority. Francois Benard has patent #PCT/CA2023/050040 pending to Provincial Health Services Authority. Zhengxing Zhang has patent #PCT/CA2023/050040 pending to Provincial Health Services Authority. Shreya Bendre has patent #PCT/CA2023/050040 pending to Provincial Health Services Authority. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Advance care planning (ACP) is a crucial process in clinical practice, enabling individuals to articulate their care preferences and goals, with significant implications for future healthcare. However, ACP practice of health and social care professionals (HSCPs) concerning patients, or their family members are rarely explored. The objective of the study was to adapt and validate a four-item scale assessing ACP practices of HSCPs toward patients or their family members. The ACP Practice Scale was evaluated through a cross-sectional online survey administered to HSCPs in Macao, assessing its factor structure, validity, and reliability. Based on a sample of 186 valid responses, the ACP Practice Scale demonstrated satisfactory levels of validity and reliability among HSPCs in Macao. The four-item scale explained 65.87% of the variance in ACP practice and exhibited strong internal consistency, with Cronbach's alpha and McDonald's omega coefficients of 0.82. Furthermore, item factor loadings ranged from 0.71 to 0.90. The ACP Practice Scale provides reliable and valid measurements of ACP practice among HSCPs. This instrument can help to enhance our understanding of ACP practices in clinical settings and support the advancement of advance care planning.

Companies are increasingly asking their employees to find creative solutions to their problems. However, the office environment may reduce an employee's creative potential. In this study, the role of indoor air quality parameters (PM 2.5 , TVOC, and CO 2 ) in maintaining a creative environment (involving lateral thinking ability) was evaluated by Serious Brick Play (SBP), an adaptation of the LEGO Serious Play (LSP) framework. This study was conducted in a simulated office space with 92 participants over a period of 6 weeks. The SBP required participants to address a challenge by building using Lego bricks, and then describe the solution within a given timeframe. The creations and descriptions were then graded in terms of originality, fluency, and build. The results indicated that higher TVOC levels were significantly associated with lower-rated creative solutions. A 71.9% reduction in TVOC (from 1000 ppb), improves an individual's full creative potential by 11.5%. Thus, maintaining a low TVOC level will critically enhance creativity in offices., (© 2023. Springer Nature Limited.)

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between necroptosis and apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering necroptosis/apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

Aims: Generalized trust is a crucial determinant of individual and social well-being and is the fundamental element of a healthy society. However, a decline in generalized trust was observed among Hong Kong young adults, despite local neighborhoods, and placed-based experiences gaining popularity among Hong Kong young people. Hence, this paper examines the effect of neighborhood-level factors on promoting generalized trust., Method: Cross-sectional data were obtained from 1635 young adults aged 17-23 through mixed-mode surveys-a computer-assisted telephone interviewing CATI telephone survey, an online survey, and a mail survey., Results: Logistic regression results showed that neighborhood cohesiveness, being an active member of a religious organization, being an active member of a local youth organization, acceptance of ethnic diversity, and having a good parental relationship were related to higher odds of reporting generalized trust., Conclusion: Research and practice implications and the international relevance of the findings are discussed., (© 2021 Wiley Periodicals LLC.)

Purpose: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making., Methods: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010-2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination., Results: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound ( p = 0.018) or mammography ( p = 0.026), microcalcifications ( p = 0.047), diffuse microcalcification distribution ( p = 0.034), mammographic parenchymal density ( p = 0.008). and ≥ 3 separate ADH foci found on biopsy ( p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005-0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21-25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831-1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram., Conclusion: Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74-0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH., Competing Interests: The authors declare that they have no competing interests., (© 2022 Korean Breast Cancer Society.)

Background: Celiac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines published in 2012 suggested a no-biopsy pathway (NBP) for symptomatic children with IgA tissue transglutaminase (TGA-IgA) ≥10x upper limit of normal (ULN). Biopsy confirmation remained mandatory for other cases., Objective: This retrospective case note study was aimed at evaluating the adherence to the ESPGHAN 2012 guidelines for diagnosing CD in our unit., Methods: Forty-three cases with positive TGA-IgA were identified by a laboratory database search from January 2013 to December 2019. 6 of 43 patients were not referred for a confirmation of CD diagnosis. Data was collected on the diagnostic pathways followed, and appropriateness of adherence was compared with the existing ESPGHAN guidelines., Results: A total of 37 cases were included with 35 children diagnosed with CD. 29/35 (83%) were diagnosed via the NBP;15/29 (52%) children did not meet all the criteria required for NBP, but were diagnosed and managed as having CD. 20/35 (57%) children were diagnosed with CD in adherence to the 2012 guidelines., Conclusion: The recommended diagnostic guidelines were frequently not implemented; adherence to the guidelines may improve following regular educational sessions. The revised 2020 ESPGHAN guidelines which exclude HLA-DQ2/DQ8 testing would address the issue of diagnosis for the 10/15 NBP cases (with TGA-IgA >10xULN) in our study who did not have HLA testing and were therefore non-adherent to the 2012 diagnostic guidelines. NBP, with the reduced need for endoscopy may be beneficial in resource limited settings.

Our behaviors are regulated by our perception of the future based on past experiences and knowledge. Children from a disadvantaged background might encounter obstacles more frequently when they plan their future. It is possible that a good relationship with an adult volunteer who provides assistance and guidance in the disadvantaged youth's development may facilitate their future-planning style and career goal setting. The present study investigated the role of a good mentoring relationship in promoting a disadvantaged youth's future-planning style and goal-setting ability. It focused on children from a disadvantaged background who participated in the Child Development Fund (CDF) in Hong Kong. In the study, 187 CDF participants (93 with high mentoring-relationship quality [MRQ] and 94 with low MRQ) and 208 comparison group participants were able to complete all four times of the survey. Repeated-measures analyses of covariance showed that Group main effects were observed for both future-planning style, F(2, 374) = 5.92, p < .01, and career goal-setting self-efficacy, F(2, 376) = 6.07, p < .01. Main Time effect was also found for the latter, F(3, 1128) = 7.99, p < .01. A significant Group × Time interaction effect was observed for future-planning style only, F(5.78, 1081.21) = 2.17, p < .05. Our results suggest that participants with high MRQ outperformed the comparison group in both future-planning style and career goal-setting self-efficacy. Multiple regression analyses revealed that mean MRQ score accounted for 3.9% (p < .01) of the variance in future-planning style and 4.1% (p < .01) of the variance in career goal-setting self-efficacy, supporting the role of a good mentoring relationship. Mentors have introduced new resources to the disadvantaged youths with high MRQ and have promoted the development of various skills through modeling., (© 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background & Aims: Patients undergoing gastrointestinal operations are at risk of malnutrition which may increase the chance of adverse surgical outcomes. This prospective study aimed at correlating nutritional status of patients having gastrointestinal operations with their short-term surgical outcomes captured by a territory-wide Surgical Outcomes Monitoring and Improvement Program., Methods: The preoperative malnutrition risk of Chinese adult patients undergoing elective/emergency ultra-major/major gastrointestinal operations in two surgical departments over a 12-month period were assessed by Chinese version of Malnutrition Universal Screening Tool. Their perioperative risk factors and clinical outcomes, including length of hospital stay, mortality and morbidity, were retrieved from the above mentioned program. Correlation of malnutrition risk with clinical outcomes was assessed by logistic regression analysis after controlling for known confounders., Results: 943 patients (58% male; mean age 65.9 ± 14.8 years) underwent gastrointestinal operations (40.3% emergency operation; 52.7% ultra-major procedures; 66.9% bowel resections) had analyzable data. 15.8% and 17.1% of patients were at medium and high risk of malnutrition, respectively. Malnutrition risk score according to the screening tool was an independent predictor of length of hospital stay, 30-day mortality, 60-day mortality and minor medical complications. Similar correlations were found for various sub-scores of malnutrition risk. Weight loss sub-score was predictive of 30-day mortality, 60-day mortality and minor medical complications. Body mass index was predictive of mortality (30- and 60- day) whereas the acute disease sub-score was predictive of length of hospital stay., Conclusions: Preoperative malnutrition was an important predictor of poor clinical outcomes in patients undergoing gastrointestinal operations in Hong Kong., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The reliable and accurate identification of cancer categories is crucial to a successful diagnosis and a proper treatment of the disease. In most existing work, samples of gene expression data are treated as one-dimensional signals, and are analyzed by means of some statistical signal processing techniques or intelligent computation algorithms. In this paper, from an image-processing viewpoint, a spectral-feature-based Tikhonov-regularized least-squares (TLS) ensemble algorithm is proposed for cancer classification using gene expression data. In the TLS model, a test sample is represented as a linear combination of the atoms of a dictionary. Two types of dictionaries, namely singular value decomposition (SVD)-based eigenassays and independent component analysis (ICA)-based eigenassays, are proposed for the TLS model, and both are extracted via a two-stage approach. The proposed algorithm is inspired by our finding that, among these eigenassays, the categories of some of the testing samples can be assigned correctly by using the TLS models formed from some of the spectral features, but not for those formed from the original samples only. In order to retain the positive characteristics of these spectral features in making correct category assignments, a strategy of classifier committee learning (CCL) is designed to combine the results obtained from the different spectral features. Experimental results on standard databases demonstrate the feasibility and effectiveness of the proposed method.

The putative tumor suppressor Mst1, when cleaved to its 36kDa cleaved form, amplifies apoptotic signals. We found that Mst1 was predominantly expressed in its full-length form in 76% (17/25 cases) of hepatocellular carcinoma (HCC) tumors. Mst1 cleavage was basically absent in HCC cells. Ectopic full-length Mst1 expression increased the growth of HCC cells by 55-80% within 3days after transfection. Expression of exogenous NORE1B, a tumor suppressor commonly lost in HCC tumors (~56% of our cohort), was sufficient to suppress the growth promotion of full-length Mst1. Hence, Mst1 exhibits a growth promoting activity in HCC cells upon NORE1B downregulation., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables that exhibits antitumor activity. In this study, AITC was shown to inhibit the proliferation of human metastatic colorectal adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the G2/M phase. The signaling pathway of AITC action involved the down-regulation of the pivotal Cdc25B and Cdc25C protein phosphatases in the treated cells. Quantitative real-time PCR of AITC-treated SW620 cells revealed a time-dependent down-regulation of Cdc25B and Cdc25C mRNA levels, which resulted in a decrease in the expression levels of these two proteins. Upon prolonged exposure, AITC induced caspase-mediated apoptosis in SW620 cells. The apoptotic process was evidenced by the activation of initiator caspases (-8 and -9) and effector caspases (-3 and -7), and the cleavage of poly(ADP-ribose) polymerase (PARP). The antitumor activity of AITC was further demonstrated in a SW620 xenograft in vivo. Taken together, the results suggest that AITC is a potential candidate for future research in chemoprevention and chemotherapy.

The effects of folic acid (5.7 and 71 microg/kg, 4 weeks) consumption on the beta-adrenoceptors (beta-ARs)-elicited lipolysis in vitro of the abdominal adipocytes of lean/control (+m/+db) and obese/diabetic (+db/+db) mice (female) were investigated. beta-AR agonists (salbutamol, a beta(2)-AR agonist; BRL 37344 and CGP 12177, beta(3)-AR agonists; adrenaline, a beta-AR agonist)-mediated lipolysis, beta(2)-, and beta(3)-ARs protein expression of the adipose tissues after folic acid consumption were evaluated. Our results demonstrate that a smaller magnitude of the basal (spontaneous) and the beta-AR agonists-triggered lipolysis was observed in +db/+db mice, and folic acid supplementation (71 microg/kg) resulted in an improvement of both the baseline and the beta-ARs-mediated lipolysis. In controls, a lower beta(2)-and beta(3)-ARs protein expression of the adipose tissues was detected in +db/+db mice, compared to +m/+db mice. In both strains fed with folic acid (71 microg/kg), a reduction of beta(2)-AR protein expression was observed compared to the respective controls. In +db/+db mice, folic acid (5.7 and 71 microg/kg) consumption caused a dose-dependent increase of beta(3)-AR protein expression compared to controls. We demonstrate that lipolysis elicited by beta-AR (beta(2)- and beta(3)-ARs) agonists was blunted in +db/+db mice. Folic acid consumption has significant modulatory effects on beta-ARs protein expression and lipolysis.

Background and Purpose: The present study was designed to determine how ginsenoside Rg1, an active ingredient in ginseng root, exerts its oestrogenic effects. We hypothesize that Rg1 may exert oestrogen-like actions in MCF-7 cells by activating the mitogen-activated protein kinase (MAPK) pathway in a ligand-independent manner., Experimental Approach: MCF-7 cells were co-incubated with the MAPK inhibitor PD98059 to determine whether the stimulant effects of Rg1 on cell proliferation, the induction of IGF-IR and pS2, the functional transactivation of oestrogen receptor-alpha (ERalpha), as well as ERalpha phosphorylation are dependent on MAPK. The time-dependent responses of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated protein kinase (ERK) to Rg1 in MCF-7 cells were studied. The responses of MEK phosphorylation to Rg1 in oestrogen receptor (ER)-negative HEK293 cells were also determined. The effects of Rg1 on cell proliferation and IGF-IR protein expression were studied in the presence of tyrosine kinase inhibitor genistein to elucidate the involvement of tyrosine kinase in mediating these effects., Key Results: The oestrogenic effects of Rg1 in MCF-7 cells were abolished in the presence of PD98059. Rg1 could induce MEK protein expression and the phosphorylation level of MEK and ERK significantly in a time- and dose-dependent manner. Rg1 activated MEK phosphorylation in ER-negative HEK293 cells in a time- and dose-dependent manner. Rg1 induction of cell proliferation and IGF-IR protein expression was abolished by co-treatment with genistein., Conclusions and Implications: Taken together, these results show that the MAPK pathway is involved in mediating the oestrogen-like actions of Rg1 in MCF-7 cells and suggest that Rg1 may activate ERalpha via MEK/ERK in a ligand-independent manner.

We investigated the role(s) of monoamine oxidases (MAOs) on the altered 5-hydroxytryptamine (5-HT, serotonin)-induced tension development of the isolated umbilical artery of preeclamptic pregnancy of Chinese women. An enhanced 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy was observed when compared with that of normal pregnancy. The enhanced component of 5-HT-induced tension development was eradicated by clorgyline (a MAO-A inhibitor). Blockade of eNOS (endothelial isoform nitric oxide synthase) (N(omega)-nitro-L-arginine methyl ester), 5-HT transporter (citalopram), 5-HT receptor subtypes (5HT2B, SB 204741; 5-HT2C, RS 102221; 5-HT7, SB 269970), and endothelium denudation of the umbilical artery of normal pregnancy mimicked the enhanced 5-HT-induced tension development as observed in the preeclamptic tissues. In contrast, no apparent changes in 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy were observed with the same pharmacological manipulations. A decreased protein expression levels of MAO-A and eNOS (no iNOS and MAO-B expression was detected) and no change in caveolin-1 and 5-HT transporter expression were demonstrated in the umbilical artery (endothelium intact) lysate of preeclamptic pregnancy, compared to that of the umbilical artery of normal pregnancy. Thus, in the umbilical artery of preeclamptic pregnancy, a decrease of MAO-A and eNOS protein expression levels are probably associated with, or responsible for, the exaggerated 5-HT-induced tension development.

Ginsenoside Rg1, an active ingredient commonly found in ginseng root, was previously demonstrated to be a phytoestrogen that exerted estrogen-like activity without direct interaction with estrogen receptors (ERs) in human breast cancer (MCF-7) cells. The present study was designed to determine the molecular mechanism by which Rg1 exerted estrogenic effects. Co-incubation of MCF-7 cells with 1 microM of ER antagonist ICI182780 abolished the inductive effects of Rg1 on pS2 expression as well as ERE-luciferase activity, suggesting that the estrogenic effects of Rg1 were mediated through the endogenous ERs. To evaluate the relative involvement of ERalpha and ERbeta in mediating the actions of Rg1, ER-negative human embryonic kidney (HEK293) cells were co-transfected with the ERE-luciferase reporter construct and either ERalpha or ERbeta construct. The results showed that Rg1 could activate ERE-luciferase activity via the ERalpha-mediated pathway in a dose-dependent manner (10(-14) to 10(-6)M); whereas, the activation of ERbeta-mediated ERE-luciferase activity by Rg1 only occur at high concentration (10(-6)M). Furthermore, the results showed that 1pM Rg1 could rapidly induce phosphorylation of the AF-1 domain of ERalpha at serine 118 residue within the first 5 min of incubation, suggesting that Rg1 activates ERalpha in a ligand-independent manner. Taken together, our results indicate that Rg1 preferentially activates ERalpha via phosphorylation of AF-1 domain in the absence of receptor binding. This study is the first to provide evidence that ginsenoside Rg1 exerts estrogen-like actions via ligand-independent activation of ERalpha pathway.

Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen-responsive pS2 mRNA expression (P<0.05) without alteration of estrogen receptor alpha (ERalpha) protein or mRNA expression in MCF-7 cells. In addition, 10(-14)-10(-4) M of Rg1 does not demonstrate specific binding to ERalpha. We hypothesize that Rg1 may exert its actions in MCF-7 cell via the activation of crosstalk between ER- and insulin growth factor I receptor (IGF-IR)-dependent pathways. The results indicate that Rg1 significantly increases IGF-IR expression and IGF-IR promoter activity in MCF-7 cells (P<0.05). Cotreatment of MCF-7 cells with 1 muM of estrogen antagonist ICI 182,780 completely abolishes the effects of Rg1 on IGF-IR expression.Furthermore, Rg1 enhances tyrosine phosphorylation of IRS-1 in MCF-7 cells upon IGF-I stimulation and the activation of IRS-1 phosphorylation is also ER-dependent. Taken together, our results suggest that Rg1 not only increases IGF-IR expression but also enhances IGF-IR-mediated signaling pathways in MCF-7 cells. The stimulation of IGF-IR expression by Rg1 in MCF-7 cells appears to require ER, and its actions might involve ligand-independent activation of ER.

Plastic wastes constitute a worldwide environmental problem, and the demand for biodegradable plastics has become high. One of the most important characteristics of microbial polyesters is that they are thermoplastic with environmentally degradable properties. In this study, pUC19/PHA was cloned and transformed into three different Escherichia coli strains. Among the three strains that were successfully expressed in the production of polyhydroxyalkanoates (PHA), E. coli HMS174 had the highest yield in the production of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) (P[HB-HV]). The cell dry weight and PHA content of recombinant HMS174 reached as high as 10.27 g/L and 43% (w/w), respectively, in fed-batch fermentor culture. The copolymer of PHA, P(HB-HV), was found in the cells, and the biopolymers accumulated were identified and analyzed by gas chromatography, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. We demonstrated clearly that the E. coli host for PHA production has to be carefully selected to obtain a high yield. The results obtained indicated that a superior E. coli with high PHA production can be constructed with a desirable ratio of P(HB-HV), which has potential applications in industry and medicine.

Protein folding can be described in terms of the development of specific contacts between residues as a highly disordered polypeptide chain converts into the native state. Here we describe an NMR based strategy designed to detect such contacts by observation of nuclear Overhauser effects (NOEs). Experiments with alpha-lactalbumin reveal the existence of extensive NOEs between aromatic and aliphatic protons in the archetypal molten globule formed by this protein at low pH. Analysis of their time development provides direct evidence for near-native compactness of this state. Through a rapid refolding procedure the NOE intensity can be transferred efficiently into the resolved and assigned spectrum of the native state. This demonstrates the viability of using this approach to map out time-averaged interactions between residues in a partially folded protein.

An approach is described to monitor directly at the level of individual residues the formation of structure during protein folding. A two-dimensional heteronuclear nuclear magnetic resonance (NMR) spectrum was recorded after the rapid initiation of the refolding of a protein labeled with nitrogen-15. The intensities and line shapes of the cross peaks in the spectrum reflected the kinetic time course of the folding events that occurred during the spectral accumulation. The method was used to demonstrate the cooperative nature of the acquisition of the native main chain fold of apo bovine alpha-lactalbumin. The general approach, however, should be applicable to the investigation of a wide range of chemical reactions.

A simplified computer-based structural analysis procedure has been developed for evaluating the stresses in a lower limb prosthetic socket when subjected to external loads. This technique has been tested by studying a simple linear axisymmetric shell subjected to uniform loads. It was found that the stress and strain distribution obtained are close to those determined by a finite element technique. The method that has been proposed involves an incremental procedure, which can be used to analyse the behaviour of a prosthetic socket of irregular shape made from non-linear anisotropic materials. By employing the proposed procedure to study an example, in which a simplified lower limb prosthetic socket is subject to internal pressure and frictional forces, the effects of the material non-linearity have been found to be significant.

The transmission characteristics of a high-power CO(2)-laser beam through a single water aerosol particle are studied. It is found that before the onset of plasma formation there is a sizable range of laser intensity where the medium becomes almost totally transparent. A plausible argument for this induced transparency is given in terms of particle disintegration. This effect may have applications in laser atmospheric propagation.