TONs of copper fun: There is considerable interest in developing catalysts to harness the abundant natural supply of methane for various industrial applications. Two tricopper complexes capable of ...mediating efficient oxidation of methane to methanol under ambient conditions were tested: a biomimetic tricopper complex (see figure) and a tricopper‐peptide species derived from the particulate methane monooxygenase (pMMO) protein.
A pocketful of coppers: Redox potentiometry and EPR experiments have confirmed that the active site of the particulate methane monooxygenase (pMMO), a membrane‐bound enzyme that hydroxylates methane ...to methanol under ambient conditions, consists of one trinuclear copper cluster (see picture) and one type 2 copper site, in addition to the dinuclear copper cluster revealed previously by X‐ray crystallography.
Benozophenone (BP) type UV filters are extensively used in the personal care products to provide protection against the harmful effects of UV radiation. BPs are one of the primary components in the ...UV filter family, in which benophenone-2 (BP2) is widely used as a UV filter reagent in the sunscreen. Humans used these personal care products directly on skin and the chemicals will be washed away to the water system. BP2 has been identified as one of the endocrine disruptor chemicals, which can inference the synthesis, metabolism, and action of endogenous hormones. Environmentally, it has been found to contaminate water worldwide. In this study, we aimed to unfold the possible developmental toxicology of this chemical. Zebrafish are used as the screening model to perform in situ hybridization staining to investigate the effects of BP2 on segmentation, brain regionalization, and facial formation at four developmental stages (10–12 somite, prim-5, 2 and 5 days post-fertilization). Results showed 40 μM (9.85 mg L−1) or above BP2 exposure in zebrafish embryos for 5 days resulted in lipid accumulation in the yolk sac and facial malformation via affecting the lipid processing and the expression of cranial neural crest cells respectively. To conclude, the study alarmed its potential developmental toxicities at high dosage exposure.
•Low dose (<20 μM) BP2 exposure for 5 days do not alter the general embryogenesis in zebrafish embryos.•Dosages higher than 40 μM BP2 exposure resulted in developmental defects.•BP2 affects the segmentation process, blood circulation, lipid metabolism, and facial formation.
To evaluate the efficacy and safety of a new generation of 2.45-GHz microwave to ablate hepatocellular carcinoma by surgical approach. DESIGN; Case series with prospective follow-up.
A university ...teaching hospital in Hong Kong.
From March 2009 to January 2011, 26 consecutive patients (19 men and 7 women) with a median age of 63 (range, 49-79) years with hepatocellular carcinoma were recruited. Five (19%) of the patients had recurrent hepatocellular carcinoma after previous treatment.
Microwave ablation for hepatocellular carcinomas (one tumour, n=24; two tumours, n=2) using a laparoscopic (n=16) or open approach (n=10).
Operative mortality and morbidity, rate of incomplete ablation, recurrence rate, and survival rate.
The median tumour diameter was 3.8 cm (range, 2.0-6.0 cm). Complications occurred in five (19%) of the patients; only one was ablation-related, and there was no operative mortality. One (4%) of the patients experienced incomplete ablation. Recurrent tumours were noted in 11 (42%) of the patients (5 were local, 2 were remote, and 4 were multifocal) after a median follow-up of 14 (range, 4-26) months. The failure rate for local disease control was 23%, and was 14% if patients with recurrent hepatocellular carcinoma were excluded. All but one patient survived until the time of censorship. The mean survival was 25 (standard deviation, 1) months.
This new-generation microwave technique is safe and effective for local ablation of hepatocellular carcinoma. It is a valuable treatment option for patients who are not candidates for hepatectomy.
Herein, we report the lead optimization of amrinone–phenylalanine based GPR142 agonists. Structure–activity relationship studies led to the discovery of aminopyrazole–phenylalanine carboxylic acid ...22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.
Patients who have cystic fibrosis (CF) and experience delayed diagnosis by traditional methods have greater nutritional insult compared with peers diagnosed via neonatal screening. The objective of ...this study was to evaluate cognitive function in children with CF and the influence of both early diagnosis through neonatal screening and the potential effect of early malnutrition.
Cognitive assessment data were obtained for 89 CF patients (aged 7.3-17 years) during routine clinic visits. Patients had been enrolled in either the screened (N = 42) or traditional diagnosis (control) group (N = 47) of the Wisconsin CF Neonatal Screening Project. The Test of Cognitive Skills, Second Edition was administered to generate the Cognitive Skills Index (CSI) and cognitive factor scores (Verbal, Nonverbal, and Memory).
Cognitive scores in the overall study population were similar to normative data (CSI mean standard deviation: 102.5 16.6; 95% confidence interval: 99.1-105.9). The mean (standard deviation) CSI scores for the screened and control groups were 104.4 (14.4) and 99.8 (18.5), respectively. Significantly lower cognitive scores correlated with indicators of malnutrition and unfavorable family factors such as single parents, lower socioeconomic status, and less parental education. Our analyses revealed lower cognitive scores in patients with low plasma alpha-tocopherol (alpha-T) levels at diagnosis. In addition, patients in the control group who also had vitamin E deficiency at diagnosis (alpha-T < 300 microg/dl) showed significantly lower CSI scores in comparison with alpha-T-sufficient control subjects and both deficient and sufficient alpha-T subsets of screened patients.
Results suggest that prevention of prolonged malnutrition by early diagnosis and nutritional therapy, particularly minimizing the duration of vitamin E deficiency, is associated with better cognitive functioning in children with CF.
The objective of our study was to determine the usefulness of the diffusion-weighted magnetic resonance imaging and proton magnetic resonance spectroscopy (H-MRS) of hepatic malignancies for the ...assessment of response to locoregional treatment.
Forty-four patients (29 men; mean age, 58 years) with hepatic malignancies were treated locally. Magnetic resonance imaging examinations obtained before and at 1 and 6 months after transarterial chemoembolization were analyzed retrospectively. Imaging criteria included change in tumor size, percentage of enhancement in the arterial and portal venous phases, diffusion-weighted magnetic resonance imaging apparent diffusion coefficients, and choline concentration by quantitative H-MRS. Response to treatment was grouped according to RECIST (Response Evaluation Criteria in Solid Tumors) and European Association for the Study of the Liver (EASL) criteria based on magnetic resonance imaging at 6 months after treatment. Statistical analysis used paired t test, Fisher exact test, and univariate and multivariate Cox proportional hazards models.
Before treatment, the median tumor diameter was 6 cm; at 6 months after treatment, median tumor diameter was 5.1 cm. According to RECIST and EASL, 66% of the patients achieved partial response, 31% had stable disease, and 3% of the patients showed progressive disease. One month after transarterial chemoembolization, apparent diffusion coefficient increased (P < 0.14), and mean choline concentration of the tumors decreased (P < 0.008).
Diffusion-weighted imaging and hepatic choline levels by H-MRS could predict response to locoregional therapy.
It is unclear why some patients with cystic fibrosis (CF) succeed ("responders") in recovering from malnutrition and growth faltering after treatment initiation whereas others fail to do so ...("nonresponders"). We conducted a study to test the hypothesis that sustained high energy intake (increased EN) and normal plasma essential fatty acid status are critical determinants of treatment responsiveness within 2 years after diagnosis of CF.
A total of 71 CF children who had pancreatic insufficiency but not meconium ileus and were enrolled in the Wisconsin CF Neonatal Screening Project were studied. Responders were defined by having achieved adequate weight gain, as indicated by a recovery of weight z score (Wtz) comparable to Wtz at birth (WtzBR) within 2 years of diagnosis. Increased EN and sustained normal plasma linoleic acid level (increased pLA) were defined by achieving energy intake > or =120% of estimated requirement for > or =75% of the time and maintaining plasma LA > or =26% of total fatty acids for > or =75% of the time, respectively.
Thirty-two (68%) screened patients and 13 (54%) patients whose CF was diagnosed conventionally recovered WtzBR within 2 years of diagnosis. Screened patients responded at significantly younger ages (mean/median: 6.3/4.3 months) than patients whose CF was diagnosed conventionally (mean/median: 15.8/11.8 months). Proportionately fewer screened patients (33%) achieved increased EN compared with patients whose CF was diagnosed conventionally (73%). However, more screened patients responded to increased EN and recovered WtzBR (91%) than patients whose CF was diagnosed conventionally (56%), although this difference was of borderline significance. Compared with having neither increased EN nor increased pLA, the likelihood of being a responder was greatest with combined increased EN and increased pLA, followed by increased EN only. The positive associations between increased EN and increased pLA to treatment responsiveness remained significant after adjustment for neonatal screening status, baseline height and weight status, and indices of pulmonary disease severity.
Increased EN and increased pLA are critical in promoting adequate weight gain in children with newly diagnosed CF.
Zwei Trikupfer‐Komplexe wurden entwickelt, die die effiziente Oxidation von Methan zu Methanol unter Umgebungsbedingungen vermitteln: ein biomimetischer Trikupfer‐Komplex (siehe Bild) und eine von ...der Methan‐Monooxygenase (pMMO) abgeleitete Trikupferpeptid‐Spezies.
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