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The dominant O -> Ni CT transition of [(PhTt(super tBu))2Ni2(mu-O)2] observed at 17700 cm(super -1) is red-shifted by ~7000 cm(super -1) relative to the corresponding transition in bis-mu-oxo(Ni(super 3+))2 dimers with nitrogen supporting ligands. This red-shift along with a relatively low Ni-O bond strength are primarily due to the presence of the thioether ligands in [(PhTt(super tBu))2Ni2(mu-O)2] that directly influence the characters of the Ni2O2 core MOs.

The catalytic oxidation of thioanisole (PhSMe) to sulfoxide (PhS(O)Me) with iodosylbenzene (PhIO) as the oxygen source and Mn(III) triazacorrole as added catalyst is stated. A novel PhIO-Mn(V)O adduct is most likely the active oxidizing species in the catalytic mechanism.

Research has been conducted on Ni (super)+ four-coordinate complex. Results demonstrate that this complex serves as a Ni-CO reaction intermediate in the acetyl-CoA synthase catalytic cycle.

A remarkably stable manganese(V)-Oxo corrolazine complex was synthesized using a corrolazine ligand. The extraordinary stability of this complex has allowed for complete characterization, including the first resonance Raman Spectra.

The four-coordinate Ni[sup +] complex [PhTt[sup tBu]]Ni[sup I]CO, where PhTt[sup tBu] = phenyltris((tert-buthylthio)methyl)borate (a tridentate thioether donor ligand), serves as a possible model for key Ni-CO reaction intermediates in the acetyl-CoA synthase (ACS) catalytic cycle. Resonance Raman, electronic absorption, magnetic circular dichroism (MCD), variabletemperature variable-field MCD, and electron paramagnetic resonance spectroscopies were utilized in conjunction with density functional theory and semiemperical INDO/S-Cl calculations to investigate the ground and excited states of [PhTt[sup tBu]]Ni[sup I]CO. These studies reveal extensive Ni[sup +] → CO π-back-bonding interactions, as evidenced by a low C-O stretching frequency (1995 cm[sup -1]), a calculated C-O stretching force constant of 15.5 mdyn/Å (as compared to k[sub CO](free CO) = 18.7 mdyn/Å), and strong Ni[sup +] → CO charge-transfer absorption intensities. Calculations reveal that this high degree of π-back-bonding is due to the fact that the Ni[sup +] 3d orbitals are in close energetic proximity to the CO π[sup *] acceptor orbitals. In the ACS "paramagnetic catalytic cycle", the high degree of π-backbonding in the putative Ni[sup +]-CO intermediate (the NiFeC species) is not expected to preclude methyl transfer from CH[sub 3]-CoFeSP. [ABSTRACT FROM AUTHOR]

Spectroscopic and density functional theory (DFT) electronic structure computational studies on a binuclear bis-µ-oxo bridged (Ni[sup 3+])[sub 2] complex, [(PhTt[sub Bu])[sub 2]Ni[sub 2](µ-O)[sub 2]] (1), where (PhT[sup Bu]) represents phenyltris((tert-butylthio)methyl)borate, are presented and discussed. These studies afford a detailed description of the Ni[sub 2]O[sub 2] core electronic structure in bis-µ-oxo (Ni[sup 3+])[sub 2] dimers and provide insight into the possible role of the (PhT[sup Bu]) thioether ligand in the formation of 1 from a Ni[sup 1+] precursor by O[sub 2] activation. From a normal coordinate analysis of resonance Raman data, a value of k[sub Ni-O] = 2.64 mdyn/Å is obtained for the Ni-O stretch force constant for 1. This value is smaller than k[sub Cu-o] = 2.82-2.90 mdyn/Å, obtained for bis-µ-oxo (Cu[sup 3+])[sub 2] dimers possessing nitrogen donor ligands, indicating a reduced metal-oxo bond strength in 1. Electronic absorption and magnetic circular dichroism spectroscopic techniques permit identification of several O→Ni and S→Ni charge transfer (CT) transitions that are assigned on the basis of DFT calculations. The dominant O→Ni CT transition of I occurs at 17 700 cm[sup -1], red-shifted by ∼7000 cm[sup -1] relative to the corresponding transition in bis-µ-oxo (Ni[sup 3+])[sub 2] dimers with nitrogen donor ligands. This red-shift along with the relatively low value of k[sub Ni-O] are due primarily to the presence of the thioether ligands in I that greatly affect the compositions of the Ni[sub 2]O[sub 2] core MOs. This unique property of the thioether ligand likely contributes to the reactivity of the Ni center in the precursor [(PhTt[sup tBu])Ni[sup 1+]CO] toward O[sub 2]. DFT computations reveal that conversion of a hypothetical side-on peroxo (Ni[sup 2+])[sub 2] dimer, [(PhT[sub tBu])[sub 2]Ni[sub 2](µ-η²:η²-O[sub 2])], to the bis-µ-oxo (Ni[sup... [ABSTRACT FROM AUTHOR]

A major goal in understanding the mechanism of synthetic and naturally occurring metalloporphyrin-catalyzed oxidations has been to identify the structures of the reactive intermediates, with particular attention given to cytochrome P450-type processes such as sulfoxidation, epoxidation, and hydroxylation. The importance of high-valent metal-oxo species in such oxygenation chemistry is well-established, although typically these species are short-lived and difficult to observe directly. This study provides the first evidence for a high-valent metal-oxo porphyrinoid species acting as a Lewis acid catalyst in the same way as the proposed (porph)-M(III) species I does.

Reports on the spectroscopic analysis of a nickel (Ni) thioether complex produced by oxygenation of a Ni precursor. Characterization of Ni coordination sphere in [(PhTt[sup tBu])Ni][sub 2](mu-O)[sub 2]; Ligand positions that are potential targets for oxidation; Effect of the nickel complex on oxygen=oxygen bond rupture.

Examines the support of thioether ligation for the organometallic cobalt and nickel complexes. Combination of ligand in biological and industrial catalysis; Design of preparative manipulations using chlorides derivatives; Coordination of borato ligand in the bidentate mode.

Examines the electronic structure of nickel coordination complexes using 1s2p X-ray resonance Raman spectroscopy. Electronic ground state; Valence electron excitations; Sensitivity of the spectroscopy.

Background: Acute Hepatic Porphyria is a group of four rare genetic but treatable diseases that often go undiagnosed due to its non-specific symptoms, under-recognition of the condition by clinicians, and the lack of access to specialists and appropriate testing. This case-control study investigates the phenotypic and demographic patterns in Acute Hepatic Porphyria (AHP) patients at a tertiary care center (University of California Los Angeles) to update recommendations for recognition and diagnosis of this disease in our community., Method: A retrospective chart analysis was conducted on 45 patients who were evaluated for AHP, Electronic Medical Record (EMR) data was collected and analyzed to investigate clinical differences and correlations., Results: 27 patients tested positive for AHP through urinary metabolites and confirmatory genetic testing and 18 patients tested negative; of those, 16 patients received a definite alternative diagnosis. Hashimoto's, T1DM (Type 1 Diabetes Mellitus), Fibromyalgia and cannabinoid use with cyclic vomiting syndrome were negatively correlated with AHP, while psychiatric disorders and OBGYN disorders were positively correlated with AHP. The highest rate of diagnosis resulted from a combination of genetic and biochemical testing. Testing outside of an acute attack was not associated with a positive diagnosis., Conclusions: Patients with a history of OBGYN disorders and psychiatric disorders may be at increased risk of having AHP, yet there is a lack of involvement of these specialties in the diagnosis and care of AHP, in addition to a lack of studies investigating AHP in non-white populations potentially leading to reduced recognition of AHP., Competing Interests: VR receives grant funding from Alnylam, Genentech, Merck, Takeda, Blueprint Medicines, Stryker, and Mitsubishi Tanabe. The authors declare that no actual conflicts of interest exist. The other authors hereby declare that they have no potential competing conflicts of interest.

Worldwide, Po-210 is an important contributor to human ionising radiation exposure through food. To characterise the ionising radiation dose for New Zealanders from Po-210 in shellfish, a dose assessment was undertaken. Deterministic and probabilistic dietary models were constructed by assigning shellfish consumption rates to Po-210 activity concentrations measured in shellfish. Modelling was undertaken for different shellfish consumer populations and geographical areas. Dietary modelling estimated an annual dose range from 4 μSv to 6070 μSv. The lowest dose was calculated for the overall shellfish consumer population residing in areas where baseline Po-210 activity concentrations were measured in shellfish. The highest dose was calculated for the high shellfish consumer population residing in areas where elevated activity concentrations were measured in shellfish. For the majority of the New Zealand population, the total estimated dose did not exceed the selected reference level of 1000 μSv, and Po-210 is therefore not a cause of concern. About 50% of high shellfish consumers residing in areas where shellfish had elevated Po-210 activity concentrations were exposed to ionising radiation resulting in an annual dose higher than 1000 μSv. Exposure assessment for different demographic groups identified that higher shellfish consumption rates in the population identifying as Māori lead to higher doses of ionising radiation for this group., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics. We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangiopancreatography (ERCP)-confirmed choledocholithiasis and accordingly developed predictive machine learning models (MLMs)., Methods: Clinical data of consecutive patients undergoing first-ever ERCP for suspected choledocholithiasis from 2015-2019 were abstracted from a prospectively-maintained database. Multiple logistic regression was used to identify predictors of ERCP-confirmed choledocholithiasis. MLMs were then trained to predict ERCP-confirmed choledocholithiasis using pre-ERCP ultrasound (US) imaging only and separately using all available noninvasive imaging (US/CT/magnetic resonance cholangiopancreatography). The diagnostic performance of American Society for Gastrointestinal Endoscopy (ASGE) "high-likelihood" criteria was compared to MLMs., Results: We identified 270 patients (mean age 46 years, 62.2% female, 73.7% Hispanic/Latino, 59% with noninvasive imaging positive for choledocholithiasis) with native papilla who underwent ERCP for suspected choledocholithiasis, of whom 230 (85.2%) were found to have ERCP-confirmed choledocholithiasis. Logistic regression identified choledocholithiasis on noninvasive imaging (odds ratio (OR) = 3.045, P = 0.004) and common bile duct (CBD) diameter on noninvasive imaging (OR=1.157, P = 0.011) as predictors of ERCP-confirmed choledocholithiasis. Among the various MLMs trained, the random forest-based MLM performed best; sensitivity was 61.4% and 77.3% and specificity was 100% and 75.0%, using US-only and using all available imaging, respectively. ASGE high-likelihood criteria demonstrated sensitivity of 90.9% and specificity of 25.0%; using cut-points achieving this specificity, MLMs achieved sensitivity up to 97.7%., Conclusions: MLMs using age, sex, race, presence of diabetes, fever, body mass index (BMI), total bilirubin, maximum CBD diameter, and choledocholithiasis on pre-ERCP noninvasive imaging predict ERCP-confirmed choledocholithiasis with good sensitivity and specificity and outperform the ASGE criteria for patients with suspected choledocholithiasis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

The neurotransmitter levels of representatives from five different diagnosis groups were tested before and after participation in the MNRI ® -Masgutova Neurosensorimotor Reflex Intervention. The purpose of this study was to ascertain neurological impact on (1) Developmental disorders, (2) Anxiety disorders/OCD (Obsessive Compulsive Disorder), PTSD (Post-Traumatic Stress disorder), (3) Palsy/Seizure disorders, (4) ADD/ADHD (Attention Deficit Disorder/Attention Deficit Disorder Hyperactive Disorder), and (5) ASD (Autism Spectrum Disorder) disorders. Each participant had a form of neurological dysregulation and typical symptoms respective to their diagnosis. These diagnoses have a severe negative impact on the quality of life, immunity, stress coping, cognitive skills, and social assimilation. This study showed a trend towards optimization and normalization of neurological and immunological functioning, thus supporting the claim that the MNRI method is an effective non-pharmacological neuromodulation treatment of neurological disorders. The effects of MNRI on inflammation have not yet been assessed. The resulting post-MNRI changes in participants' neurotransmitters show significant adjustments in the regulation of the neurotransmitter resulting in being calmer, a decrease of hypervigilance, an increase in stress resilience, behavioral and emotional regulation improvements, a more positive emotional state, and greater control of cognitive processes. In this paper, we demonstrate that the MNRI approach is an intervention that reduces inflammation. It is also likely to reduce oxidative stress and encourage homeostasis of excitatory neurotransmitters. MNRI may facilitate neurodevelopment, build stress resiliency, neuroplasticity, and optimal learning opportunity. There have been no reported side effects of MNRI treatments.

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients., (Copyright © 2015 John Wiley & Sons, Ltd.)

Given the success in engineering synthetic phenotypes in microbes and mammalian cells, constructing non-native pathways in mammals has become increasingly attractive for understanding and identifying potential targets for treating metabolic disorders. Here, we introduced the glyoxylate shunt into mouse liver to investigate mammalian fatty acid metabolism. Mice expressing the shunt showed resistance to diet-induced obesity on a high-fat diet despite similar food consumption. This was accompanied by a decrease in total fat mass, circulating leptin levels, plasma triglyceride concentration, and a signaling metabolite in liver, malonyl-CoA, that inhibits fatty acid degradation. Contrary to plants and bacteria, in which the glyoxylate shunt prevents the complete oxidation of fatty acids, this pathway when introduced in mice increases fatty acid oxidation such that resistance to diet-induced obesity develops. This work suggests that using non-native pathways in higher organisms to explore and modulate metabolism may be a useful approach.

The liver X receptor alpha (LXRalpha) is a member of the nuclear hormone receptor superfamily that plays an important role in lipid homeostasis. Here we characterize two alternative human LXRalpha transcripts, designated LXRalpha2 and LXRalpha3. All three LXRalpha isoforms are derived from the same gene via alternative splicing and differential promoter usage. The LXRalpha2 isoform lacks the first 45 amino acids of LXRalpha1, and is generated through the use of a novel promoter and first exon. LXRalpha3 lacks 50 amino acids within the ligand binding domain and is generated through alternative recognition of the 3'-splice site in exon 6. LXRalpha2 and LXRalpha3 are expressed at lower levels compared with LXRalpha1 in most tissues, except that LXRalpha2 expression is dominant in testis. Both LXRalpha2 and LXRalpha3 heterodimerize with the retinoid X receptor and bind to LXR response elements. LXRalpha2 shows reduced transcriptional activity relative to LXRalpha1, indicating that the N-terminal domain of LXRalpha is essential for its full transcriptional activity. LXRalpha3 is unable to bind ligand and is transcriptionally inactive. These observations outline a previously unrecognized role for the N terminus in LXR function and suggest that the expression of alternative LXRalpha transcripts in certain biological contexts may impact LXR signaling and lipid metabolism.