-
IUCrData Jan 2024In the title complex, [Ni(CHN)](CFSO)·(CHCH)O, the central Ni atom is sixfold coordinated by three nitro-gen atoms of each 2,6-bis-(2-benzimidazol-yl)pyridine ligand in...
In the title complex, [Ni(CHN)](CFSO)·(CHCH)O, the central Ni atom is sixfold coordinated by three nitro-gen atoms of each 2,6-bis-(2-benzimidazol-yl)pyridine ligand in a distorted octa-hedral geometry with two tri-fluoro-methane-sulfonate ions and a mol-ecule of diethyl ether completing the outer coordination sphere of the complex. Hydrogen bonding contributes to the organization of the asymmetric units in columns along the axis generating a porous supra-molecular structure. The structure was refined as a two-component twin with a refined BASF value of 0.4104 (13).
PubMed: 38322034
DOI: 10.1107/S2414314624000889 -
MSphere Oct 2019Gellan gum is a microbial exopolysaccharide, produced after aerobic fermentation using the Gram-negative bacterium strain ATCC 31461. Due to its unique structure and...
Gellan gum is a microbial exopolysaccharide, produced after aerobic fermentation using the Gram-negative bacterium strain ATCC 31461. Due to its unique structure and excellent physical characteristics, gellan gum has a broad range of applications in food, pharmaceutical, and other industries where it is used for stabilizing, emulsifying, thickening, and suspending. During the fermentative production of gellan, strain ATCC 31461 also accumulates large amounts of the metabolic by-products yellow carotenoid pigments and poly-β-hydroxybutyrate (PHB), which is decreasing the gellan production and increasing processing costs. A pigment PHB-free mutant was obtained by knocking out the phytoene desaturase gene () in the carotenoid biosynthetic pathway and the gene, encoding a PHB synthase for the polymerization of PHB. Unfortunately, the double gene knockout mutant produced only 0.56 g liter gellan. Furthermore, blocking PHB and carotenoid synthesis resulted in the accumulation of pyruvate, which reduced gellan production. To elevate gellan production, combined UV irradiation and ethyl methanesulfonate (EMS) mutagenesis treatment were used. A mutant strain with the same level of pyruvate as that of the wild-type strain and higher gellan production was isolated (1.35 g liter, 132.8% higher than the double gene knockout mutant and 14.4% higher than the wild-type strain ATCC 31461). In addition, a new gellan gum recovery method based on the new mutant strain was investigated, in which only 30% isopropanol was required, which is twice for the wild-type strains, and the performance of the final product was improved. Thus, the mutant strain could be an ideal strain for the commercial production of gellan. A carotenoid- and PHB-free double gene knockout strain mutant was constructed to simplify the purification steps normally involved in gellan production. However, the production of gellan gum was unexpectedly reduced. A mutant with 14.4% higher gellan production than that of the wild-type strain was obtained and isolated after employing UV and EMS combined mutagenesis. Based on this high-yield and low-impurity-producing mutant, a new recovery method requiring less organic solvent and fewer operating steps was developed. This method will effectively reduce the production costs and improve the economic benefits of large-scale gellan production.
Topics: Carotenoids; Ethyl Methanesulfonate; Fermentation; Gene Knockout Techniques; Hydroxybutyrates; Industrial Microbiology; Mutation; Polyesters; Polysaccharides, Bacterial; Sphingomonas; Ultraviolet Rays
PubMed: 31619503
DOI: 10.1128/mSphere.00668-19 -
Current Allergy and Asthma Reports Nov 2019Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments... (Review)
Review
PURPOSE OF REVIEW
Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID.
RECENT FINDINGS
Conventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far. Reduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.
Topics: Busulfan; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Primary Immunodeficiency Diseases; Transplantation Conditioning; Vidarabine
PubMed: 31741098
DOI: 10.1007/s11882-019-0883-1 -
Annals of Hematology Jun 2022Reduced intensity conditioning (RIC) and reduced toxicity conditioning (RTC) regimens enable allogeneic hematopoietic stem cell transplantation (alloSCT) to more...
Conditioning with fludarabine and treosulfan compared to FLAMSA-RIC in allogeneic stem cell transplantation for myeloid malignancies: a retrospective single-center analysis.
Reduced intensity conditioning (RIC) and reduced toxicity conditioning (RTC) regimens enable allogeneic hematopoietic stem cell transplantation (alloSCT) to more patients due to reduction in transplant-related mortality (TRM). The conditioning regimens with fludarabine and treosulfan (Flu/Treo) or fludarabine, amsacrine, cytarabine (FLAMSA)-RIC have shown their efficacy and tolerability in various malignancies. So far, no prospective study comparing the two regimens is available. Two studies compared the regimens retrospectively, in which both provided similar outcome. In this retrospective, single-center analysis, these two regimens were compared with regard to outcome, rate of acute and chronic graft versus host disease (GvHD), and engraftment. 113 consecutive patients with myeloid malignancies who received Flu/Treo or FLAMSA-RIC conditioning prior to alloSCT between 2007 and 2019 were included. Except for age, previous therapies, and remission status before alloSCT, patient characteristics were well balanced. The median follow-up time within this analysis was 44 months. There was no significant difference in absolute neutrophil count (ANC) or platelet engraftment between the two conditioning regimens. Overall survival (OS), the relapse-free survival (RFS), and the TRM were not significantly different between the two cohorts. The rate of GvHD did not differ between the two groups. In summary, this retrospective analysis shows that there is no major difference regarding tolerability and survival between the Flu/Treo and FLAMSA-RIC regimens. Despite several limitations due to uneven distribution concerning age and remission status, we demonstrate that Flu/Treo and FLAMSA-RIC provide similar outcomes and are feasible in older and intensively pre-treated patients.
Topics: Aged; Busulfan; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Neoplasm Recurrence, Local; Retrospective Studies; Transplantation Conditioning; Vidarabine
PubMed: 35364726
DOI: 10.1007/s00277-022-04822-x -
The Journal of Prevention of... 2022Hydromethylthionine mesylate is a tau aggregation inhibitor shown to have exposure-dependent pharmacological activity on cognitive decline and brain atrophy in two... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral Tau Aggregation Inhibitor for Alzheimer's Disease: Design, Progress and Basis for Selection of the 16 mg/day Dose in a Phase 3, Randomized, Placebo-Controlled Trial of Hydromethylthionine Mesylate.
BACKGROUND
Hydromethylthionine mesylate is a tau aggregation inhibitor shown to have exposure-dependent pharmacological activity on cognitive decline and brain atrophy in two completed Phase 3 trials in mild/moderate Alzheimer's disease (AD).
OBJECTIVES
The present report summarises the basis for selection of 16 mg/day as monotherapy as the optimal treatment regime and the design rationale of a confirmatory Phase 3 trial (LUCIDITY).
DESIGN
The trial comprises a 12-month double-blind, placebo-controlled phase followed by a 12-month modified delayed-start open-label treatment phase.
SETTING
76 clinical research sites in North America and Europe.
PARTICIPANTS
545 patients with probable AD or MCI-AD in the final version of the protocol.
INTERVENTION
Participants were assigned randomly to receive hydromethylthione mesylate at doses of 16 mg/day, 8 mg/day or placebo at a 4:1:4 ratio during the double-blind phase. All participants in the open-label phase receive the 16 mg/day dose.
MEASUREMENTS
Co-primary clinical outcomes are the 11-item Alzheimer's Disease Assessment Scale (ADAS-cog11) and the 23-item Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23). Secondary biomarker measures include whole-brain atrophy and temporal lobe 18F-fluorodeoxyglucose positron emission tomography.
RESULTS
446 participants are expected to complete the 12-month placebo-controlled phase in March 2022.
CONCLUSIONS
If the primary end points are met, the data will provide confirmatory evidence of the clinical and biomarker benefits of hydromethylthionine mesylate in minimal to moderate AD. As low-dose oral hydromethylthionine mesylate is simple to use clinically, does not cause amyloid-related imaging abnormalities and has a benign safety profile, it would likely improve AD management.
Topics: Humans; Alzheimer Disease; Activities of Daily Living; Fluorodeoxyglucose F18; Atrophy; Mesylates
PubMed: 36281683
DOI: 10.14283/jpad.2022.63 -
Scientific Reports Nov 2020Qatar has the third-largest natural gas reserves in the world and is the second largest Liquefied natural gas (LNG) exporter in the world. These reserves are mainly...
Qatar has the third-largest natural gas reserves in the world and is the second largest Liquefied natural gas (LNG) exporter in the world. These reserves are mainly located in its offshore North Field where the gas is extracted, transported to the onshore units, and is converted to LNG for international export. The formation of natural gas hydrates in the offshore subsea lines can cause unwanted blockages and hinder the smooth supply of gas supply from offshore to onshore units. In the present work, the formation and dissociation of methane gas hydrates have been studied in the ultra pure water system (UPW), artificial seawater (ASW), and Qatar seawater (QSW) at different conditions (4-10 MPa) using standard rocking cell rig. The naturally occurring seawater was collected from Ras Laffan seacoast located in Doha, Qatar. The seawater sample was examined for elemental analysis (SO, Cl, Na, Ca, Mg, K, and Fe) using inductively coupled plasma atomic emission spectroscopy (ICP-AES) technique and its other properties like density, electrical conductivity, and pH were also measured. The experimental results show that the CH pure water HLVE curve is suppressed by about 3 K in Qatar seawater and 2 K in artificial seawater. The hydrate inhibition strength of the Ionic liquids (ILs) salts 3-Ethyl-1-methyl-1H-imidazol-3-ium methane-sulfonate [CHNOS] and 3-Ethyl-1-methyl-1H-imidazol-3-ium dicyanoazanide [CHN] was evaluated in both the ultra pure water and Qatar seawater systems. Their performance was compared with methanol and other ILs salts reported in the literature. The selected ILs exhibited poor hydrate inhibition effect in the ultra pure water systems, but they show a noticeable thermodynamic and kinetic hydrate inhibition effect in the Qatar seawater system. The computational 3D molecular models of ILs and methanol were generated to cognize the plausible hydrate inhibition mechanism in the presence of these inhibitors.
PubMed: 33173116
DOI: 10.1038/s41598-020-76443-1 -
Journal of Chromatography. A Jan 2022Research on oligosaccharides, including the complicated product mixtures generated by lytic polysaccharide monooxygenases (LPMOs), is growing at a rapid pace. LPMOs are...
Research on oligosaccharides, including the complicated product mixtures generated by lytic polysaccharide monooxygenases (LPMOs), is growing at a rapid pace. LPMOs are gaining major interest, and the ability to efficiently and accurately separate and quantify their native and oxidized products chromatographically is essential in furthering our understanding of these oxidative enzymes. Here we present a novel set of methods based on dual electrolytic eluent generation, where the conventional sodium acetate/sodium hydroxide (NaOAc/NaOH) eluents in high-performance anion-exchange chromatography (HPAEC) are replaced by electrolytically-generated potassium methane sulfonate/potassium hydroxide (KMSA/KOH). The new methods separate all compounds of interest within 24-45 min and with high sensitivity; limits of detection and quantification were in the range of 0.0001-0.0032 mM and 0.0002-0.0096 mM, respectively. In addition, an average of 3.5 times improvement in analytical CV was obtained. This chromatographic platform overcomes drawbacks associated with manual preparation of eluents and offers simplified operation and rapid method optimization, with increased precision for less abundant LPMO-derived products.
Topics: Cellulose; Mixed Function Oxygenases; Oligosaccharides; Oxidation-Reduction; Polysaccharides
PubMed: 34894418
DOI: 10.1016/j.chroma.2021.462691 -
Transplantation and Cellular Therapy Jan 2021We report the outcomes of cord blood transplantation (CBT) with a busulfan (Bu) pharmacokinetics-targeted myeloablative conditioning regimen in 97 children with Hurler...
We report the outcomes of cord blood transplantation (CBT) with a busulfan (Bu) pharmacokinetics-targeted myeloablative conditioning regimen in 97 children with Hurler syndrome (HS) performed between 2004 and 2016. The median age at CBT was 10.8 months (range, 0.23 to 63.2 months). The median duration of follow-up for surviving patients was 4.2 years (range, 1.0 to 12.8 years). Five-year overall survival (OS) and engrafted survival (ES) were 88% and 79%, respectively. OS was 95% in patients who received Bu/fludarabine (Flu)/antithymocyte globulin (ATG) conditioning, 90% in those who received Bu/cyclophosphamide (Cy)/ATG, and 74% in those who received Bu/Cy/alemtuzumab (P = .02). ES was 84% for recipients of Bu/Flu/ATG conditioning, 83% for recipients of Bu/Cy/ATG conditioning, and 65% for recipients of Bu/Cy/alemtuzumab conditioning (P = .34). Receipt of washed CB units (P = .03) and HLA matching ≤6/10 (P = .02) were associated with significantly lower ES. The 1-year cumulative incidence of graft failure was 11% (95% confidence interval, 6% to 21%). Five patients (5%) had grade III-IV acute GVHD, 5 patients had limited chronic GVHD, and 1 patient had extensive GVHD. The incidence of veno-occlusive disease was higher in patients conditioned with Bu/Cy compared with those conditioned with Bu/Flu (19% [n = 10] versus 5% [n = 2]: P = .03). Of the 11 patients with graft failure, 8 (73%) were aplastic, and 3 (27%) had autologous reconstitution. Of 11 patients with graft failure, 9 underwent a second CBT, and 8 (89%) survived. Full donor chimerism was observed in 89% patients after first CBT and in all patients after second CBT. Survival after CBT for HS has improved, but better strategies are still needed to improve graft outcomes.
Topics: Busulfan; Child; Cord Blood Stem Cell Transplantation; Humans; Mucopolysaccharidosis I; Retrospective Studies; Transplantation Conditioning
PubMed: 32961374
DOI: 10.1016/j.bbmt.2020.08.033 -
Blood Advances May 2020Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic...
Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation-approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti-T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.
Topics: Animals; Busulfan; Hematopoietic Stem Cell Transplantation; Humans; Lymphohistiocytosis, Hemophagocytic; Neoplasm Recurrence, Local; Rabbits; Transplantation Conditioning
PubMed: 32384542
DOI: 10.1182/bloodadvances.2020001748 -
Plant Biotechnology Journal Jun 2024Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in...
Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in cucurbits remain unclear. In this study, we identified a cucumber (Cucumis sativus) compact plant architecture (cpa1) mutant from an ethyl methane sulfonate (EMS)-mutagenized library that exhibited distinctive phenotypic traits, including reduced leaf petiole angle and leaf size. The candidate mutation causes a premature stop codon in CsaV3_1G036420, which shares similarity to Arabidopsis HOOKLESS 1 (HLS1) encoding putative histone N-acetyltransferase (HAT) protein and was named CsHLS1. Consistent with the mutant phenotype, CsHLS1 was predominantly expressed in leaf petiole bases and leaves. Constitutive overexpressing CsHLS1 in cpa1 restored the wild-type plant architecture. Knockout of CsHLS1 resulted in reduces leaf petiole angle and leaf size and as well as decreased acetylation levels. Furthermore, CsHLS1 directly interacted with CsSCL28 and negatively regulated compact plant architecture in cucumber. Importantly, CsHLS1 knockout increased the photosynthesis rate and leaf nitrogen in cucumbers, thereby maintaining cucumber yield at normal density. Overall, our research provides valuable genetic breeding resource and gene target for creating a compact plant architecture for dense cucumber planting.
Topics: Cucumis sativus; Plant Proteins; Plant Leaves; Gene Expression Regulation, Plant; Photosynthesis; Mutation; Histone Acetyltransferases
PubMed: 38261466
DOI: 10.1111/pbi.14298