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Conventional and also biodegradable polymer microplastics have started to be broadly present in the environment, if they end up in soil, they may influence both abiotic and biotic soil properties. In this study, the interactions of polyethylene wax together with three biodegradable polyesters PLA, PHB and PBAT with a soil matrix were investigated over a 1-year incubation period. Soil organic matter content was measured using UV-VIS, the microbial biomass amount was measured using qPCR, the mineralisation of polymers was measured using UGA 3000, the surface of polymers was observed with SEM, live/dead microorganisms were determined by fluorescent microscopy and microbial consortia diversity was analyzed using NGS. The amount of humic substances was generally higher in incubations with slowly degrading polyesters, but the effect was temporary. The microbial biomass grew during the incubations; the addition of PHB enhanced fungal biomass whereas PE wax enhanced bacterial biomass. Fungal microbial consortia diversity was altered in incubations with PHB and PBAT. Interestingly, these two polyesters were also covered in biofilm, probably fungal. No such trend was observed in a metagenomic analysis of bacteria, although, bacterial biofilm was probably formed on the PE520 surface. Different methods confirmed the effect of certain polymers on the soil environment.

Men have a higher risk of developing atrial fibrillation (AF) than women, though the reason for this is unknown. Here, we compared atrial electrical and structural properties in male and female mice and explored the contribution of sex hormones. Cellular electrophysiological studies revealed that action potential configuration, Na + and K + currents were similar in atrial myocytes from male and female mice (4-5 months). Immunofluorescence showed that male atrial myocytes had more lateralization of connexins 40 (63 ± 4%) and 43 (66 ± 4%) than females (Cx40: 45 ± 4%, p = 0.006; Cx43: 44 ± 4%, p = 0.002), with no difference in mRNA expression. Atrial mass was significantly higher in males. Atrial myocyte dimensions were also larger in males. Atrial fibrosis was low and similar between sexes. Orchiectomy (ORC) abolished sex differences in AF susceptibility (M: 65%; ORC: 38%, p = 0.050) by reducing connexin lateralization and myocyte dimensions. Ovariectomy (OVX) did not influence AF susceptibility (F: 42%; OVX: 33%). This study shows that prior to the development of age-related remodeling, male mice have more connexin lateralization and larger atria and atrial myocyte than females. Orchiectomy reduced AF susceptibility in males by decreasing connexin lateralization and atrial myocyte size, supporting a role for androgens. These sex differences in AF substrates may contribute to male predisposition to AF.

Background Elevated angiotensin II levels are thought to play an important role in atrial electrical and structural remodeling associated with atrial fibrillation. However, the mechanisms by which this remodeling occurs are still unclear. Accordingly, we explored the effects of angiotensin II on atrial remodeling using transgenic mice overexpressing angiotensin II type 1 receptor (AT1R) specifically in cardiomyocytes. Methods and Results Voltage-clamp techniques, surface ECG, programmed electrical stimulations along with quantitative polymerase chain reaction, Western blot, and Picrosirius red staining were used to compare the atrial phenotype of AT1R mice and their controls at 50 days and 6 months. Atrial cell capacitance and fibrosis were increased only in AT1R mice at 6 months, indicating the presence of structural remodeling. Ca 2+ ( I CaL ) and K + currents were not altered by AT1R overexpression (AT1R at 50 days). However, I CaL density and Ca V 1.2 messenger RNA expression were reduced by structural remodeling (AT1R at 6 months). Conversely, Na + current ( I Na ) was reduced (-65%) by AT1R overexpression (AT1R at 50 days) and the presence of structural remodeling (AT1R at 6 months) yields no further effect. The reduced I Na density was not explained by lower Na V 1.5 expression but was rather associated with an increase in sarcolemmal protein kinase C alpha expression in the atria, suggesting that chronic AT1R activation reduced I Na through protein kinase C alpha activation. Furthermore, connexin 40 expression was reduced in AT1R mice at 50 days and 6 months. These changes were associated with delayed atrial conduction time, as evidenced by prolonged P-wave duration. Conclusions Chronic AT1R activation leads to slower atrial conduction caused by reduced I Na density and connexin 40 expression.

Background: There continues to be an interest in minimally invasive approaches to pancreatic surgery. At our institution, there has been a progressive change from an open to minimally invasive surgery (MIS) (laparoscopic, robotic, or laparoscopic-robotic) approach for central pancreatectomies (CP). The aim of this study was to evaluate surgical outcomes with open CP (O-CP) versus minimally invasive CP (MI-CP)., Methods: A retrospective medical review of patients who underwent CP between 1993 and 2018 at Yonsei University Health System, Seoul, Korea was performed. Short-term perioperative outcomes were compared between O-CP and MI-CP., Results: Thirty-one CPs (11 open, 20 MIS) were identified during the study period. No difference was observed in admission days between O-CP and MI-CP (21.2 vs. 16.7 days, p = 0.340), although operating time was significantly increased in the MI-CP group (296.8 vs. 374.8 min, p = 0.036). Blood loss was significantly less in MI-CP vs. O-CP (807.1 vs. 214.0 mls, p = 0.001), with no difference in post-operative new-onset diabetes (9% vs. 5%). The overall post-operative pancreatic fistula rate was 25.8%, and no significant difference between O-CP and MI-CP or complication rates (45% vs. 40%) was observed., Conclusion: Despite increased operative time, MI-CP is feasible and comparable to conventional O-CP with regard to surgical outcomes in well-selected patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Polyethylene films are one of the most frequently used packaging materials in our society, due to their combination of strength and flexibility. An unintended consequence of this high use has been the ever-increasing accumulation of polyethylene films in the natural environment. Previous attempts to understand their deterioration have either focused on their durability using polymer analysis; or they have focused on changes occurring during outdoor exposure. Herein, this study combines those strategies into one, by studying the chemical and physical changes in the polyethylene structure in a laboratory using molecular weight and IR spectroscopic mapping analysis, combined with temperate UV-accelerated weathering cycles. This approach has been correlated to real-world outdoor exposure timeframes by parallel testing of the sample polyethylene films in Florida and France. The formation of polyethylene microparticles or polyethylene waxes is elucidated through comparison of drop point testing and molecular weight analysis.

Accelerated UV-weathering cycles are predominately used for evaluating the durability of plastic materials, particularly polyethylene (PE) films. The point of failure for this testing is usually the loss of a physical property, such as the loss of tensile strength over time. For plastics designed to be instable under environmental conditions, the accelerated weathering cycles are yet to be defined and their correlation to outdoor exposure has yet to be made. This study demonstrates the utility of a newly defined temperate accelerated UV-weathering cycle, recently codified in the British Standard PAS 9017:2020. In addition, the effectiveness of the laboratory weathering cycle has been correlated to real-world outdoor exposure through simultaneous testing of the same samples at a specialist outdoor exposure site in Florida. The utility of the testing methodology and the performance of the polyethylene samples was demonstrated through the use of High Temperature Gel Permeation Chromatography (HT-GPC) analysis. The data led to a detailed insight into the physico-chemical changes occurring in the PE films upon exposure to environmental stimuli. By comparison, and surprisingly, the techniques employed appear to provide an insight into the processes in which secondary micro-particles of PE are formed from macro-polyethylene samples. The temperate accelerated UV-weathering cycle over 14 days demonstrated an approximate correlation to 90 days of outdoor exposure in Florida for the PE film studied.

Natural sesquiterpene synthases have evolved to make complex terpenoids by quenching reactive carbocations either by proton transfer or by hydroxylation (water capture), depending on their active site. Germacradien-11-ol synthase (Gd11olS) from Streptomyces coelicolor catalyzes the cyclization of farnesyl diphosphate (FDP) into the hydroxylated sesquiterpene germacradien-11-ol. Here, we combine experiment and simulation to guide the redesign of its active site pocket to avoid hydroxylation of the product. Molecular dynamics simulations indicate two regions between which water molecules can flow that are responsible for hydroxylation. Point mutations of selected residues result in variants that predominantly form a complex nonhydroxylated product, which we identify as isolepidozene. Our results indicate how these mutations subtly change the molecular choreography in the Gd11olS active site and thereby pave the way for the engineering of terpene synthases to make complex terpenoid products., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Purpose: The da Vinci SP robotic surgical system (Intuitive Surgical) offers pure SP with 4 lumens, which accommodates the fully-wristed endoscope and 3 arms with multijoint feature. We herein present our initial experience of the da Vinci SP surgical system in robotic single-site cholecystectomy., Methods: Thirty consecutive patients with a preoperative diagnosis of gallstones and/or chronic cholecystitis who underwent robotic SP cholecystectomy (RSPC) using da Vinci SP surgical system from January to May 2019 were reviewed. The perioperative outcomes were assessed and compared with those performed using Si-robotic single-site surgical system., Results: Mean docking time was 5.2 minutes. The mean actual dissection time was 14.6 minutes while the mean operation time was 75.1 minutes. Postoperative course was unremarkable and patients were discharged after a mean hospital stay of 1.5 days. In comparative analysis, operation time (109.5 ± 30.0 minutes vs . 75.1 ± 17.5 minutes, P = 0.001), docking time (11.9 ± 4.3 minutes vs . 5.2 ± 1.9 minutes, P = 0.001), actual dissection time (34.6 ± 18.4 minutes vs . 14.6 ± 5.1 minutes, P = 0.001), console time (58.7 ± 23.0 minutes vs . 32.4 ± 11.6 minutes, P = 0.001), immediate postoperative pain (4.6 ± 1.3 vs . 3.2 ± 1.0, P = 0.001), and pain prior to discharge (2.0 ± 0.6 vs . 1.4 ± 0.0, P = 0.002) were significantly improved in RSPC., Conclusion: RSPC is feasible, safe, and effective. The perioperative outcomes are better compared with Si-robotic single-site surgical systems., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2021, the Korean Surgical Society.)

Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high-performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase-transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase-catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high-value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

An efficient flow process for the selective hydroboration and oxidation of different alkenes using 9-borabicyclo(3.3.1)nonane (9-BBN) allows facile conversion in high productivity (1.4 g h -1 ) of amorpha-4,11-diene to the corresponding alcohol, which is an advanced intermediate in the synthesis of the antimalarial drug artemisinin. The in situ reaction of borane and 1,5-cyclooctadiene using a simple flow generator proved to be a cost efficient solution for the generation of 9-BBN., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Terpene synthases catalyse the first step in the conversion of prenyl diphosphates to terpenoids. They act as templates for their substrates to generate a reactive conformation, from which a Mg 2+ -dependent reaction creates a carbocation-PP i ion pair that undergoes a series of rearrangements and (de)protonations to give the final terpene product. This tight conformational control was exploited for the (R)-germacrene A synthase- and germacradien-4-ol synthase-catalysed formation of a medium-sized cyclic terpenoid ether from substrates containing nucleophilic functional groups. Farnesyl diphosphate analogues with a 10,11-epoxide or an allylic alcohol were efficiently converted to a 11-membered cyclic terpenoid ether that was characterised by HRMS and NMR spectroscopic analyses. Further experiments showed that other sesquiterpene synthases, including aristolochene synthase, δ-cadinene synthase and amorphadiene synthase, yielded this novel terpenoid from the same substrate analogues. This work illustrates the potential of terpene synthases for the efficient generation of structurally and functionally novel medium-sized terpene ethers., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sesquiterpene synthases catalyze the conversion of farnesyl diphosphate to more than 300 different hydrocarbon and alcohol natural products which often contain multiple fused rings and stereocenters. Recent work has taken advantage of the exquisite stereospecificity of these enzymes to synthesize complex novel sesquiterpenoids using nonnatural substrates. In this chapter, we describe the expression, purification, and use of one such synthase to convert a nonnatural substrate to a novel cyclic ether, thereby expanding the terpenome., (© 2018 Elsevier Inc. All rights reserved.)

Background: Garlic is widely used by patients for its blood pressure lowering effects. A meta-analysis published in 2008 concluded that garlic consumption lowers blood pressure in hypertensive and normotensive patients. Therefore, it is important to review the currently available evidence to determine whether garlic may also have a beneficial role in the reduction of cardiovascular events and mortality rates in patients with hypertension., Objectives: To determine whether the use of garlic as monotherapy, in hypertensive patients, lowers the risk of cardiovascular morbidity and mortality compared to placebo., Search Methods: A systematic search for trials was conducted in the Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE, EMBASE, AGRICOLA, AMED, and CINAHL up to November 2011. A hand search of reference lists of identified reviews was conducted. Experts in the area were also contacted to identify trials not found in the electronic search. Clinicaltrials.gov was searched for ongoing trials., Selection Criteria: Randomized, placebo-controlled trials of any garlic preparation versus placebo for the treatment of hypertension were included., Data Collection and Analysis: Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5., Main Results: The search identified two randomized controlled trials for inclusion. One trial included 47 hypertensive patients and showed that garlic significantly reduces mean supine systolic blood pressure by 12 mmHg (95% CI 0.56 to 23.44 mmHg, p=0.04) and mean supine diastolic blood pressure by 9 mmHg (95% CI 2.49 to 15.51 mmHg, p=0.007) versus placebo. The authors state that garlic was "free from side effects" and that no serious side effects were reported. There were 3 cases "where a slight smell of garlic was noted."The second trial could not be meta-analysed as they did not report the number of people randomized to each treatment group. They did report that 200 mg of garlic powder given three times daily, in addition to hydrochlorothiazide-triamterene baseline therapy, produced a mean reduction of systolic blood pressure by 10-11 mmHg and of diastolic blood pressure by 6-8 mmHg versus placebo.Neither trial reported clinical outcomes and insufficient data was provided on adverse events., Authors' Conclusions: There is insufficient evidence to determine if garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of mortality and cardiovascular morbidity in patients diagnosed with hypertension. There is also insufficient evidence to determine the difference in withdrawals due to adverse events between patients treated with garlic or placebo.Based on 2 trials in 87 hypertensive patients, it appears that garlic reduces mean supine systolic and diastolic blood pressure by approximately 10-12 mmHg and 6-9 mmHg, respectively, over and above the effect of placebo but the confidence intervals for these effect estimates are not precise and this difference in blood pressure reduction falls within the known variability in blood pressure measurements. This makes it difficult to determine the true impact of garlic on lowering blood pressure.

Microsomal triglyceride transfer protein (Mtp) inhibitors represent a novel therapeutic approach to lower circulating LDL cholesterol, although therapeutic development has been hindered by the observed increase in hepatic triglycerides and liver steatosis following treatment. Here, we used small interfering RNAs (siRNA) targeting Mtp to achieve target-specific silencing to study this phenomenon and to determine to what extent liver steatosis is induced by changes in Mtp expression. We observed that Mtp silencing led to a decrease in many genes involved in hepatic triglyceride synthesis. Given the role of diacylglycerol O-acyltransferase 2 (Dgat2) in regulating hepatic triglyceride synthesis, we then evaluated whether target-specific silencing of both Dgat2 and Mtp were sufficient to attenuate Mtp silencing-induced liver steatosis. We showed that the simultaneous inhibition of Dgat2 and Mtp led to a decrease in plasma cholesterol and a reduction in the accumulation of hepatic triglycerides caused by the inhibition of Mtp. Collectively, these findings provide a proof-of-principle for a triglyceride synthesis/Mtp inhibitor combination and represent a potentially novel approach for therapeutic development in which targeting multiple pathways can achieve the desired response.

Thiopental is a barbiturate used in traumatic brain injuries (TBIs) to reduce intracranial pressure (ICP) and to manage cerebral ischemia. As thiopental follows Michaelis-Menten kinetics, therapeutic drug monitoring (TDM) has been used in practice to improve efficacy and reduce adverse effects. However, its role is still debatable, and TDM is not widely practiced. Current evidence suggests that thiopental therapy may improve mortality and functional outcome in a subpopulation of patients with severe TBI with elevated ICP refractory to conventional medical therapy. Several analytical methods are available to quantify thiopental concentrations. This review uses a previously published 9-step decision-making algorithm to determine whether TDM of thiopental in TBI is warranted. There seems to be poor correlation between thiopental concentration and pharmacological response in terms of neurological response, ICP, electroencephalography, and drug toxicity. There is no established therapeutic range for thiopental continuous infusion due to a wide range of plasma concentrations corresponding to efficacy (25-50 mg/L) and toxicity (30-70 mg/L) and the resulting overlap between the 2. Thiopental exhibits intrapatient and interpatient variability due to age, obesity, renal and hepatic dysfunction, Michaelis-Menten kinetics, and hepatic enzyme autoinduction. Available evidence suggests that TDM of thiopental continuous infusion is not beneficial in improving efficacy or avoiding toxicity. There are however 2 possible scenarios in which TDM may provide additional information to sound clinical judgment. The first is providing patient-specific plasma target concentration to guide titration of therapy. The second scenario is differentiating between brain death and barbiturate-induced coma.

Sucrose phosphate synthase (SPS) catalyzes the transfer of a glycosyl group from an activated donor sugar, such as uridine diphosphate glucose (UDP-Glc), to a saccharide acceptor D-fructose 6-phosphate (F6P), resulting in the formation of UDP and D-sucrose-6'-phosphate (S6P). This is a central regulatory process in the production of sucrose in plants, cyanobacteria, and proteobacteria. Here, we report the crystal structure of SPS from the nonphotosynthetic bacterium Halothermothrix orenii and its complexes with the substrate F6P and the product S6P. SPS has two distinct Rossmann-fold domains with a large substrate binding cleft at the interdomain interface. Structures of two complexes show that both the substrate F6P and the product S6P bind to the A-domain of SPS. Based on comparative analysis of the SPS structure with other related enzymes, the donor substrate, nucleotide diphosphate glucose, binds to the B-domain of SPS. Furthermore, we propose a mechanism of catalysis by H. orenii SPS. Our findings indicate that SPS from H. orenii may represent a valid model for the catalytic domain of plant SPSs and thus may provide useful insight into the reaction mechanism of the plant enzyme.

The hormone leptin plays a crucial role in maintenance of body weight and glucose homeostasis. This occurs through central and peripheral pathways, including regulation of insulin secretion by pancreatic beta cells. To study this further in mice, we disrupted the signaling domain of the leptin receptor gene in beta cells and hypothalamus. These mice develop obesity, fasting hyperinsulinemia, impaired glucose-stimulated insulin release, and glucose intolerance, similar to leptin receptor null mice. However, whereas complete loss of leptin function causes increased food intake, this tissue-specific attenuation of leptin signaling does not alter food intake or satiety responses to leptin. Moreover, unlike other obese models, these mice have reduced fasting blood glucose. These results indicate that leptin regulation of glucose homeostasis extends beyond insulin sensitivity to influence beta cell function, independent of pathways controlling food intake. These data suggest that defects in this adipoinsular axis could contribute to diabetes associated with obesity.

This is the first report of the crystallization of a sucrose phosphate synthase (SPS; EC 2.4.1.14). It also constitutes the first study of a sucrose phosphate synthase from a non-photosynthetic thermohalophilic anaerobic bacterium, Halothermothrix orenii. The purified recombinant spsA protein has been crystallized in the monoclinic space group C2, with unit-cell parameters a = 154.2, b = 47.9, c = 72.3 A, beta = 103.16 degrees, using the hanging-drop vapour-diffusion method. The crystal diffracts X-rays to a resolution limit of 3.01 A. Heavy-metal and halide-soaking trials are currently in progress to solve the structure.