Control Levels Research Articles

SUMOylation of cardiac myosin binding protein-C reduces its phosphorylation and results in impaired relaxation following treatment with isoprenaline

Systolic and diastolic functions are coordinated in the heart by myofilament proteins that influence force of contraction and calcium sensitivity. Fine control of these processes is afforded by a variety of post-translation modifications that occur on specific proteins at different times during each heartbeat. Cardiac myosin binding protein-C is a sarcomeric accessory protein whose function is to interact transiently with actin, tropomyosin and myosin. Previously many different types of post-translational modification have been shown to influence the action of myosin binding protein-C and we present the first report that the protein can be modified covalently by the small ubiquitin like modifier protein tag. Analysis by mass spectrometry suggests that there are multiple modification sites on myosin binding protein-C for this tag and single point mutations did not serve to abolish the covalent addition of the small ubiquitin like modifier protein. Functionally, our data from both model human embryonic kidney cells and transfected neonatal cardiac myocytes suggests that the modification reduces phosphorylation of the filament protein on serine 282. In cardiac myocytes, the hypo-phosphorylation coincided with a significantly slower relaxation response following isoprenaline induced contraction. We hypothesise that this novel modification of myosin binding protein-C represents a new level of control that acts to alter the relaxation kinetics of cardiac myocytes.

Situational control and strategic choices during supply chain disruptions: case studies of SME exporters

PurposeMotivated by the severe impact of global supply chain disruptions and the lack of understanding of supply chain resilience from an SME exporter perspective in the international marketing literature, this paper sets out to explore how SME exporters achieve resilience through strategic choices related to sourcing and manufacturing during global disruptions.Design/methodology/approachThe study adopts a qualitative, multiple-case-studies approach to identify the key strategic drivers and contextual factors influencing SME exporters’ supply chain resilience. Our study adopted an SME exporter perspective and featured an unprecedented global supply chain disruption context. New Zealand (NZ) was chosen as the key home country context for the participants of this study. Five NZ SME exporters were selected for our case studies.FindingsThis study redefines buffering, bridging and a mixed strategy for an SME exporter facing global supply chain disruptions. SME exporters with high situational control are likely to pursue a buffering strategy that reduces their resource dependence on foreign suppliers and their reliance on information support from these suppliers. In contrast, when the firm perceives little control over the supply chain, it will decide upon a bridging strategy that aims to build solid relationships with supply chain partners. Exporters opt for a mixed strategy when they do not see themselves clearly in high or low situational control.Research limitations/implicationsAs global disruptions arise and evolve, supply chain uncertainty and exporters’ sense of situational control manifest differently across industries, product lines, markets and sourcing countries. It is essential to understand that firms can choose a mixed strategy based on these supply chain conditions. While our study was fortuitously timed, conducting multi-country studies could provide more comparative insights that transcend national borders. Additionally, our study did not examine organizational and capability-based factors. Future research may benefit from exploring how an SME exporter develops strategic capabilities to achieve resilience over its lifetime.Practical implicationsBusinesses see survival as the most pivotal concern during a global supply chain disruption. Many companies have had to make on-the-spot decisions about whether they should shift or redesign their supply chains in the middle of a global disruption. There is no “best strategy” for an SME exporter to take. Rather, managers should make strategic decisions based on how much control or influence they have over a particular part of their supply chain. The level of control is determined by the SME exporter’s overall resource dependencies and information needs in particular parts of their supply chain.Originality/valueWe adopt resource dependence theory and information processing theory to guide our study and place exporters' situational control in the centre of drivers to firms' strategic choices during global disruptions. We make a novel attempt to incorporate the contextual conditions of the COVID-19 pandemic into the theorization of supply chain resilience. We make managerial recommendations to help SME exporters navigate global supply chain disruption challenges.

Unexpected sustained soil carbon flux in response to simultaneous warming and nitrogen enrichment compared with single factors alone.

Recent observations document that long-term soil warming in a temperate deciduous forest leads to significant soil carbon loss, whereas chronic soil nitrogen enrichment leads to significant soil carbon gain. Most global change experiments like these are single factor, investigating the impacts of one stressor in isolation of others. Because warming and ecosystem nitrogen enrichment are happening concurrently in many parts of the world, we designed a field experiment to test how these two factors, alone and in combination, impact soil carbon cycling. Here, we show that long-term continuous soil warming or nitrogen enrichment when applied alone followed the predicted response, with warming resulting in significant soil carbon loss and nitrogen fertilization tending towards soil carbon gain. The combination treatment showed an unanticipated response, whereby soil respiratory carbon loss was significantly higher than either single factor alone, but without a concomitant decline in soil carbon storage. Observations suggest that when soils are exposed to both factors simultaneously, plant carbon inputs to the soil are enhanced, counterbalancing soil carbon loss and helping maintain soil carbon stocks near control levels. This has implications for both atmospheric CO2 emissions and soil fertility and shows that coupling two important global change drivers results in a distinctive response that was not predicted by the behaviour of the single factors in isolation.

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Associations between hypertensive snowbirds' length of migratory stay and blood pressure control

Objective: To explore the relationship between the hypertensive snowbirds' length of migratory stay and their blood pressure control and blood pressure levels. Methods: This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds' length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines. Results: A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants' self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds' length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure (β=-1.19, P=0.003). Conclusions: Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Peak expiratory flow rate monitoring can predict asthma exacerbation better as compared to monitoring by symptoms, prospective cohort study

Background: Global initiative for asthma (GINA) guidelines suggest to use peak expiratory flow rate (PEFR) monitoring to assess response to treatment, to identify triggers for exacerbation and to have a baseline value for action plan (especially for the poor perceivers). In comparison to adults, there are less evidence in support of the routine use of PEFR recording for the diagnosis and monitoring level of control of asthma in children. This study was conducted with objective to assess the effect of PEFR monitoring on numbers of exacerbations in comparison to monitoring by symptoms in asthma. Methods: This was a prospective cohort study done for a in department of pediatrics and respiratory medicine, of a tertiary care hospital, North India. Prior to recruitment ethical approval and informed consent/assent was taken. Study subjects were children with partial and uncontrolled asthma aged 5-12 years of age. Patients were divided into two groups on their first visit by using random allocation number. In group “A” monitoring was done with symptoms only, while in group “B” monitoring was done by symptoms and PEFR. Number of exacerbations during study period was noted. At baseline and follow up, CACT score was calculated. Spirometry was done at the end of 3 months. Results: Group B had statistically significant lesser exacerbation during study period as compared to group A (OR=0.23; 95% CI=0.06-0.81; p=0.020). Conclusions: PEFR based monitoring can be used as a potential tool for aborting or decreasing the severity of episodes of exacerbations of asthma especially in resource limited areas.

Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection.

Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers contributed by uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of CSF proteins in HIV-associated dementia (HAD) and neurosymptomatic CSF escape (NSE). These reveal a complex but coherent picture of CSF protein changes with highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of systemic HIV-1 progression that included two common patterns, designated as lymphoid and myeloid patterns, related to principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will supplement this report to provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, advancing the mechanistic understanding of HIV-1-related CNS pathobiology.

It takes two peroxisome proliferator-activated receptors (PPAR-β/δ and PPAR-γ) to tango idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung epithelial phenotypes, fibroblast activation, and increased extracellular matrix deposition. Transforming growth factor-beta (TGF-β)1-induced Smad signaling and downregulation of peroxisomal genes are involved in the pathogenesis and can be inhibited by peroxisome proliferator-activated receptor (PPAR)-α activation. However, the three PPARs, that is PPAR-α, PPAR-β/δ, and PPAR-γ, are known to interact in a complex crosstalk.MethodsTo mimic the pathogenesis of lung fibrosis, primary lung fibroblasts from control and IPF patients with comparable levels of all three PPARs were treated with TGF-β1 for 24 h, followed by the addition of PPAR ligands either alone or in combination for another 24 h. Fibrosis markers (intra- and extracellular collagen levels, expression and activity of matrix metalloproteinases) and peroxisomal biogenesis and metabolism (gene expression of peroxisomal biogenesis and matrix proteins, protein levels of PEX13 and catalase, targeted and untargeted lipidomic profiles) were analyzed after TGF-β1 treatment and the effects of the PPAR ligands were investigated.ResultsTGF-β1 induced the expected phenotype; e.g. it increased the intra- and extracellular collagen levels and decreased peroxisomal biogenesis and metabolism. Agonists of different PPARs reversed TGF-β1-induced fibrosis even when given 24 h after TGF-β1. The effects included the reversals of (1) the increase in collagen production by repressing COL1A2 promoter activity (through PPAR-β/δ activation); (2) the reduced activity of matrix metalloproteinases (through PPAR-β/δ activation); (3) the decrease in peroxisomal biogenesis and lipid metabolism (through PPAR-γ activation); and (4) the decrease in catalase protein levels in control (through PPAR-γ activation) and IPF (through a combined activation of PPAR-β/δ and PPAR-γ) fibroblasts. Further experiments to explore the role of catalase showed that an overexpression of catalase protein reduced collagen production. Additionally, the beneficial effect of PPAR-γ but not of PPAR-β/δ activation on collagen synthesis depended on catalase activity and was thus redox-sensitive.ConclusionOur data provide evidence that IPF patients may benefit from a combined activation of PPAR-β/δ and PPAR-γ.

Разработка опросника «Шкала финансовой автономности личности» и его психометрическая проверка на группе предпенсионеров

Relevance: the issues of studying subjective qualities of the pre-retiree’s personality, including their financial autonomy, are of particular relevance due to economic instability and uncertainty. The present article is devoted to the problem of measuring financial autonomy in the situation of retirement planning which is one of the indicators of economic and psychological maturity of a person. The purpose of the work is to conduct a psychometric test of the original author’s questionnaire “Individual’s Financial Autonomy Scale” (T. V. Drobysheva, I. V. Larionov, S. V. Tarasov). Hypothesis: an individual’s financial autonomy scale has a one-dimensional structure and is associated with internal locus control and autonomy interpreted as the individual’s independence. Participants: 215 pre-retirees (from 45 to 63 years old) living in different regions of the Russian Federation including 108 women and 107 men, 49% are working and 51% are unemployed. Techniques (tools): subscale “Autonomy” of K. Ryff’s Scale of Psychological Well-Being (adapted by T. D. Shevelenkova, T. P. Fesenko), the Subjective Control Level Questionnaire (compiled by E. F. Bazhin, E. A. Golynkina, L. M. Etkind); the results were processed with the help of the software packages IBM SPSS.22.0, IBM AMOS 19.0, Jamovi 2.4.11. Results: the initial standardization of the questionnaire has been carried out. A check for normality and internal consistency has been performed. The study has evaluated the factor structure, discriminatory power and convergent validity of the questionnaire. The results show that the Individual’s Financial Autonomy Scale has a one-factor structure and is characterized by high indicators of psychometric reliability. Main conclusions: the Individual’s Financial Autonomy Scale is a reliable tool that measures financial autonomy as the ability of a person to manage their finances regardless of the opinions of others, to make appropriate decisions and to take responsibility for them, as well as to monitor their financial state. The study describes differences in the degree of autonomy in different groups of pre-retirees. The practical significance of the research is determined by the necessity to provide targeted assistance to pre-retirees in planning their retirement on the basis of the financial autonomy indicators measured with the scale.

Extracellular DNA from the blood plasma of patients with schizophrenia stimulates the TLR9-NF-kB signaling pathway in cultured human lymphocytes

Schizophrenia is a mental illness of complex etiology. Recently, there has been increased interest in the role of the immune system in the pathophysiology of mental disorders. The concept of neuroinflammation in neurodevelopmental disorders is gaining widespread interest, including the role of Toll-like receptors.Schizophrenia is associated with an increase in the concentration of cfDNA in human blood, and the composition of cfDNA fragments changes significantly compared to cellular DNA: GC-rich fragments of the ribosomal repeat accumulate and base oxidation occurs. Similar changes, but less pronounced, also occur for cfDNA from healthy donors.To confirm the hypothesis about the possible participation of cfDNA in the inflammation induction, we studied the effect of cfDNA samples on cultured mononuclear cells.Unlike cellular DNA, cfDNA(SZ) and cfDNA(K) stimulate transcription of the TLR9 gene in mononuclear cells. After 1 hour the amount of TLR9 RNA increases by 2.9 and 3.3 times compared to the control. After 24 hours, the TLR9 RNA level decreases slightly, but is still 2-3 times higher than the control level. After 1 hour, TLR9 protein increases by 1.5 and 1.7 times, respectively, and further increased after 24h of culture.An increase TLR9 protein expression correlates with an increase of the transcription factor NF-kB in lymphocytes and is accompanied by an increase in proinflammatory cytokine IL8 RNA, the transcription of IL8 is controlled by the NF-kB factor.Thus, cfDNA(SZ) and cfDNA(K) stimulate the TLR9-NF-kB-proinflammatory cytokine signaling pathway in lymphocytes. The effect of cfDNA also depends on the concentration of these fragments in the extracellular environment. Since the concentrations of cfDNA in the blood of patients with schizophrenia are significantly increased compared to healthy donors, we should expect a much higher level of activation of the TLR9-NF-kB signaling pathway in the body cells of sick people.Samples of cfDNA from patients with schizophrenia have a pronounced biological effect on cells of the immune system, stimulating the synthesis of pro-inflammatory cytokines by activating the TLR9-NF-kB-proinflammatory cytokines signaling pathway. High levels of cfDNA in blood plasma may be one of the reasons for the induction and maintenance of low-level inflammation in schizophrenia.

MiRNAs in Extracellular Vesicles as Biomarkers in Plasma of Papillary Thyroid Cancer Patients: A Proof-of-Concept Study.

The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized. The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC. Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

Biochemical and Epigenetic Regulation of Glutamate Metabolism in Maize (Zea mays L.) Leaves under Salt Stress.

The effect of salt stress (150 mM NaCl) on the expression of genes, methylation of their promoters, and enzymatic activity of glutamate dehydrogenase (GDH), glutamate decarboxylase (GAD), and the 2-oxoglutarate (2-OG)-dehydrogenase (2-OGDH) complex was studied in maize (Zea mays L.). GDH activity increased continuously under salt stress, being 3-fold higher after 24 h. This was accompanied by the appearance of a second isoform with lower electrophoretic mobility. The expression of the Gdh1 gene strongly increased after 6-12 h of incubation, which corresponded to the demethylation of its promoter, while Gdh2 gene expression slightly increased after 2-6 h and then decreased. GAD activity gradually increased in the first 12 h, and then returned to the control level. This corresponded to the increase of Gad expression and its demethylation. Salt stress led to a 2-fold increase in the activity of 2-OGDH during the first 6 h of NaCl treatment, then the activity returned to the control level. Expression of the genes Ogdh1 and Ogdh3 peaked after 1-2 h of incubation. After 6-8 h with NaCl, the expression of these genes declined below the control levels, which correlated with the higher methylation of their promoters. We conclude that salt stress causes a redirection of the 2-OG flux to the γ-aminobutyric acid shunt via its amination to glutamate, by altering the expression of the Gdh1 and Gdh2 genes, which likely promotes the assembly of the native GDH molecule having a different subunit composition and greater affinity for 2-OG.

Enhancing DC microgrids cluster performance with distributed event-triggered consensus protocols

Microgrid (MG) clusters offer solutions to the challenges faced by individual MGs in extreme conditions but require precise coordination to manage generation-load imbalances effectively. This paper presents a hierarchical control strategy that combines time-based and event-based consensus protocols (ETC) in the overarching control layer. Traditional time-based protocols require constant sampling, leading to unnecessary communication and computational burdens. To address this, we introduce a mixed time-state dependent distributed event-triggered consensus protocol (MDETC), which reduces communication needs while maintaining MG performance. A set-time consensus algorithm is used at the secondary control level to synchronize currents and voltages quickly. Additionally, the integration of Particle Swarm Optimization (PSO) in primary control ensures efficient current distribution and voltage regulation among neighboring MGs. The study also explores automatic reconfiguration within the cluster to support Plug-N-Play functionality, ensuring seamless MG operation. The effectiveness of this control approach is demonstrated through MATLAB simulations of a four-DC MG cluster, showing improved efficiency in reducing triggering instances and achieving faster current and voltage stabilization under various conditions.

Enhancing prediction of elemental composition through machine learning decision tree models for biomass gasification optimization

Abstract The worldwide transition to cleaner, sustainable energy sources, prompted by population growth and industrialization, responds to uncertain fossil fuel prices and environmental concerns, highlighting the substantial benefits of renewable energy in reducing greenhouse gas emissions and addressing climate change. Derived from non-fossilized organic materials, biomass emerges as a significant and sustainable contributor to renewable energy. Its diverse nature is complemented by a range of conversion technologies, encompassing combustion, pyrolysis, gasification, and liquefaction, providing versatile avenues for biomass energy transformation. Gasification, the transformative process of converting organic matter into combustible gases under controlled oxygen levels, is accomplished through direct oxygen supply or pyrolysis. This method yields a dependable gaseous fuel versatile for heating, industrial processes, power generation, and liquid fuel production. Machine learning employs advanced statistical techniques for modeling across diverse industries, showcasing particular efficacy in optimizing thermochemical processes by precisely identifying the optimal operating conditions required for achieving desired product properties. These models utilize proximate biomass data to predict the elemental compositions of N2 and H2. Assessment of both single and two hybrid models indicated that the introduced optimizers significantly enhanced the estimation of N2 and H2 when combined with Decision Tree (DT), with Decision Tree Coupled with Artificial Hummingbird Algorithm (DTAH) proving particularly effective. Notably, DTAH demonstrated outstanding performance with remarkable R 2 values of 0.990 for N2 and 0.992 for H2. Additionally, the minimal Root Mean Square Error (RMSE) values of 1.291 and 1.550 for N2 and H2 predictions respectively underscore the precision of DTAH, establishing it as a suitable choice for practical real-world applications.

Older adults’ experiences of being screened for fall risk in a clinical setting: a focus group study

Abstract Purpose There is a need for further research on older adults’ experiences of fall risk screening to improve health communication strategies. The purpose of this study was to describe and explore older adults’ experiences of being screened for risk of an injurious fall, using the first-time injurious falls (FIF) screening tool. Methods A qualitative study with five focus group interviews was carried out including 17 older adults (11 women and six men, with a mean age of 77.4 years) who were recruited from two primary healthcare rehabilitation clinics in Sweden. Data were analyzed using reflexive thematic analysis. Results The analysis generated one overarching theme, “Screening for fall risk promotes engagement by raising older adults’ awareness of their own abilities”, and four categories; “Screening may motivate to take action but can also create a false sense of security”, “Self-sufficiency is affected by the screening result and level of control over the environment”, “Easy-to-perform and helps to facilitate a discussion with the healthcare professional” and “Ideas of how FIF tool could be used in healthcare”. Conclusion Older adults considered screening for fall risk to be meaningful insofar as it raises awareness of their own abilities and motivates them to prevent falls. On the other hand, a low fall risk could create a false sense of security, and lack of control over environmental factors related to fall risk could negatively impact their sense of self-sufficiency. They emphasized the need to receive support from healthcare providers and to be involved in care decisions if the screening indicates a high fall risk.

Comparative Pharmacokinetics and Tissue Distribution of Hexahydrocurcumin Following Intraperitoneal vs Oral Administration in Mice Using LC-MS/MS.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine hexahydrocurcumin (HHC) levels in mouse plasma, brain, liver, and kidneys using a negative ion mode electrospray ionization (ESI) source. Demonstrating a lower limit of quantification (LLOQ) of 5 ng/mL, the method showed excellent linearity across a concentration range of 5-500 ng/mL in all tested matrices. Precision evaluations reported a coefficient of variation (CV%) of less than 13.19% for both intraday and interday measurements, while accuracy ranged from 95.13 to 105.07% across all quality control levels. HHC extraction recovery was consistently observed between 70.18 and 93.28%, with a CV% deviation of less than 15%. In the pharmacokinetic evaluation of HHC in mice following a single intraperitoneal (IP) or oral administration, a noncompartment analysis was utilized. After IP administration (40 mg/kg), the C max value was 47.90 times higher than that achieved via oral administration. Peak plasma concentrations were observed approximately 5 min post-IP and 15 min post-oral dosing. The observed half-lives after these administrations were approximately 1.52 and 2.17 h for IP and oral routes, respectively. Oral administration revealed a relative bioavailability of only 12.28% compared with the IP route. Furthermore, following IP administration, the half-life values in brain, liver, and kidney were not significantly different but more than the half-life value found in plasma. The liver and kidney exhibited the highest concentrations of HHC, while the brain showed the least, suggesting that the hydrophobic nature of HHC impedes its passage through the blood-brain barrier. This study is the first to provide detailed insights into the pharmacokinetics and tissue distribution characteristics of HHC following oral and IP administration in mice, setting the stage for further focus on HHC as a potential new drug candidate.

Error analysis model-driven workflow for self-calibration stitching testing of X-ray flat surfaces

Self-calibration stitching test is widely utilized for testing X-ray flat surfaces. Various factors, including environment disturbances, motion errors, misalignments, overlapping ratios, and sub-aperture sizes can affect the accuracy. Previous studies have shown that motion errors can introduce slope errors in the test surface, and higher overlapping ratios can increase the test error. However, these error analyses have not been comprehensive or quantitatively sufficient for practical applications. For X-ray flat surfaces with specific accuracy requirements, the necessary control levels for error sources and the optimal test parameters remain unclear. To this end, an error analysis model-driven workflow for self-calibration stitching testing of X-ray flat surfaces is proposed. This model allows for the systematic evaluation of how different error sources and test parameters affect test accuracy. Further, it can guide the determination of the control levels of error sources and test parameters, moving beyond the reliance on empirical experience as seen in previous studies. A flat X-ray mirror with clear aperture of 250 mm × 30 mm and 0.2 nm (50 nrad) RMS accuracy requirement was utilized to demonstrate the procedures of the workflow. Verification experiments demonstrated that this workflow can serve as a standard model for evaluating test accuracy and guiding test procedures to achieve the desired accuracy in self-calibration stitching of X-ray flat mirrors.

Different mulch films, consistent results: soil fauna responses to microplastic

Agricultural activities contribute to plastic pollution, with unintentional introduction and intentional use of plastic mulch films leading to the accumulation of microplastic particles in soils. The lack of removal techniques and scarce information on the effects on soil organisms, especially for biodegradable mulch films, necessitate an assessment of potential effects. This study aimed to elucidate the effects of mulch film microplastic on soil fauna by investigating reproduction output and subcellular responses before and after recovery from exposure. Two common soil organisms, Folsomia candida and Eisenia fetida, were exposed to petroleum-based polyethylene (PE) and biodegradable polylactic acid/polybutylene adipate terephthalate (PLA/PBAT) microplastic for 28 days, according to OECD guidelines 232 and 222, respectively. Juvenile numbers revealed no polymer- or concentration-dependent effects on E. fetida and F. candida reproduction after exposure to up to 5 and 10 g/kgdw soil, respectively. To provide a more sensitive and early indication of sublethal effects, subcellular responses in E. fetida were analyzed. Glutathione S-transferase (GST) activity increased with rising microplastic concentration; however, catalase (CAT), acetylcholine esterase (AChE) activity, and reactive oxygen species (ROS) did not differ from control levels. Further, the more environmentally relevant PE polymer was chosen for in-depth assessment of subcellular response after 28-day microplastic exposure and subsequent 28 days in uncontaminated soil with E. fetida. No significant differences in biomarker activity and stress levels were observed. We conclude that mulch film–derived microplastic did not adversely affect earthworm and collembolan species in this scenario, except for a slight induction in the detoxification enzyme glutathione S-transferase.

Advanced CMOS manufacturing of superconducting qubits on 300 mm wafers

The development of superconducting qubit technology has shown great potential for the construction of practical quantum computers1,2. As the complexity of quantum processors continues to grow, the need for stringent fabrication tolerances becomes increasingly critical3. Utilizing advanced industrial fabrication processes could facilitate the necessary level of fabrication control to support the continued scaling of quantum processors. However, at present, these industrial processes are not optimized to produce high-coherence devices, nor are they a priori compatible with the approaches commonly used to make superconducting qubits. Here we demonstrate superconducting transmon qubits manufactured in a 300 mm complementary metal–oxide–semiconductor (CMOS) pilot line using industrial fabrication methods, with resulting relaxation and coherence times exceeding 100 μs. We show across-wafer, large-scale statistics of coherence, yield, variability and ageing that confirm the validity of our approach. The presented industry-scale fabrication process, which uses only optical lithography and reactive-ion etching, has a performance and yield in line with conventional laboratory-style techniques utilizing metal lift-off, angled evaporation and electron-beam writing4. Moreover, it offers the potential for further upscaling through three-dimensional integration5 and more process optimization. This result marks the advent of an alternative and new, large-scale, truly CMOS-compatible fabrication method for superconducting quantum computing processors.

Особенности взаимосвязи регуляции кардиоритма и компонентов внутренней картины болезни у студентов

&lt;p&gt;The work is aimed at identifying the features of the mechanisms of regulation of cardiac rhythm, which determine adaptive behavior in situations of health disorders. Materials from two empirical studies conducted on a sample of 1&lt;sup&gt;st&lt;/sup&gt; to 4&lt;sup&gt;th&lt;/sup&gt; year students at Yelets University are presented. The study 1 (N=160) involved respondents aged 17 to 23 years of both sexes, of whom 37.5% had various health problems. In study 2 (N=60), students (average age 21&amp;plusmn;2.3 years), of which 50% belong to the category of chronically ill, 50% had periodic health problems. Study 2 included five stages, in which four levels of the internal picture of the disease (IPD) were diagnosed and cardiac rhythm measurements were performed at rest and against the background of existing disease memories. The following methods were used: SF-36 Health Status Survey, Health, Activity, and Mood questionnaire, SCL-90-R, &amp;ldquo;Coping behavior in stressful situations&amp;rdquo;, &amp;ldquo;Level of subjective control&amp;rdquo;, TATD method. The fixation of the heart rate variability was carried out using the hardware and software complex OMEGA-M. The results obtained allow us to say that there is a correlation between the individual components of IPD and the parameters of regulation of heart rate variability. The optimal state of the body's homeostatic systems, which ensure successful adaptation, is characterized by the activity of the parasympathetic department of autonomic nervous system in the process of cardioregulation.&lt;/p&gt;