Effects of background doping, interdiffusion and layer thickness fluctuation on the transport characteristics of THz quantum cascade lasers.

In this work, we investigate the effects of n and p-type background doping, interface composition diffusion (interdiffusion) of the barrier material and layer thickness variation during molecular beam epitaxy (MBE) growth on transport characteristics of terahertz-frequency quantum cascade lasers (THz QCLs). We analysed four exemplary structures: a bound-to-continuum design, hybrid design, LO-phonon design and a two-well high-temperature performance LO-phonon design. The exemplary bound-to-continuum design has shown to be the most sensitive to the background doping as it stops lasing for concentrations around 1.0 · 10 15 - 2.0 · 10 15 cm - 3 . The LO-phonon design is the most sensitive to growth fluctuations during MBE and this is critical for novel LO-phonon structures optimised for high-temperature performance. We predict that interdiffusion mostly affects current density for designs with narrow barrier layers and higher Al composition. We show that layer thickness variation leads to significant changes in material gain and current density, and in some cases to the growth of nonfunctional devices. These effects serve as a beacon of fundamental calibration steps required for successful realisation of THz QCLs.

Resonant Tunnelling and Intersubband Optical Properties of ZnO/ZnMgO Semiconductor Heterostructures: Impact of Doping and Layer Structure Variation.

ZnO-based heterostructures are up-and-coming candidates for terahertz (THz) optoelectronic devices, largely owing to their innate material attributes. The significant ZnO LO-phonon energy plays a pivotal role in mitigating thermally induced LO-phonon scattering, potentially significantly elevating the temperature performance of quantum cascade lasers (QCLs). In this work, we calculate the electronic structure and absorption of ZnO/ZnMgO multiple semiconductor quantum wells (MQWs) and the current density-voltage characteristics of nonpolar m-plane ZnO/ZnMgO double-barrier resonant tunnelling diodes (RTDs). Both MQWs and RTDs are considered here as two building blocks of a QCL. We show how the doping, Mg percentage and layer thickness affect the absorption of MQWs at room temperature. We confirm that in the high doping concentrations regime, a full quantum treatment that includes the depolarisation shift effect must be considered, as it shifts mid-infrared absorption peak energy for several tens of meV. Furthermore, we also focus on the performance of RTDs for various parameter changes and conclude that, to maximise the peak-to-valley ratio (PVR), the optimal doping density of the analysed ZnO/Zn88Mg12O double-barrier RTD should be approximately 1018 cm-3, whilst the optimal barrier thickness should be 1.3 nm, with a Mg mole fraction of ~9%.

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats.

Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simulate low-dose Pb exposure in an animal model with the aim of assessing oxidative status and essential element levels as the main mechanism of Pb toxicity in the liver and kidneys. Furthermore, dose-response modelling was performed in order to determine the benchmark dose (BMD). Forty-two male Wistar rats were divided into seven groups: one control group, and six groups treated for 28 days with 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg b.w./day, respectively. Oxidative status parameters (superoxide dismutase activity (SOD), superoxide anion radical (O2-), malondialdehyde (MDA), total sulfhydryl groups (SHG), and advanced oxidation protein products (AOPP)) and Pb, copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels were measured. Lowering Cu levels (BMD: 2.7 ng/kg b.w./day), raising AOPP levels (BMD: 0.25 µg/kg b.w./day) in the liver, and inhibiting SOD (BMD: 1.3 ng/kg b.w./day) in the kidneys appear to be the main mechanisms of Pb toxicity. The lowest BMD was derived for a decrease in Cu levels in liver, indicating that this effect is the most sensitive.

Diabetic cardiomyopathy: The role of microRNAs and long non-coding RNAs.

Diabetes mellitus (DM) is on the rise, necessitating the development of novel therapeutic and preventive strategies to mitigate the disease's debilitating effects. Diabetic cardiomyopathy (DCMP) is among the leading causes of morbidity and mortality in diabetic patients globally. DCMP manifests as cardiomyocyte hypertrophy, apoptosis, and myocardial interstitial fibrosis before progressing to heart failure. Evidence suggests that non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), regulate diabetic cardiomyopathy-related processes such as insulin resistance, cardiomyocyte apoptosis and inflammation, emphasizing their heart-protective effects. This paper reviewed the literature data from animal and human studies on the non-trivial roles of miRNAs and lncRNAs in the context of DCMP in diabetes and demonstrated their future potential in DCMP treatment in diabetic patients.

New insights on the cardiovascular effects of IGF-1.

Introduction: Cardiovascular (CV) disorders are steadily increasing, making them the world's most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV health. Methods: We searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years. Results: IGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy. Discussion: We anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs.

RADON IN DRINKING WATER FROM ALTERNATIVE SOURCES OF WATER SUPPLY IN THE NORTH OF KOSOVO.

In this study, the results of research on radon activity concentrations in natural mineral waters, traditionally used for drinking but also for other needs, in rural and urban households in northern Kosovo are presented. Radon activity concentration in water was measured by the alpha spectrometric method with a RAD7 device. Radon activity concentrations in the 24 waters studied ranged from 1.6 ± 0.5 to 46.3 ± 6.3 Bq l-1, with an average activity concentration of 12.4 ± 2.0 Bq l-1, which was somewhat higher than the EPA recommended maximum activity concentration, but below the WHO recommended maximum. The contribution of radon activity concentrations in water was determined in relation to the total radon activity in air and enclosed space. The estimated annual effective doses of inhalation and ingestion radon from water were 109.4 ± 16.7 and 2.6 ± 0.4 µSv y-1, respectively.

Role of Chemerin in Cardiovascular Diseases.

(1) Background: Obesity is closely connected to the pathophysiology of cardiovascular diseases (CVDs). Excess fat accumulation is associated with metabolic malfunctions that disrupt cardiovascular homeostasis by activating inflammatory processes that recruit immune cells to the site of injury and reduce nitric oxide levels, resulting in increased blood pressure, endothelial cell migration, proliferation, and apoptosis. Adipose tissue produces adipokines, such as chemerin, that may alter immune responses, lipid metabolism, vascular homeostasis, and angiogenesis. (2) Methods: We performed PubMed and MEDLINE searches for articles with English abstracts published between 1997 (when the first report on chemerin identification was published) and 2022. The search retrieved original peer-reviewed articles analyzed in the context of the role of chemerin in CVDs, explicitly focusing on the most recent findings published in the past five years. (3) Results: This review summarizes up-to-date findings related to mechanisms of chemerin action, its role in the development and progression of CVDs, and novel strategies for developing chemerin-targeting therapeutic agents for treating CVDs. (4) Conclusions: Extensive evidence points to chemerin's role in vascular inflammation, angiogenesis, and blood pressure modulation, which opens up exciting perspectives for developing chemerin-targeting therapeutic agents for the treatment of CVDs.

Redox and biometal status in Wistar rats after subacute exposure to fluoride and selenium counter-effects.

This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals [copper (Cu), iron (Fe), and zinc (Zn)] in the blood, liver, kidney, brain, and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F-) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions ad libitum for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O2 .-) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O2 .- in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F- toxicity.

Fluoride subacute testicular toxicity in Wistar rats: Benchmark dose analysis for the redox parameters, essential elements and DNA damage.

Excessive fluoride (F-) levels in the environment could induce different pathological changes, including comorbidities in reproductive functions. Hence, the aim of the present in vivo study was to explore F- subacute toxicity mechanisms via Benchmark dose (BMD) methodology on rat's testicles. The experiment was conducted on thirty male Wistar rats for 28 days, divided into six groups (n = 5): 1) Control (tap water); 2) 10 mg/L F-; 3) 25 mg/L F-; 4) 50 mg/L F-; 5) 100 mg/L F-; 6) 150 mg/L F-. Testicles were dissected out and processed for the determination of F- tissue concentrations, redox status parameters, essential elements level, and DNA damage. PROASTweb 70.1 software was used for determination of external and internal dose-response relationship. The results confirmed a significant increase in superoxide anion (O2.-), total oxidative status (TOS), copper (Cu), zinc (Zn), iron (Fe), DNA damage levels, and decrease in superoxide dismutase activity (SOD1) and total thiol (SH) groups. The dose-dependent changes were confirmed for SOD1 activity and DNA damage. The most sensitive parameters were SOD1 activity and DNA damage with the lowest BMDLs 0.1 µg F-/kg b. w. Since human and animal populations are daily and frequently unconsciously exposed to F-, this dose-response study is valuable for further research regarding the F- health risk assessment.

Association Between Telomere Length and Cardiovascular Risk: Pharmacological Treatments Affecting Telomeres and Telomerase Activity.

Telomeres represent the ends of chromosomes, and they are composed of an extensive number of - TTAGGG nucleotide sequence repeats in humans. Telomeres prevent chromosome degradation, participate in stabilization, and regulate the DNA repair system. Inflammation and oxidative stress have been identified as important processes causing cardiovascular disease and accelerating telomere shortening rate. This review investigates the link between telomere length and pathological vascular conditions from experimental and human studies. Also, we discuss pharmacological treatments affecting telomeres and telomerase activity.

Identification of high radon dwellings, risk of exposure, and geogenic potential in the mining area of the "TREPCA" complex.

This study was performed to investigate radon levels in dwellings in the mining area near the town of Kosovska Mitrovica. The Passive radon technique based on the charcoal canister test kit conducted in summer and autumn 2019 showed unexpected results. The reference level of 300 Bq/m3 for indoor radon concentration was exceeded in 15 of 26 dwellings. Preliminary measurements of gamma dose rate in some dwellings built from local stone showed values from 0.30 to 0.45 µSv/h, while 75% of measurements in dwellings with stone foundations had radon above the reference level. The highest radon concentration (22 500 ± 220 Bq/m3 ) was measured in the cellar of one family house. The RAD7 device (Durridge Company, Inc.) was used to measure radon concentrations in water and nearby soil of some dwellings. Indoor radon concentration fluctuated significantly over two days; over a one-day time scale, radon varied from 2843 ± 217 Bq/m3 at midnight to 1449 ± 104 Bq/m3 in the morning at one site, and abruptly decreased from a maximum of 2146 ± 262 Bq/m3 in one day to a minimum of 21 Bq/m3 the next day at another site. The influence of geological substrate on radon exposure was discussed through the estimation of geogenic radon potential, which varies from low the high radon index despite to high permeability of soil.

Role of C-Reactive Protein in Diabetic Inflammation.

Even though type 2 diabetes mellitus (T2DM) represents a worldwide chronic health issue that affects about 462 million people, specific underlying determinants of insulin resistance (IR) and impaired insulin secretion are still unknown. There is growing evidence that chronic subclinical inflammation is a triggering factor in the origin of T2DM. Increased C-reactive protein (CRP) levels have been linked to excess body weight since adipocytes produce tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are pivotal factors for CRP stimulation. Furthermore, it is known that hepatocytes produce relatively low rates of CRP in physiological conditions compared to T2DM patients, in which elevated levels of inflammatory markers are reported, including CRP. CRP also participates in endothelial dysfunction, the production of vasodilators, and vascular remodeling, and increased CRP level is closely associated with vascular system pathology and metabolic syndrome. In addition, insulin-based therapies may alter CRP levels in T2DM. Therefore, determining and clarifying the underlying CRP mechanism of T2DM is imperative for novel preventive and diagnostic procedures. Overall, CRP is one of the possible targets for T2DM progression and understanding the connection between insulin and inflammation may be helpful in clinical treatment and prevention approaches.

Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis.

Linkage between bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA) co-exposure and type 2 diabetes mellitus (T2DM), as well as ability of multi-strained probiotic to reduce DEHP, DBP and BPA mixture-induced oxidative damage in rat pancreas were investigated. The Comparative Toxicogenomics Database, Cytoscape software and ToppGene Suite were used for data-mining. Animals were sorted into seven groups (n = 6): (1) Control group: corn oil, (2) P: probiotic: Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus plantarum LP 6595 + Lactobacillus plantarum HEAL9; (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day, and (6) MIX: 50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA; (7) MIX + P. Rats were sacrificed after 28 days of oral exposure. In silico investigation highlighted 44 DEHP, DBP and BPA mutual genes linked to the T2DM, while apoptosis and oxidative stress were highlighted as the main mechanisms of DEHP, DBP and BPA mixture-linked T2DM. In vivo experiment confirmed the presence of significant changes in redox status parameters (TOS, SOD and SH groups) only in the MIX group, indicating possible additive effects, while probiotic ameliorated mixture-induced redox status changes in rat pancreatic tissue.

Can the sensitivity of energetic materials be tuned by using hydrogen bonds? Another look at the role of hydrogen bonding in the design of high energetic compounds.

Strongly positive electrostatic potential in the central areas of molecules of energetic materials is one of the most important factors that determines the sensitivity of these molecules towards detonation. Quantum chemical and density functional theory calculations were used to reveal the influence of hydrogen bonding on the values of electrostatic potential above the central areas of molecules of three conventional explosives: 1,3,5-trinitrobenzene, 2,4,6-trinitrophenol, and 2,4,6-trinitrotoluene. Both the case when energetic molecules act as hydrogen atom donors and when they act as hydrogen atom acceptors were considered. Results of the calculations performed using the M06/cc-PVDZ level of theory showed that there are significant differences in the influence of hydrogen bonding on the electrostatic potential of energetic molecules acting as hydrogen atom donors and hydrogen atom acceptors. In the case when energetic molecules act as hydrogen acceptors, an increase of 10% in the strength of positive electrostatic potential was identified. In the case when energetic molecules act as hydrogen atom donors, a significant decrease (20-25%) in the strength of the positive potential on the molecular surface was calculated. These differences give an opportunity for fine-tuning the impact sensitivities of energetic compounds and provide new guidelines for the design of explosives with desirable characteristics.

How aromatic system size affects the sensitivities of highly energetic molecules?

Positive values of electrostatic potentials above the central regions of the molecular surface are strongly related to the high sensitivities of highly energetic molecules. The influence of aromatic system size on the positive values of electrostatic potentials and bond dissociation energies of C-NO2 bonds was studied by Density Functional Theory (DFT) calculations on a series of polycyclic nitroaromatic molecules. Calculations performed at PBE/6-311G** level showed that with the increase of the aromatic system size, values of positive electrostatic potential above the central areas of selected energetic molecules decrease from 32.78 kcal mol-1 (1,2,4,5-tetranitrobenzene) to 15.28 kcal mol-1 (2,3,9,10-tetranitropentacene) leading to the decrease in the sensitivities of these molecules towards detonation. Results of the analysis of electrostatic potential maps were in agreement with the trends in bond dissociation energies calculated for C-NO2 bonds of studied nitroaromatic molecules. Bond dissociation energies values indicate that the C-NO2 bond in the molecule of 1,2,4,5-tetranitrobenzene (56.72 kcal mol-1) is weaker compared to the nitroaromatic molecules with the additional condensed aromatic rings and with a similar arrangement of -NO2 groups (59.75 kcal mol-1 in the case of 2,3,9,10-tetranitropentacene). The influence of the mutual arrangement of -NO2 groups on the sensitivity of nitroaromatic molecules was also analyzed. Results obtained within this study could be of great importance for the development of new classes of highly energetic molecules with lower sensitivity towards detonation.

Effects of Gentiana lutea Root on Vascular Diseases.

BACKGROUND: Gentiana lutea (GL), commonly known as yellow gentian, bitter root, and bitterwort, belongs to family Gentianaceae. GL belongs to genus Gentiana, which is a rich natural source of iridoids, secoiridoids, xantones, flavonoids, triterpenoids, and carbohydrates. Medicinal plants from Gentiana species have anti-oxidant, anti-inflammatory, anti-mitogenic, anti-proliferative, and lipidlowering effects, as well as a cardioprotective, hypotensive, vasodilator and anti-platelet activities. OBJECTIVE: We reviewed the recent literature related to the effects of Gentiana species, and their active components on vascular diseases. METHODS: Data used for this review were obtained by searching the electronic database [PUBMED/ MEDLINE 1973 - February 2020]. The primary data search terms of interest were: Gentiana lutea, Gentienacea family, phytochemistry, vascular diseases, treatment of vascular diseases, antioxidant, anti-inflammatory, anti-atherogenic. CONCLUSION: Gentiana species and their constituents affect many different factors related to vascular disease development and progression. Therefore, Gentiana-based therapeutics represent potentially useful drugs for the management of vascular diseases.

Genotoxicity of fluoride subacute exposure in rats and selenium intervention.

The aims of this study were to: (i) examine the toxic effects of sodium fluoride (NaF) in blood, liver, spleen, and brain cells of Wistar rats after the subacute exposure; (ii) explore the potential protective properties of selenium (Se) against fluoride toxicity after the simultaneous administration. Twenty male Wistar rats, eight weeks old, weighing approximately 140-190 g, were divided into four experimental groups (n = 5) as follows: I control-tap water; II NaF 150 ppm; III NaF 150 ppm and Se 1.5 mg/L; IV Se 1.5 mg/L, and had available water with solutions ad libitum for 28 days. DNA damage detected by comet assay was confirmed in the liver, spleen, and brain cells, but not in blood. Selenium supplementation together with NaF decreased DNA damage in liver and spleen cells. According to the histological findings, no changes were observed in spleen and brain tissues after NaF administration. Unlike the observed Se protective effect on the DNA level, no significant reduction of liver tissue injury was observed after the NaF and Se treatment, resulting in mild inflammation. Data of this study suggest that DNA damage after NaF subacute exposure at moderately high concentration was reduced in liver and spleen cells due to Se supplementation, but a similar change was not seen in the brain.

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes.

Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.

Hyperbaric Oxygen Therapy and Vascular Complications in Diabetes Mellitus.

Vascular complications in patients with diabetes mellitus (DM) are common. Since impaired oxygen balance in plasma plays an important role in the pathogenesis of chronic DM-associated complications, the administration of hyperbaric oxygen therapy (HBOT) has been recommended to influence development of vascular complications. Hyperbaric oxygen therapy involves inhalation of 100% oxygen under elevated pressure from 1.6 to 2.8 absolute atmospheres in hyperbaric chambers. Hyperbaric oxygen therapy increases plasma oxygen solubility, contributing to better oxygen diffusion to distant tissues and preservation of the viability of tissues reversibly damaged by atherosclerosis-induced ischemia, along with microcirculation restoration. Hyperbaric oxygen therapy exerts antiatherogenic, antioxidant, and cardioprotective effects by altering the level and composition of plasma fatty acids and also by promoting signal transduction through membranes, which are impaired by hyperglycemia and hypoxia. In addition, HBOT affects molecules involved in the regulation of nitric oxide synthesis and in that way exerts anti-inflammatory and angiogenic effects in patients with DM. In this review, we explore the recent literature related to the effects of HBOT on DM-related vascular complications.