Modulation of the electronic and magnetic properties of an MnCrNO2 ferromagnetic semiconductor MXene.

MXenes are members of the rapidly expanding family of two-dimensional materials known for their electronic and magnetic properties and hold significant promise for advancements in electronics and spintronics technologies. In this study, we identified a stable MnCrNO2 MXene characterized by a band gap of 2.68 eV, a magnetic moment of 6µB, and a magnetic anisotropy energy of 78.6 µeV per transition metal atom. These properties were computed using density functional theory with an on-site Coulomb potential and HSE06 hybrid functional calculations. Manipulating the band gap and magnetic properties offers considerable advantages for tailoring MXenes for specific applications. Our investigation extended to exploring the property behaviors under biaxial strain, as well as the adsorption of Group-I and Group-II ions onto the newly discovered MXene. Our findings underscore a highly linear relationship between strain and band gap, supported by an impressive R2 score of 0.997 for the best-fit straight line. Moreover, we demonstrated the linear tunability of the material's magnetic anisotropy energy under biaxial strain, achieving an R2 score of 0.982. Adsorption of 2.2% Group-I and Group-II ions onto the MnCrNO2 MXene reveals the potential for a semiconductor-to-half-metal phase transition with K, Rb, Be, Mg, and Ca ions. These results provide pathways for leveraging MXenes for the development of next-generation electronic and spintronic devices.

COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

Evaluation of possible neuroprotective effects of virgin coconut oil on aluminum-induced neurotoxicity in an in vitro Alzheimer's disease model.

Alzheimer's disease (AD) is a progressive neurological disorder that affects various cognitive functions, behavior, and personality. AD is thought to be caused by a combination of genetic and environmental factors, including exposure to aluminum (Al). Virgin coconut oil (VCO) may have potential as a natural neuroprotectant against AD. Aim of this study was to determine neuroprotective effects of VCO on Al-induced neurotoxicity in an in vitro AD model. SH-SY5Y cells were initially cultured in normal growth medium and then differentiated by reducing fetal bovine serum content and adding retinoic acid (RA). Later, brain-derived neurotrophic factor (BDNF) was added along with RA. The differentiation process was completed on the seventh day. Study groups (n = 3) were designed as control group, VCO group, Al group, Al-VCO group, Alzheimer model (AD) group, AD + Al-exposed group (AD+Al), AD + VCO applied group (AD + VCO) and AD + Al-exposed + VCO applied group (AD + Al + VCO). Specific markers of AD (hyperphosphorylated Tau protein, amyloid beta 1-40 peptide, and amyloid precursor protein) were measured in all groups. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl, and reactive oxygen species) and neurotransmitter-related parameters (dopamine, dopamine transporter acetylcholine, and synuclein alpha levels, acetylcholinesterase activity) were measured comparatively in the study groups. VCO reduced amyloid beta and hyperphosphorylated Tau protein levels in the study groups. In addition, oxidative stress levels decreased, and neurotransmitter parameters improved with VCO. Our study shows that VCO may have potential therapeutic effects in Alzheimer's disease and further experiments are needed to determine its efficacy.

Unraveling the neuroprotective mechanisms of naltrexone against aluminum-induced neurotoxicity.

Aluminum (Al) is a known neurotoxic trace element linked to Alzheimer's disease (AD). Naltrexone, an opioid antagonist, has shown promising effects in reducing neuroinflammation at lower doses than those prescribed for addiction. This study aimed to determine the neuroprotective effects of naltrexone on Al-induced neurotoxicity in an in vitro AD model. The SH-SY5Y cells were first cultivated in a standard growth medium. Subsequently, the cells were induced to differentiate by decreasing the concentration of fetal bovine serum and introducing retinoic acid (RA) into the culture media. Subsequently, the inclusion of brain-derived neurotrophic factor (BDNF) was implemented in conjunction with RA. The process of differentiation was concluded on the seventh day. Study groups (n = 3) were designed as the control group, naltrexone group, Al group, Al-Nal group, Alzheimer' model (AD) group, Alzheimer model + Al-exposed group (AD-Al), Alzheimer model + Nal applied group (AD-Nal) and Alzheimer model + Al-exposed + Nal applied group (AD-Al-Nal). Hyperphosphorylated Tau protein as the specific marker of AD was measured in all groups. Glycogen synthase kinase-3 (GSK-3)ß, Protein phosphatase 2A (PP2A), Akt and Wnt signaling pathways were analyzed comparatively. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl and reactive oxygen species) were measured comparatively in the study groups. The results showed that naltrexone reduced hyperphosphorylated tau protein levels by regulating GSK-3ß, PP2A, Akt and Wnt signaling. Also, exposure to naltrexone decreased oxidative stress parameters. Based on these results, naltrexone shows promise as a potential therapy for AD, subject to additional clinical assessments.

Evaluation of possible cytotoxic, genotoxic and epigenotoxic effects of titanium dioxide nanoparticles and possible protective effect of melatonin.

Nanoparticles (NPs) are particles of matter that are between 1 to 100 nm in diameter. They are suggested to cause toxic effects in both humans and environment thorough different mechanisms. However, their toxicity profile may be different from the parent material. Titanium dioxide (TiO2) NPs are widely used in cosmetic, pharmaceutical and food industries. As a white pigment, the use of TiO2 is used in food coloring, industrial paints, clothing and UV filters has increased tremendously in recent years. Melatonin, on the other hand, is a well-known antioxidant and may prevent oxidative stress caused by a variety of different substances, including NPs. In the current study, we aimed to comparatively investigate the effects of normal-sized TiO2 (220 nm) and nano-sized TiO2 (21 nm) on cytopathology, cytotoxicity, oxidative damage (lipid peroxidation, protein oxidation and glutathione), genotoxicity (8-hydroxydeoxyguanosine), apoptosis (caspase 3, 8 and 9) and epigenetic alterations (global DNA methylation, H3 acetylation) on 3T3 fibroblast cells. In addition, the possible protective effects of melatonin, which is known to have strong antioxidant effects, against the toxicity of TiO2 were also evaluated. Study groups were: a. the control group; b. melatonin group; c. TiO2 group; d. nano-sized TiO2 group; e. TiO2 + melatonin group and f. nano-sized TiO2 + melatonin group. We observed that both normal-sized and nano-sized TiO2 NPs showed significant toxic effects. However, TiO2 NPs caused higher DNA damage and global DNA methylation compared to normal-sized TiO2 whereas normal-sized TiO2 led to lower H3 acetylation vs. TiO2 NPs. Melatonin showed partial protective effect against the toxicity caused by TiO2 NPs.

Exploring the biointerfaces: ab initio investigation of nano-montmorillonite clay, and its interaction with unnatural amino acids.

We investigated the interaction between biomimetic Fe and Mg co-doped montmorillonite nanoclay and eleven unnatural amino acids. Employing three different functionals (PBE-GGA, PBE-GGA + U, and HSE06), we examined the clay's structural, electronic, and magnetic properties. Our results revealed the necessity of using PBE-GGA + U with U ≥ 4 eV to accurately describe key clay properties. We identified amino acids that strongly interacted with the clay surface, with steric orientation playing a crucial role in facilitating binding. Our DFT calculations highlighted significant electrostatic interactions between the amino acids and the clay slab, with the amino group's predominant role in this interaction. These findings hold promise for designing amino acids for clay-amino acid systems, leading to innovative bio-material composites for various applications. Additionally, our ab-initio molecular dynamics simulations confirmed the stability of clay-amino acid systems under ambient conditions, and the introduction of an implicit water solvent enhanced the binding energy of amino acids on the clay surface.

A snapshot of pediatric inpatients and outpatients with COVID-19: a point prevalence study from Turkey.

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027).  Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children.

Antioxidant dihydrolipolic acid protects against in vitro aluminum-induced toxicity.

Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)-induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK-3ß and the Wnt signaling pathways. The SH-SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK-3ß pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK-3ß, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/ß-catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA-treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK-3ß pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients.

Evaluation of the effects of herpes simplex glycoprotein B on complement system and cytokines in in vitro models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that causes memory loss and dementia and is characterized by a decline in cognitive functions. Brain infections, especially induced by herpes simplex virus type-1 (HSV-1), are suggested to play a key role in the pathogenesis of AD. Within the scope of this study, two different AD models (Tau model and amyloid beta [Aß]) were created in the SH-SY5Y cell line, and HSV glycoprotein B (gB) was applied to the cell line and on the generated AD models. Study groups (n = 3) were designed as (1) control, (2) HSV-gB group, (3) retinoic acid (RA) and brain derived neurotrophic factor (BDNF) induced Alzheimer's model (AD), (4) RA and BDNF induced Alzheimer's model + HSV-gB (ADH), (5) Aß 1-42 peptide-induced Alzheimer's model (Aß), and (6) Aß 1-42 peptide-induced Alzheimer's model + HSV-gB (AßH). Levels of complement proteins and cytokines were determined comparatively. In addition, specific markers of AD (hyperphosphorylated Tau proteins, Aß 1-40 peptide and amyloid precursor protein) were measured in all groups. HSV-gB administration was found to increase Aß and hyperphosphorylated Tau levels, similar to AD models. In addition, our data confirmed that the immune system and chronic inflammation might have a crucial role in AD development and that HSV-1 infection might also be an underlying factor of AD.

Estimated exposure to bisphenol A in breastfed and breastfed plus formula-fed infants in Turkey: a comparison study.

This study aimed to estimate and compare dietary exposure to bisphenol A (BPA) in exclusively breastfed (EBF) and breastfed plus formula-fed (BF + FF) infants. A total of 70 mothers and their 0-6 month-old infants (40 in the EBF group and 30 in BF + FF group) were included in the study. After the questionnaire form was applied to the mothers, maternal breast milk, infant formula, and infant urine were collected from mother-infant dyads. Total BPA levels in breast milk, infant formula, and infant urine samples were analyzed by the high-pressure liquid chromatography (HPLC). While BPA was detected in 92.5% of the breast milk samples in the EBF group (mean ± SD = 0.59 ± 0.29 ng/mL), BPA was detected in all of the breast milk samples in the BF + FF group (mean ± SD= 0.72 ± 0.37 ng/mL) (p < 0.05). Similarly, 100% of the infant formula samples in the BF + FF group had detectable levels of BPA (mean ± SD = 7.54 ± 1.77 ng/g formula). The mean urinary BPA levels in the EBF infants (4.33 ± 1.89 µg/g creatinine) were not statistically different from the BF + FF infants (5.81 ± 0.11 µg/g creatinine) (p > 0.05). The average daily BPA intake in EBF infants (0.18 ± 0.13 µg/kg body weight (bw)/day) was found to be significantly higher than in BF + FF infants (0.12 ± 0.09 µg/kg bw/day) (p < 0.05). The estimated dietary intakes of BPA for infants in both groups were below the temporary tolerable daily intake (t-TDI) (4 µg/kg bw/day). Consequently, BPA intake of EBF and BF + FF infants were within safe daily limits during the first six months of life.

Drug survival of the infliximab biosimilar (CT-P13) in paediatric patients with non-infectious uveitis.

OBJECTIVES: Paediatric non-infectious uveitis (NIU) is an important cause of significant long-term complications and blindness in children. Infliximab (IFX) is a chimeric human/murine monoclonal antibody against TNF-α that is effective in NIU resistant to conventional therapies. In this study, we aimed to determine the efficacy and safety of an IFX biosimilar (CT-P13) in paediatric patients with NIU. METHODS: This was a non-interventional and retrospective study that included paediatric patients with NIU who received IFX biosimilar CT-P13 treatment between January 2016 and January 2020. Demographic data pertaining to patients and their disease were collected. The efficacy and safety of the IFX biosimilar were evaluated. RESULTS: Twenty-six patients (44 eyes) were enrolled in this study. The median age (interquartile range) at the diagnosis of uveitis was 9.41 (5-12.3) years. The most common site of involvement was anterior uveitis, and bilateral involvement was more commonly seen in the older age group (p=0.32). The primary diagnosis of 16 patients was juvenile idiopathic arthritis, three had Behçet's disease, six had idiopathic disease and one had sarcoidosis. All patients were treated with CT-P13 (22 patients were biologic-naïve, and four switched from adalimumab). The median follow-up time on IFX was 14 months (range 4-48). Complete recovery was achieved in 95.4% of eyes with active uveitis, while inactive disease was not achieved in two of them. We observed a reduction in the number of flares in all patients during the follow-up period (4.5±2.2 vs. 0.89±1, p=0.01). Treatment-emergent adverse events occurred in 26.9% of patients. CONCLUSIONS: To our knowledge, this is the first study to assess the impact of CT-P13 treatment adherence on disease activity in children with NIU. The IFX biosimilar CT-P13 is remarkably safe and effective for the long-term treatment of paediatric NIU.

Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, albeit potentially fatal, condition in which fever, hepatosplenomegaly, and cytopenia predominate the clinical picture. Although it may be primary, it may also develop secondary to various etiologies. Herein, we aimed to report a patient who was diagnosed with pulmonary tuberculosis, developed fever and cytopenia during follow-up, and received immunomodulatory therapy together with antituberculosis therapy for the diagnosis of HLH. Sequencing of PRF1 showed heterozygous mutation. Although primary HLH has been detected in infants and children, genetic mutation of genes should be considered a differential diagnosis of HLH even in the adolescent. HOW TO CITE THIS ARTICLE: Erdogan S, Çakir D, Bozkurt T, Karakayali B, Kalin S, Koç B, et al. Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease. Indian J Crit Care Med 2020;24(1):63-65.

In pursuit of barrierless transition metal dichalcogenides lateral heterojunctions.

There is an increasing need to understand interfaces between two-dimensional materials to realize an energy efficient boundary with low contact resistance and small heat dissipation. In this respect, we investigated the impact of charge and substitutional atom doping on the electronic transport properties of the hybrid metallic-semiconducting lateral junctions, formed between metallic (1T and 1T d ) and semiconducting (1H) phases of MoS2 by means of first-principles and non-equilibrium Green function formalism based calculations. Our results clearly revealed the strong influence of the type of interface and crystallographic orientation of the metallic phase on the transport properties of these systems. The Schottky barrier height, which is the dominant mechanism for contact resistance, was found to be as large as 0.63 eV and 1.19 eV for holes and electrons, respectively. We found that armchair interfaces are more conductive as compared to zigzag termination due to the presence of the metallic Mo zigzag chains that are directed along the transport direction. In order to manipulate these barrier heights we investigated the influence of electron doping of the metallic part (i.e. 1T d -MoS2). We observed that the Fermi level of the hybrid system moves towards the conduction band of semiconducting 1H-MoS2 due to filling of 4d-orbital of metallic MoS2, and thus the Schottky barrier for electrons decreases considerably. Besides electron doping, we also investigated the effect of substitutional doping of metallic MoS2 by replacing Mo atoms with either Re or Ta. Due to its valency, Re (Ta) behaves as a donor (acceptor) and reduces the Schottky barrier for electrons (holes). Since Re and Ta based transition metal dichalcogenides crystallize in either the 1T d or 1T phase, substitutional doping with these atom favors the stabilization of the 1T d phase of MoS2. Co-doping of hybrid structure results in an electronic structure, which facilities easy dissociation of excitons created in the 1H part.

Strain enhancement of acoustic phonon limited mobility in monolayer TiS3.

Strain engineering is an effective way to tune the intrinsic properties of a material. Here, we show by using first-principles calculations that both uniaxial and biaxial tensile strain applied to monolayer TiS3 are able to significantly modify its intrinsic mobility. From the elastic modulus and the phonon dispersion relation we determine the tensile strain range where structure dynamical stability of the monolayer is guaranteed. Within this region, we find more than one order of enhancement of the acoustic phonon limited mobility at 300 K (100 K), i.e. from 1.71 × 10(4) (5.13 × 10(4)) cm(2) V(-1) s(-1) to 5.53 × 10(5) (1.66 × 10(6)) cm(2) V(-1) s(-1). The degree of anisotropy in both mobility and effective mass can be tuned by using tensile strain. Furthermore, we can either increase or decrease the band gap of TiS3 monolayer by applying strain along different crystal directions. This property allows us to use TiS3 not only in electronic but also in optical applications.

Fluorographane: a promising material for bipolar doping of MoS2.

Using first principles calculations we investigate the structural and electronic properties of interfaces between fluorographane and MoS2. Unsymmetrical functionalization of graphene with H and F results in an intrinsic dipole moment perpendicular to the plane of the buckled graphene skeleton. Depending on the orientation of this dipole moment, the electronic properties of a physically absorbed MoS2 monolayer can be switched from n- to p-type or vice versa. We show that one can realize vanishing n-type/p-type Schottky barrier heights when contacting MoS2 to fluorographane. By applying a perpendicular electric field, the size of the Schottky barrier and the degree of doping can be tuned. Our calculations indicate that a fluorographane monolayer is a promising candidate for bipolar doping of MoS2, which is vital in the design of novel technological applications based on two-dimensional materials.

Realization of a p-n junction in a single layer boron-phosphide.

Two-dimensional (2D) materials have attracted growing interest due to their potential use in the next generation of nanoelectronic and optoelectronic applications. On the basis of first-principles calculations based on density functional theory, we first investigate the electronic and mechanical properties of single layer boron phosphide (h-BP). Our calculations show that h-BP is a mechanically stable 2D material with a direct band gap of 0.9 eV at the K-point, promising for both electronic and optoelectronic applications. We next investigate the electron transport properties of a p-n junction constructed from single layer boron phosphide (h-BP) using the non-equilibrium Green's function formalism. The n- and p-type doping of BP are achieved by substitutional doping of B with C and P with Si, respectively. C(Si) substitutional doping creates donor (acceptor) states close to the conduction (valence) band edge of BP, which are essential to construct an efficient p-n junction. By modifying the structure and doping concentration, it is possible to tune the electronic and transport properties of the p-n junction which exhibits not only diode characteristics with a large current rectification but also negative differential resistance (NDR). The degree of NDR can be easily tuned via device engineering.

Doping of rhenium disulfide monolayers: a systematic first principles study.

The absence of a direct-to-indirect band gap transition in ReS2 when going from the monolayer to bulk makes it special among the other semiconducting transition metal dichalcogenides. The functionalization of this promising layered material emerges as a necessity for the next generation technological applications. Here, the structural, electronic, and magnetic properties of substitutionally doped ReS2 monolayers at either the S or Re site were systematically studied by using first principles density functional calculations. We found that substitutional doping of ReS2 depends sensitively on the growth conditions of ReS2. Among the large number of non-metallic atoms, namely H, B, C, Se, Te, F, Br, Cl, As, P, and N, we identified the most promising candidates for n-type and p-type doping of ReS2. While Cl is an ideal candidate for n-type doping, P appears to be the most promising candidate for p-type doping of the ReS2 monolayer. We also investigated the doping of ReS2 with metal atoms, namely Mo, W, Ti, V, Cr, Co, Fe, Mn, Ni, Cu, Nb, Zn, Ru, Os and Pt. Mo, Nb, Ti, and V atoms are found to be easily incorporated in a single layer of ReS2 as substitutional impurities at the Re site for all growth conditions considered in this work. Tuning chemical potentials of dopant atoms energetically makes it possible to dope ReS2 with Fe, Co, Cr, Mn, W, Ru, and Os at the Re site. We observe a robust trend for the magnetic moments when substituting a Re atom with metal atoms such that depending on the electronic configuration of dopant atoms, the net magnetic moment of the doped ReS2 becomes either 0 or 1 µB. Among the metallic dopants, Mo is the best candidate for p-type doping of ReS2 owing to its favorable energetics and promising electronic properties.

Heavy Metal and Trace Element Status and Dietary Determinants in Children with Phenylketonuria.

Background/Objectives: Heavy metals are a group of metals and metalloids that have a relatively high density. They can cause toxicity even at very low levels. Trace elements are required by all living organisms to maintain their normal growth, metabolism, and development. Oral intake is the main route of exposure to both heavy metals and trace elements. Phenylketonuria (PKU) is the most common amino acid metabolic disorder, and the best known treatment for patients requiring treatment is a phenylalanine (Phe)-restricted diet. The objective of the present study was to evaluate the plasma heavy metal levels, sources of exposure, changes in these levels according to dietary regimen, and trace element levels and their correlations with heavy metals in PKU patients. Methods: The study was conducted between July 2022 and January 2024 on 105 patients aged 2-6 years diagnosed with PKU. Results: The percentage of Pb levels in individuals in the upper quartile increased by 3.47 times (95% CI = 1.07-11.29) in those who consumed canned foods and 7.29 times (95% CI = 1.21-44.03) in those who consumed spring water. The percentage of As levels in the upper tertile increased by a factor of 7.26 (95% CI = 2.09-25.28) in individuals under four years of age and 8.17 times (95% CI = 2.13-31.27) in canned food users. The odds of having blood Cd levels in the upper tertile were 0.09 (95% CI = 0.01-0.96) for those being breastfed for 6-11 months compared to 0-5 months. Zn levels were lower (93.0 vs. 83.6 µg/dL, p = 0.008) in patients on a Phe-restricted diet. Conclusions: The present study did not find a relationship between heavy metal exposure and the dietary treatment status of patients with PKU. Our findings indicate that canned food consumption is a significant contributing factor to heavy metal exposure in PKU patients. Furthermore, our findings revealed a relationship between age, perception of economic level, breastfeeding, kitchen equipment, and water usage and the levels of certain heavy metals.

Synthesis and characterization of new hexahydroquinoline derivatives and evaluation of their cytotoxicity, intracellular ROS production, and inhibitory effects on inflammatory mediators.

Inflammation is a response to injury and infection in an organism. It can be categorized as acute or chronic. Chronic inflammation is the underlying cause of many diseases such as Alzheimer disease, diabetes, rheumatoid arthritis, atherosclerosis, and cardiovascular diseases. Recent studies have proven the antiinflammatory properties of 1,4-dihydropyridines (1,4-DHPs) and their derivatives, which have many biological activities including the blocking of calcium channels. In this study, 15 compounds that are condensed derivatives of 1,4-DHPs, with the general structure of hexahydroquinoline-3-carboxylate, were synthesized. These compounds, expected to show inhibitory activity against inflammatory mediators, were obtained by the reaction of 4-(difluoromethoxy)benzaldehyde, substituted/nonsubstituted 1,3-cyclohexanedione derivatives, and appropriate alkyl acetoacetate compounds in the presence of ammonium acetate as a nitrogen source according to the Hantzsch synthesis method. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, and HRMS methods. The cytotoxic properties of the compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in the 3T3 cell line. Among the 15 compounds, the three compounds with the lowest levels of cytotoxic effects were selected for further experiments. Inflammation was induced by lipoxygenase and the effects of the selected compounds on the levels of reactive oxygen species, cytokines, and complement C3 and C9 regulatory proteins were investigated. It was found that the three selected compounds decreased the levels of transforming growth factor-beta 1 (TGF-ß1). Among these compounds, compound 3e provided the most significant decrease in this cytokine. Moreover, 3e increased both C3 and C9 levels. Molecular modeling studies also showed that 3e had better affinity for TGF-ß1. When the binding modes of these compounds in the active site of TGF-ß1 were analyzed, it was found that compound 3e had hydrophobic interactions with amino acids Leu142, Tyr84, and Ile13; halogen bond interactions with Asp92; and hydrogen bond interactions with Ser89, Gly88, and Gly14 in the active binding site. Further in vitro and in vivo studies are needed to show the possible mechanism of action of compound 3e.

Walnut oil: a promising nutraceutical in reducing oxidative stress and improving cholinergic activity in an in vitro Alzheimer's disease model.

Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer's has become one of the priorities in the scientific world. In recent years, the beneficial effects and therapeutic properties of natural foods on neurological health have become a very remarkable issue. Walnut oil (WO) is a promising nutraceutical, with many phytochemicals and polyunsaturated fatty acids and is thought to be promising in the treatment of many neurological diseases and cognitive deficits, such as Alzheimer's disease (AD). Polyphenolic compounds found in WO enhance intraneuronal signaling and neurogenesis and improve the sequestration of insoluble toxic protein aggregates. The objective of this study was to investigate the potential protective and therapeutic effects of WO in a model of AD induced by retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). In order to achieve this, the experimental groups were formed as follows: Control group, WO group, Alzheimer's disease (AD) group, AD + WO applied group (AD + WO). WO supplementation almost significantly reduced oxidative stress in the ad model, providing 2-fold protection against protein oxidation. Additionally, WO showed a significant reduction in tau protein levels (2-fold), increased acetylcholine (ACh) levels (12%), and decreased acetylcholine esterase (AChE) activity (~50%). Since it has been known for centuries that WO does show any adverse effects on human health and has neuroprotective properties, it may be used in the treatment of AD as an additional nutraceutical to drug treatments.