Utilizing magnetic xanthan gum nanocatalyst for the synthesis of acridindion derivatives via functionalized macrocycle Thiacalix[4]arene.

An effective method for synthesizing acridinedione derivatives using a xanthan gum (XG), Thiacalix[4]arene (TC4A), and iron oxide nanoparticles (IONP) have been employed to construct a stable composition, which is named Thiacalix[4]arene-Xanthan Gum@ Iron Oxide Nanoparticles (TC4A-XG@IONP). The process used to fabricate this nanocatalyst includes the in-situ magnetization of XG, its amine modification by APTES to get NH2-XG@IONP hydrogel, the synthesis of TC4A, its functionalization with epichlorohydrine, and eventually its covalent attachment onto the NH2-XG@IONP hydrogel. The structure of the TC4A-XG@IONP was characterized by different analytical methods including Fourier-transform infrared spectroscopy, X-Ray diffraction analysis (XRD), Energy Dispersive X-Ray, Thermal Gravimetry analysis, Brunauer-Emmett-Teller, Field Emission Scanning Electron Microscope and Vibration Sample Magnetomete. With magnetic saturation of 9.10 emu g-1 and ~ 73% char yields, the TC4As-XG@IONP catalytic system demonstrated superparamagnetic property and high thermal stability. The magnetic properties of the TC4A-XG@IONP nanocatalyst system imparted by IONP enable it to be conveniently isolated from the reaction mixture by using an external magnet. In the XRD pattern of the TC4As-XG@IONP nanocatalyst, characteristic peaks were observed. This nanocatalyst is used as an eco-friendly, heterogeneous, and green magnetic catalyst in the synthesis of acridinedione derivatives through the one-pot pseudo-four component reaction of dimedone, various aromatic aldehydes, and ammonium acetate or aniline/substituted aniline. A combination of 10 mg of catalyst (TC4A-XG@IONP), 2 mmol of dimedone, and 1 mmol of aldehyde at 80 °C in a ethanol at 25 mL round bottom flask, the greatest output of acridinedione was 92% in 20 min.This can be attributed to using TC4A-XG@IONP catalyst with several merits as follows: high porosity (pore volume 0.038 cm3 g-1 and Pore size 9.309 nm), large surface area (17.306 m2 g-1), three dimensional structures, and many catalytic sites to active the reactants. Additionally, the presented catalyst could be reused at least four times (92-71%) with little activity loss, suggesting its excellent stability in this multicomponent reaction. Nanocatalysts based on natural biopolymers in combination with magnetic nanoparticles and macrocycles may open up new horizons for researchers in the field.

Enhancement of adsorption efficiency of crystal violet and chlorpyrifos onto pectin hydrogel@Fe3O4-bentonite as a versatile nanoadsorbent.

The magnetic mesoporous hydrogel-based nanoadsornet was prepared by adding the ex situ prepared Fe3O4 magnetic nanoparticles (MNPs) and bentonite clay into the three-dimentional (3D) cross-linked pectin hydrogel substrate for the adsorption of organophosphorus chlorpyrifos (CPF) pesticide and crystal violet (CV) organic dye. Different analytical methods were utilized to confirm the structural features. Based on the obtained data, the zeta potential of the nanoadsorbent in deionized water with a pH of 7 was - 34.1 mV, and the surface area was measured to be 68.90 m2/g. The prepared hydrogel nanoadsorbent novelty owes to possessing a reactive functional group containing a heteroatom, a porous and cross-linked structure that aids convenient contaminants molecules diffusion and interactions between the nanoadsorbent and contaminants, viz., CPF and CV. The main driving forces in the adsorption by the Pectin hydrogel@Fe3O4-bentonite adsorbent are electrostatic and hydrogen-bond interactions, which resulted in a great adsorption capacity. To determine optimum adsorption conditions, effective factors on the adsorption capacity of the CV and CPF, including solution pH, adsorbent dosage, contact time, and initial concentration of pollutants, have been experimentally investigated. Thus, in optimum conditions, i.e., contact time (20 and 15 min), pH 7 and 8, adsorbent dosage (0.005 g), initial concentration (50 mg/L), T (298 K) for CPF and CV, respectively, the CPF and CV adsorption capacity were 833.333 mg/g and 909.091 mg/g. The prepared pectin hydrogel@Fe3O4-bentonite magnetic nanoadsorbent presented high porosity, enhanced surface area, and numerous reactive sites and was prepared using inexpensive and available materials. Moreover, the Freundlich isotherm has described the adsorption procedure, and the pseudo-second-order model explained the adsorption kinetics. The prepared novel nanoadsorbent was magnetically isolated and reused for three successive adsorption-desorption runs without a specific reduction in the adsorption efficiency. Therefore, the pectin hydrogel@Fe3O4-bentonite magnetic nanoadsorbent is a promising adsorption system for eliminating organophosphorus pesticides and organic dyes due to its remarkable adsorption capacity amounts.

DNA hydrogels and nanogels for diagnostics, therapeutics, and theragnostics of various cancers.

As an efficient class of hydrogel-based therapeutic drug delivery systems, deoxyribonucleic acid (DNA) hydrogels (particularly DNA nanogels) have attracted massive attention in the last five years. The main contributor to this is the programmability of these 3-dimensional (3D) scaffolds that creates fundamental effects, especially in treating cancer diseases. Like other active biological ingredients (ABIs), DNA hydrogels can be functionalized with other active agents that play a role in targeting drug delivery and modifying the half-life of the therapeutic cargoes in the body's internal environment. Considering the brilliant advantages of DNA hydrogels, in this survey, we intend to submit an informative collection of feasible methods for the design and preparation of DNA hydrogels and nanogels, and the responsivity of the immune system to these therapeutic cargoes. Moreover, the interactions of DNA hydrogels with cancer biomarkers are discussed in this account. Theragnostic DNA nanogels as an advanced species for both detection and therapeutic purposes are also briefly reviewed.

In situ preparation of MOF-199 into the carrageenan-grafted-polyacrylamide@Fe3O4 matrix for enhanced adsorption of levofloxacin and cefixime antibiotics from water.

In this research study, a novel method, an in-situ growth approach, to incorporate metal-organic framework (MOF) into carrageenan-grafted- polyacrylamide-Fe3O4 substrate was introduced. Carrageenan-grafted-polyacrylamide-Fe3O4/MOF nanocomposite (kC-g-PAAm@Fe3O4-MOF-199) was fabricated utilizing three stages. In this way, the polyacrylamide (PAAm) was grafted onto the carrageenan (kC) backbone via free radical polymerization in the presence of methylene bisacrylamide (MBA) as cross-linker and Fe3O4 magnetic nanoparticles. Next, the kC-g-PAAm@Fe3O4 was modified by MOF-199 via an in-situ solvothermal approach. Several analyses such as Fourier transform infrared spectroscopy (FT-IR), X-Ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-Dispersive X-ray Spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), Brunauer-Emmett-Teller (BET) demonstrated the successful synthesis of kC-g-PAAm@Fe3O4-MOF-199 magnetic hydrogel nanocomposite. The XRD pattern of magnetic hydrogel nanocomposite illustrated characteristic peaks of Fe3O4, neat kC, and MOF-199 with enhanced crystallinity in comparison with kC-g-PAAm@Fe3O4. TGA showed it has a char yield of 24 wt% at 800 °C. VSM confirmed its superparamagnetic behavior (with Ms of 8.04 emu g-1), and the BET surface area of kC-g-PAAm@Fe3O4-MOF-199 was measured at 64.864 m2 g-1, which was higher than that of kC-g-PAAm@Fe3O4 due to the highly porous MOF-199 incorporation with a BET surface area of 905.12 m2 g-1). The adsorption effectiveness of kC-g-PAAm@Fe3O4-MOF-199 for eliminating cephalosporin and quinolones antibiotics, i.e., Cefixime (CFX) and Levofloxacin (LEV) from the aquatic area was considered. Several experimental setups were used to evaluate the efficacy of adsorption, such as solution pH, amount of adsorbent, contact duration, and initial concentration. The maximum adsorption capacity (Qmax) of the prepared magnetic hydrogel nanocomposite was found to be 2000 and 1666.667 mg-1 for LEV and CFX using employing 0.0025 g of adsorbent. The Freundlich isotherm model well described the experimental adsorption data with R2CFX = 0.9986, and R2LEV = 0.9939. And the adsorption kinetic data were successfully represented by the pseudo-second-order model with R2LEV = 0.9949 and R2CFX = 0.9906. Hydrogen bonding, π-π interaction, diffusion, and entrapment in the hydrogel network all contributed to the successful adsorption of both antibiotics onto the kC-g-PAAm@Fe3O4-MOF-199 adsorbent. Other notable physicochemical properties include the three-dimensional structure and availability of the reactive adsorption sites. Moreover, the adsorption/desorption efficacy of magnetic hydrogel nanocomposites was not significantly diminished after four cycles of recovery.

Facile synthesis of pyrazolopyridine pharmaceuticals under mild conditions using an algin-functionalized silica-based magnetic nanocatalyst (Alg@SBA-15/Fe3O4).

Pyrazolopyridines are common scaffolds in various bioactive compounds, which have several therapeutic effects and unique pharmacological properties. In this study, we fabricated a novel environmentally friendly silica-based nanocomposite as a multifunctional catalytic system for the synthesis of pyrazolopyridine derivatives. This novel heterogeneous nanocomposite named Alg@SBA-15/Fe3O4 (Alg stands for alginic acid), was prepared in several steps. In this regard, SBA-15 was synthesized by the hydrothermal method. Next, it was magnetized by Fe3O4 nanoparticles via an in situ co-precipitation process. Then, SBA-15/Fe3O4 particles were functionalized with 3-minopropyltriethoxysilane (APTES). Afterward, Alg@SBA-15/Fe3O4 was obtained by a nucleophilic substitution reaction between SBA-15/Fe3O4-NH2 and an as-synthesized methyl-esterified alginic. Different analyses such as Fourier-transform infrared (FTIR), energy-dispersive X-ray (EDX) spectroscopy, field-emission scanning-electron microscopy (FESEM), vibrating-sample magnetometer (VSM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and BET (Brunauer-Emmett-Teller) have been used to confirm the structure of the fabricated catalyst. The magnetic properties of the Alg@SBA-15/Fe3O4 catalytic system imparted by Fe3O4 MNPs enable it to be conveniently isolated from the reaction mixture by using an external magnet. According to the obtained results, the prepared nanocatalyst has high thermal stability and it lost approximately 26% of its weight up to 800 °C. Interestingly, a small amount of prepared nanocatalyst (0.02 g) has shown excellent catalytic performance in the synthesis of pyrazolopyridine derivatives (90-97%) in a short reaction time (20-30 min) at room temperature which can be attributed to its porous structure and large surface area, and the presence of many acidic and basic functional groups. In general, it can be argued that the Alg@SBA-15/Fe3O4 nanocomposite deserves more attention due to its non-toxicity, ease of preparation, good recyclability, and its high catalytic efficiency.

A Comparative Study on the Efficacy of Coenzyme Q10 and Amitriptyline in the Prophylactic Treatment of Migraine Headaches in Children: A Randomized Controlled Trial.

Background: Migraine, one of the most common headaches in children, has a significant impact on children and their family's quality of life (QoL). There are two approaches for controlling migraine headaches preventative and controlling acute attacks. Several drugs have been used for this purpose, and tricyclic antidepressants were at the top. Amitriptyline has shown not only a desirable effect on controlling the headaches but also some adverse side effects. Recently, finding effective drugs with fewer side effects, become more critical. Among them, nutraceuticals were one of the promising ones. Materials and Methods: In this randomized clinical trial on 72 patients aged 5-15 years old with diagnosis of migraine based on the International Headache Society criteria, we compare the effectiveness of coenzyme Qten on frequency, duration, and severity of childhood migraine. For comparing the QoL, we used the International PedMIDAS questionnaire. Results: Coenzyme Qten showed good therapeutic effects in children, especially in long-term use; however, amitriptyline showed more rapid response. After 3 months of treatment, clinical outcomes in the two groups did not significantly differ from each other. Similarly, Children's QoL increased in the same way. There are more reported side effects in children using amitriptyline compared to coenzyme Qten. Conclusions: According to results, Co-enzyme Q10, with fewer side effects and comparable therapeutic effects, especially in the long term, could be a good drug for prophylactic treatment of migraine headaches.

Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.

OBJECTIVE: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683). METHODS: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterization were performed. RESULTS: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described (NM 001776.6): c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs*18), c.640del; p.(Gly216Glufs*75), c.185 T > G; p.(Leu62*), c.1531 T > C; p.(*511Glnext*100), c.967C > T; p.(Gln323*), c.414-2_414-1del, and c.146 A > G; p.(Tyr49Cys) including 4 recurrent variants c.1109 T > A; p.(Leu370*), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include childhood onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrate ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism. INTERPRETATION: The ENTPD1 locus trait consists of childhood disease onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities, with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1 (1) expands previously described features of ENTPD1-related neurological disease, (2) highlights the importance of genotype-driven deep phenotyping, (3) documents the need for global collaborative efforts to characterize rare autosomal recessive disease traits, and (4) provides insights into disease trait neurobiology. ANN NEUROL 2022;92:304-321.

The Comparison of Levetiracetam and Piracetam Effectiveness on Breath-Holding Spells in Children: A Randomized Controlled Clinical Trial.

BACKGROUND: We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood. MATERIALS AND METHODS: This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up. RESULTS: There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS. CONCLUSIONS: Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS.