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Cisplatin is an anticancer drug that can be used to treat a variety of solid tumors, where clinical use may be affected by several factors, including dose-limiting side effects and the emergence of drug resistance. Micellar-forming polymeric conjugates are a type of polymeric nanocarrier that can preferentially accumulate in tumors, thereby increasing therapeutic efficacy. In the current study, carboxylated PiPOx was synthesized first using a click reaction of 2-isopropenyl 2-oxazoline (iPOx) with thioglycolic acid (TGA) or methyl thioglycolate, followed by methyl triflate-initiated cationic ring opening polymerization (CROP). Next, different strategies were employed to prepare carboxylated PiPOx-mPEG copolymers: (a) CROP was initiated by iPOx-modified mPEG-thiol, (b) TGA-modified PiPOx were end-capped with mPEG-NH2, or (c) TGA-modified iPOx and iPOx-modified mPEG-thiol were randomly copolymerized. 1H-NMR, FT-IR, SEC, and potentiometric titration methods were used to characterize the synthesized polymers. Cisplatin-polymer conjugation was performed at three ratios of drug-to-polymer carboxyl groups (0.25, 0.5, and 1), and the conjugated cisplatin content was determined using UV–vis spectroscopy at 705 nm with O-phenylenediamine reagent. The cisplatin loading efficiencies (%) were 59.3, 26.7, and 91.0 for the respective copolymers at the chosen cisplatin/carboxyl 1:1 mol ratio. Cisplatin-conjugated PiPOx(TGA)-b-mPEG and mPEG-g-PiPOx(TGA) had mean hydrodynamic sizes of 113.3 and 178.8 nm, respectively. TEM imaging confirmed the formation of discrete and spherical particles of the cisplatin-conjugated copolymer. The MTT cytotoxicity assay demonstrated higher cytotoxicity of PiPOx(TGA)-b-mPEG compared to PiPOx(TGA)-g-mPEG polymers in both sensitive and resistant ovarian cancer cells. The IC50 values were approximately 113 µg/ml for PiPOx(TGA)-b-mPEG and 232 µg/ml for PiPOx(TGA)-g-mPEG in resistant tumor cells, confirming the potential application of cisplatin-conjugated copolymers in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease. Methods: This study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis. Results: As a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways. Conclusions: These findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals. Author summary: Leishmaniasis is a group of diseases caused by protozoan parasites belonging to the genus Leishmania. The infection involves various cells, and effective diagnosis and treatment require a clear understanding of its multiple aspects. We conducted a study using meta-analysis and feature selection algorithms combined with co-expression analysis to shed light on the key responsive genes and mechanisms involved in Leishmania infection. Our findings revealed transcriptional signatures associated with essential cellular metabolic functions and immune system response. We also confirmed the critical role of transcription factor families, including bZIP and C2H2 ZF, in response to Leishmania infection. The applied feature selection techniques identified two genes that show potential as Leishmania infection biomarkers and treatment targets. Moreover, our co-expression analysis identified seven crucial hub genes in signaling pathways. These findings provide valuable insights into the molecular mechanisms underlying the immune system cells' response to Leishmania infection and present novel potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

In this paper, we explore the noncommutative space–time to revive the idea that gamma-ray excess in the galactic center may stem from the annihilation of particle dark matter. In the noncommutative theory, the photon spectrum is produced by direct emission during this annihilation wherein a photon can be embed in the final state together with other direct products in new vertices. In the various configurations of dark matter phenomenology, we pursue the most prevalent model known as singlet scalar. Calculating the relevant aspects of the model and determining the parameters phase space, we derive the photon flux in the galactic center. This region, known for its high density and occasional existence of robust magnetic fields, serves as an ideal location for investigating theories that encompass the concept of Lorentz symmetry breaking. Upon comparing our numerical achievements with experimental data, it becomes evident that noncommutative space–time can be a reliable framework to explain the gamma-ray excess. [ABSTRACT FROM AUTHOR]

An examination was undertaken on the alkali-silica reaction (ASR) in alkali-activated slag (AAS) mixtures in comparison with ordinary portland cement (OPC) mortars and concretes. The ASR expansion in AAS mortars and concretes with different alkali contents (5%, 6%, 7%, and 8%) was examined. Changes in mechanical properties (compressive strength, tensile strength, and flexural strength) resulting from ASR expansion were evaluated. A correlation was sought between the changes in the mechanical properties of mixtures caused by ASR and ASR expansion. The test results revealed that the ASR expansion of all AAS mixtures was less than that of OPC mixtures. The expansion of AAS mixtures was below the threshold value established by the standard specifications. Additionally, it was possible to use mechanical properties to assess the occurrence of ASR due to the significant drop in these parameters caused by ASR. [ABSTRACT FROM AUTHOR]

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples. [ABSTRACT FROM AUTHOR]

Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted. [ABSTRACT FROM AUTHOR]

Objective: Intrauterine insemination (IUI) is the first-line treatment in couples suffering from various causes of subfertility and infertility. Considering the relatively low rate of pregnancy achieved with each cycle in this method, optimizing various steps in the process including the time interval from sperm collection to IUI may result in an increased rate of success. The goal of this study was to assess the impact of time intervals from the end of sperm processing to IUI (SP-IUI) on the pregnancy rate in IUI. Materials and methods: This single-center prospective cohort study evaluated couples with normal male partner sperm analysis and idiopathic female infertility undergoing IUI from 2018 to 2021. Cycles were stimulated using subcutaneous recombinant FSH and oral Letrozole. Ovulation was triggered using GnRH antagonist when the leading follicle's size reached greater than 14mm. The participants were placed in one of the three groups based on SP-IUI: group 1 (0--60 min), group II (60--90 min), and Group III: (>90 min). Results: 269 couples were included in the study. Sperm processing expectedly resulted in an increased concentration of total sperm count and sperm motility (P<0.001). The rate of chemical or clinical pregnancy, abortion, IUFD, multigestation, pregnancy, term birth, and ectopic pregnancy was not significantly different across study groups (P>0.05). Conclusion: The results of this study suggest that SP-IUI intervals evaluated in this study do not vary in terms of pregnancy rate or adverse pregnancy outcomes in IUI with normal male partner semen analysis. Hence, infertile couples can be flexible in the collection of semen specimens without time and site (at home or hospital) limitations. [ABSTRACT FROM AUTHOR]

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a–o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a–o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results. [ABSTRACT FROM AUTHOR]

Background: The magnitude of the health problems caused by leishmaniasis has been a major driving factor behind the development and implementation of leishmaniasis control programs by the national authorities in Iran, with a priority for health and environmental management. Such programs are not achievable unless all of the factors leading to the infection, including the parasite's life-cycle, vectors and reservoirs, are recognized. So far in Iran, humans and rodents have been considered the principal reservoirs of Leishmania tropica and Leishmania major, respectively, both associated with cutaneous leishmaniasis (CL), with domestic dogs considered to be the main reservoir for Leishmania infantum, associated with visceral leishmaniasis (VL). The role of other mammals in maintaining the Leishmania parasite has remained unclear. This study aimed to investigate Leishmania infection among livestock in endemic areas of VL and CL in Fars province, southern Iran, using serological and molecular methods. Methods: Blood samples from 181 clinically healthy livestock, including 49 sheep, 114 goats, 16 cattle and two donkeys, were screened to detect Leishmania DNA and anti-Leishmania antibodies using qPCR (quantitative PCR) and the direct agglutination test (DAT), respectively. Four qPCR-positive samples were amplified using the internal transcribed spacer one (ITS1) primers in conventional PCR and sent for directional sequencing. Results: Of the 181 livestock tested, 51 (28.2%) were infected with Leishmania, using serological and molecular methods. Anti-Leishmania antibodies were detected in 70 (38.7%) (95% confidence interval [CI]: 31.5–46.2) and Leishmania DNA in 93 (51.4%) (95% CI: 43.9–58.9) livestock. The identified Leishmania spp. were L. infantum and L. major. Conclusions: The findings of the present study show a relatively high prevalence of Leishmania infection among livestock in endemic areas of the disease, in Fars province, southern Iran. Given the large population of this group of animals and the fact that they live in the vicinity of the main reservoirs of the disease and vectors, it seems that sand flies regularly bite these animals. Further studies are needed to determine the role of livestock in the parasite's life-cycle and the epidemiology of Leishmania infection. [ABSTRACT FROM AUTHOR]

Background: Query ID="Q1" Text="Graphical abstract: As per journal requirements, graphical abstract is necessary. Kindly check and provide the same."The magnitude of the health problems caused by leishmaniasis has been a major driving factor behind the development and implementation of leishmaniasis control programs by the national authorities in Iran, with a priority for health and environmental management. Such programs are not achievable unless all of the factors leading to the infection, including the parasite's life-cycle, vectors and reservoirs, are recognized. So far in Iran, humans and rodents have been considered the principal reservoirs of Leishmania tropica and Leishmania major, respectively, both associated with cutaneous leishmaniasis (CL), with domestic dogs considered to be the main reservoir for Leishmania infantum, associated with visceral leishmaniasis (VL). The role of other mammals in maintaining the Leishmania parasite has remained unclear. This study aimed to investigate Leishmania infection among livestock in endemic areas of VL and CL in Fars province, southern Iran, using serological and molecular methods. Methods: Blood samples from 181 clinically healthy livestock, including 49 sheep, 114 goats, 16 cattle and two donkeys, were screened to detect Leishmania DNA and anti-Leishmania antibodies using qPCR (quantitative PCR) and the direct agglutination test (DAT), respectively. Four qPCR-positive samples were amplified using the internal transcribed spacer one (ITS1) primers in conventional PCR and sent for directional sequencing. Results: Of the 181 livestock tested, 51 (28.2%) were infected with Leishmania, using serological and molecular methods. Anti-Leishmania antibodies were detected in 70 (38.7%) (95% confidence interval [CI]: 31.5–46.2) and Leishmania DNA in 93 (51.4%) (95% CI: 43.9–58.9) livestock. The identified Leishmania spp. were L. infantum and L. major. Conclusions: The findings of the present study show a relatively high prevalence of Leishmania infection among livestock in endemic areas of the disease, in Fars province, southern Iran. Given the large population of this group of animals and the fact that they live in the vicinity of the main reservoirs of the disease and vectors, it seems that sand flies regularly bite these animals. Further studies are needed to determine the role of livestock in the parasite's life-cycle and the epidemiology of Leishmania infection. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of five alternative serodiagnostic tests, serum samples from 100 confirmed visceral leishmaniasis (VL) patients, 197 healthy endemic individuals, and 58 non-VL patients living in southern Iran were compared. The VL patients were defined as individuals with a positive result of the immunofluorescent antibody test (IFAT), having clinical signs and symptoms and appropriate response to treatment. The index tests were two direct agglutination tests, DAT-ITM (Institute of Tropical Medicine, Antwerp, Belgium) and DAT-KIT (Royal Tropical Institute, Amsterdam, The Netherlands), and three rapid diagnostic tests (RDTs), Kalazar Detect (InBios International Inc., USA), IT Leish (Bio-Rad, catalog 710124), and Leishmania test (Cypress Diagnostic Company, Belgium). Sensitivities of DAT-ITM and DAT-KIT were low, respectively, 56% and 59%, while specificities were acceptable, respectively, 98% and 93%. Observed sensitivities and specificities of RDTs were higher (71%, 81%, 70% and 99%, 99%, 98% for Kalazar Detect, IT Leish, and Leishmania test, respectively). Even with a maximum sensitivity of 81%, RDTs missed almost one-fifth of VL patients that were positive in IFAT. We conclude that RDTs in VL patients do not possess adequate performance in southern Iran and require some improvement, but they can still be helpful in the diagnosis and screening of the disease in this region due to their high specificity and speed. [ABSTRACT FROM AUTHOR]

UMP2 calculations with aug-cc-pVTZ basis set used to analyse intermolecular interactions in X3C···PH2Y···ClY (X = H, CH3; Y = CN, NC) complexes constructed via halogen bond and single-electron pnicogen bond in two discovered minima in the potential energy surface. The first minima presents short P−C distances and, in all cases, high interaction energies compared to the second one that shows long P−C distances with a typical weak pnicogen bond interaction. The impacts of the halogen bonds on the single-electron pnicogen interaction in each complex are systematically investigated by the means of cooperative effects. In all cases studied, a favorable cooperativity is observed but these values are much higher for first minima, which ranges from −19.73 to −36.82 kJ mol−1, than second minima with cooperative energy values between −0.75 and −4.69 kJ mol1. In order to unveil the mechanism of the cooperativity, these effects are analysed in terms of geometric, energetic, electrostatic potential analysis, electron charge density analysis performed using (QTAIM), many-body interaction analysis and electron density analysis. [ABSTRACT FROM AUTHOR]

Background and aims: COVID-19 is a pandemic and infectious disease with high morbidity and mortality rates as well as a global spread. This study aimed to investigate the clinical outcomes for patients afflicted with COVID-19 and treated with remdesivir. Methods: In this clinical trial study, patients with severe COVID-19 confirmed by molecular testing and hospitalized at Hajar Hospital of Shahrekord in Iran were divided into standard care group (including 52 patients) and standard + remdesivir group (including 51 patients). The patients were examined for clinical symptoms, laboratory data, as well as mortality and recovery rates during the treatment period. Then the data were analyzed by SPSS version 23 using chi-square, independent t-test and repeated-measures ANOVA. Result: Clinical and laboratory monitoring on days 5, 10, and 14 showed that there was no significant difference between two groups (P>0.05). In addition, there was no significant difference between the two groups in terms of hospitalization duration and ICU rate (58.8% versus 51.9%, P=0.48). The trend of Lymph count and platelet decreased significantly in the standard group (P=0.003, P=0.04, and P=0.03, respectively). Conclusion: Patients with severe COVID-19 were investigated and it was concluded that remdesivir produced no improvement in the remdesivir group compared to the standard group. [ABSTRACT FROM AUTHOR]

[Display omitted] • The VHH displaying phage fabricated for VEGF detection. • The preparation and operation simplified by labeling steps elimination. • The results revealed excellent specificity and reliability of proposed immunosensor. • Analysis of results showed valuable LOD, LOQ and wide linear range. Herein the pioneering label-free electrochemistry-based immunosensor with exceptional sensitivity for the rapid and efficient detection of vascular endothelial growth factor (VEGF) was precisely designed based on the phage display technique. The specific variable domain of a heavy-chain antibody (VHH)-displaying phage against VEGF 8–109 was successfully immobilized on Au nanoparticles deposited gold electrode modified by 3-mercapto propionic acid and 11-mercaptoundecanoic acid and then, carbodiimide coupling reaction using N-hydroxysuccinimide and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. Electrochemical characterizations of the proposed immunosensor were performed by PM-FT-IRRAS, scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy techniques. Electrochemical measurements were performed using differential pulse voltammetry in phosphate buffer containing [Fe(CN) 6 ]3–/4– ions as a probe, where the decline in the peak current value was related to a concentration of the antigen cast on the surface of the immunosensor. Under the optimum conditions (pH 7.4, interval time 20 s, and step potential 0.1 V), a linear range of response for the detection of VEGF 8–109 by immunosensor was 0.03–10,000 pg/mL (in log concentration), with a limit of detection of 11 fg/mL. The specificity of the immunosensor was also investigated against some typical blood growth factors. The novel immunosensor was applied to evaluate VEGF levels in human serum specimens clinically. The recommended immunosensor was uncomplicated, reasonably priced, and showed adequate accuracy and specificity, which could be applied in the early diagnosis of tumors. [ABSTRACT FROM AUTHOR]

Background: Blastocystis sp., located in the large intestine, is one of the most common zoonotic parasites. Risk factors affect its prevalence and pathogenicity, and it causes gastrointestinal disorders. Thus, this study aimed to investigate the Blastocystis sp. prevalence and its relationship with gastrointestinal disorders, in patients referred to laboratories, and provide some prevention strategies. Methods: In this descriptive-analytical study, 1,000 stool specimens were collected from patients referred to Ilam, Iran laboratories from 2018-2019. Wet mount method was conducted on samples, and suspected specimens were confirmed using trichrome staining. The demographic and clinical information was recorded in a questionnaire. Finally, the results were analyzed using the SPSS. Results: Blastocystis infection was detected in 81 out of 1,000 patients (8.1%) including 61 (75.3%) males and 20 (24.7%) females. and illiterate people were more at risk. The prevalence in rural was more than urban areas, and it was more in the age group of 31-50 year. Conclusion: There was a significant relationship between Blastocystis sp. and risk factors (age, sex, level of education, and residence) and clinical symptoms (stomach ache and nausea) (P<0.05), but interestingly there was no significant relationship between bloating and diarrhea. [ABSTRACT FROM AUTHOR]

Synthesis of a new class of 2-[1-({[2,2,2-trifluoro-1-(arylamino)ethylidene]amino}methyl)cyclohexyl]acetic acids and 2,2,2-trifluoro-N-({1-[2-oxo-2-(arylamino)ethyl]cyclohexyl}methyl)acetamides are described by one-pot reaction of gabapentin and trifluoroacetimidoyl chlorides in the presence and absence of titanium dioxide nanoparticles (TiO2-NPs) as a catalyst and sodium hydride as a base under an N2 atmosphere. Subsequently, a series of potentially biologically active of 2-[1({[(dialkoxyphosphoryl)(phenyl)methyl]amino}methyl)cyclohexyl] acetic acid derivatives were synthesized via reaction of gabapentin, benzaldehyde imino derivatives and trialkyl phosphites in the presence of I2/CH3COOH as catalyst. The structures of products are supported by FT-IR, ¹HNMR, 13C-NMR, 19F-NMR spectral and X-Ray crystallography data. [ABSTRACT FROM AUTHOR]

Background. Toxoplasma gondii is an intracellular protozoan parasite responsible for systemic disease in a wide range of warm-blooded animals. The current study is aimed at evaluating the prevalence of Toxoplasma infection in dogs, using serological and molecular methods in rural areas in Kazeroun Township, Fars province, southern Iran. Methods. Blood samples were obtained from 60 clinically healthy dogs with an age range of 1 to 7 years in three rural areas of Fars province, southern Iran. Sera and buffy coats were used to assess the T. gondii infection using both modified agglutination test (MAT) and real-time PCR. Results. Antibodies against T. gondii were detected in 5 out of 60 (8.3%) dogs by the MAT method, and T. gondii DNA was detected in 17 out of 60 (28.3%) studied animals. There was no significant association between sex and seropositivity to Toxoplasma (p > 0.05). Fair agreement (kappa = 0.27) was seen between molecular and serological findings where three dogs with positive serological results had a positive molecular test. Conclusion. Findings of the present study show a relatively high prevalence of T. gondii infection in dogs in rural areas in Fars province, southern Iran. Finding the parasite genotype in dogs deserves further study. [ABSTRACT FROM AUTHOR]

Deficiency of the proteins involved in oxidative phosphorylation (OXPHOS) can lead to mitochondrial dysfunction. Polyribonucleotide nucleotidyltransferase 1 (PNPT1) is one of the genes involved in the OXPHOS and encodes the mitochondrial polynucleotide phosphorylase (PNPase) which is implicated in RNA-processing exoribonuclease activity. Herein, we report a 34-month-old boy who presented with global developmental delay, muscular hypotonia, hearing impairment, and movement disorders including chorea and dystonia. Mitochondrial genome sequencing and whole-exome sequencing (WES) were performed and a variant in PNPT1:c.1453A>G; p. (Met485Val) was identified. A number of patient's neurologic problems had been already reported in previous studies, however, lower limbs spasticity and bulbar dysfunction were novel phenotypic findings. In addition, delayed myelination during infancy, progressive basal ganglia atrophy, and brain stem abnormal signals including transverse pontine fibers and superior colliculus involvement were also novel neuroimaging findings in this case. Different crystallographic modeling and stereochemical analysis of the c.1453A>G; p. (Met485Val) variant showed this variant affects the active site of the protein and disrupts the normal protein function. [ABSTRACT FROM AUTHOR]

Introduction: Successful frozen-thawed embryo transfer (FTET) depends on multiple factors among which the woman's vaginal microbiota has recently been considered important. Using probiotic products, such as Lactovag in infertile women, the vaginal microbiome can become close to the healthy status. Objectives: The aim of this study was to evaluate the effect of Lactovag on normalizing vaginal microbiome, as well as its role in improving pregnancy outcomes in FTET cycles. Patients and methods: This randomized blinded clinical trial was conducted on 103 patients undergoing Assisted Reproductive Technology (ART) treatment at a tertiary university-based hospital between January and August of 2019. In the experiment group, the vaginal suppository Lactavag was prescribed, whereas in the control group, patients did not receive any microbiome supplements. Then, the pregnancy rate was compared in the two groups. Results: There were no significant differences in baseline characteristics between the two study groups (p > 0.05). Positive B hCG was present in 28% (n = 26) of women, clinical pregnancy was achieved in 23.4% (n = 22) of them and fetal heart rate was detected in 21.3% (n = 20). These proportions were higher in the Lactovag group, although these differences were not significant (p > 0.05). Results showed that although transferring fetuses with grade A increased the odds of pregnancy with 1.53 (p = 0.001) folds, this ratio would be improved using Lactovag;1.68 (P value = 0.008). Conclusions: It seems that the vaginal microbiota critically interplays with women's health and reproduction. A probiotic agent such as Lactovag can be useful in normalizing this environment and improving pregnancy outcomes in infertile women. [ABSTRACT FROM AUTHOR]

Heart disease is the leading cause of death worldwide and imposes a significant burden on healthcare systems globally. A major hurdle to the development of more effective therapeutics is the reliance on animal models that fail to faithfully recapitulate human pathophysiology. The predictivity of in vitro models that lack the complexity of in vivo tissue remain poor as well. To combat these issues, researchers are developing organ-on-a-chip models of the heart that leverage the use of human induced pluripotent stem cell-derived cardiomyocytes in combination with novel platforms engineered to better recapitulate tissue- and organ-level physiology. The integration of novel biosensors into these platforms is also a critical step in the development of these models, as they allow for increased throughput, real-time and longitudinal phenotypic assessment, and improved efficiency during preclinical disease modeling and drug screening studies. These platforms hold great promise for both improving our understanding of heart disease as well as for screening potential therapeutics based on clinically relevant endpoints with better predictivity of clinical outcomes. In this review, we describe state-of-the-art heart-on-a-chip platforms, the integration of novel biosensors into these models for real-time and continual monitoring of tissue-level physiology, as well as their use for modeling heart disease and drug screening applications. We also discuss future perspectives and further advances required to enable clinical trials-on-a-chip and next-generation precision medicine platforms. • Review of recent advances in the design of heart-on-a-chip platforms. • Review of novel biosensors integrated into heart-on-a-chip devices. • Review of disease modeling and phenotypic drug screening in heart-on-a-chip platforms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Low-intensity BLA electrical stimulation by itself induces reward responses. • High-intensity BLA electrical stimulation suppresses morphine-induced CPP. • BLA blockade with lidocaine suppresses morphine-induced CPP. In the present study, to evaluate the role of the basolateral amygdala (BLA) in morphine addiction, the BLA was stimulated electrically, or inactivated temporarily using lidocaine. The electrical stimulation (ES) was delivered to BLA with low or high intensities (LI or HI: 25 or 150 µA, respectively), and five minutes before morphine administration with effective or ineffective doses, lidocaine was microinjected into the BLA. Using a 5-day conditioned place preference (CPP) paradigm, the dependence on morphine was evaluated. The results showed that LI-ES of BLA induced CPP in both the acquisition and expression phases, in the control and the ineffective dose of morphine groups. HI-ES had no effect on CPP acquisition but induced aversion in the expression, with both effective and ineffective doses of morphine. Inactivation of BLA using lidocaine, inhibited morphine-induced CPP in both acquisition and expression phases. The results of the present study indicate the prominent role of BLA in morphine addiction and dependence. Considering the contradictory results of different intensities of ES, it can be inferred that there are different neural circuits in this area of the brain, in relation to the reward responses. [ABSTRACT FROM AUTHOR]

• The scope of this research limited to papers between 2016 and 2020 years. • Breast imaging, segmentation, feature extraction, and tumor classification are investigated. • A summary of each category is presented at the end of each subsection. • The main issues and gaps in the existing approaches are discussed. • Available software and datasets are introduced. The breast cancer as the most life-threatening disease among the woman has emerged in the worldwide. It is supposed that the early testing and treatment for breast cancer detection would be avoided the surgeries and increase the survival rate. A variety of research studies have motivated to improve the diagnostic methods for early diagnosis of breast cancer. This study investigates the automatic and semi-automatic image-based approaches for breast cancer diagnosis. The scope of this research has limited to the images based diagnosis application journal that are published between 2016 and 2020 years. The principles and associated risk factors for diagnosis the breast cancer and existing imaging techniques are presented. The steps of diagnosis including preprocessing, segmentation, extracting tumor features, and tumor classification are investigated. The publicly available datasets for breast imaging are briefly introduced as well. The application issues, challenges of breast imaging technologies and future directions are discussed. Based on the detailed study, most proposed methods use one type of imaging modalities, however, the doctor need to investigate the multiple imaging techniques to accurate diagnosis and effective treatment. Moreover, handling the multiple imaging require the processing of big data using a cluster computing framework. [ABSTRACT FROM AUTHOR]

Study of the mechanism of heavy quarkonia production is a powerful tool for a better understanding of the dynamics of strong interactions and probably to search for new physics. It is well-known that the fragmentation mechanism is dominant for heavy quarkonia production and forms the nonperturbative aspect of hadron production. Since the main contribution of J ∕ ψ production in high energy processes results from the gluon fragmentation, through this work, we study the fragmentation mechanism of gluon into S-wave vector heavy charmonium J ∕ ψ at lowest order perturbative QCD and extend our work to the noncommutative standard model. To investigate the effects of space–time noncommutativity, we employ the Seiberg–Witten maps. Our results show that the noncommutative effects are considerable, specifically when the gluon transverse momentum is small; p T < 3 0 GeV. [ABSTRACT FROM AUTHOR]

Background: Infertility is a relatively common problem that ovarian and tubular causes are the most important factors involved that can also be treated. One of its diagnostic methods is hysterosalpingography, which is a cheap and non-invasive method. The aim of this study was to compare the prophylactic effectiveness and side effects of azithromycin and doxycycline in the prevention of PID after hysterosalpingography in infertile women. Materials and Methods: This randomized, double-blind clinical trial was performed on women who underwent hysterosalpingography for the cause of infertility. Patients were randomly divided into two groups of 90. The control group received standard prophylaxis with two doses of doxycycline (100 mg) 24 hours before the procedure. The second group received prophylactic treatment with 500 mg azithromycin (single dose). Follow-up of all patients was performed 14 days after hysterosalangography for signs of pelvic inflammatory disease and possible side effects of drugs. After data collection, data analysis was performed using SPSS statistical software version 25. Results: The incidence of PID after hysterosalpingography procedure in patients receiving doxycycline and azithromycin was 6.7% and 13.3%, respectively. No significant difference was found between the incidence of PID using the prophylactic antibiotics in the two groups (P = 0.13). Complications of prophylactic antibiotics were reported only in patients receiving doxycycline, including nausea (10%), vomiting (3.3%), and abdominal pain (3.3%). In the azithromycin group, 1.1% had nausea and 2.2% had diarrhea, which showed a significant difference between the side effects of the prophylactic antibiotics in the two groups (P = 0.004). There was a significant difference between patients' satisfaction with the use of prophylactic antibiotics in the two groups (P = 0.002). Also, the low level of satisfaction in the doxycycline group compared to the azithromycin group was due to gastrointestinal side effects in the first group. Conclusion: Administration of doxycycline prophylactic antibiotic in the prevention of PID infection was not significantly different compared with azithromycin. The incidence of PID was slightly higher in patients receiving azithromycin than in doxycycline. Patients' satisfaction with doxycycline was lower due to gastrointestinal side effects when compared with patients receiving azithromycin who had no gastrointestinal side effects. [ABSTRACT FROM AUTHOR]

Today, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient compounds with higher resistance are needed. In this study, a series of a fluconazole analogues were subjected to quantitative structure-activity relationship analysis to find the structure requirements for modeling adequate candidate. The best multiple linear regression equation was achieved from GA-PLS and MLR modeling. Subsequently, in silico screening study was applied to found new potent lead compounds based on the resulted model. The ability of the best designed compounds for antifungal activity was investigated by using molecular dynamic (MD) and molecular docking simulation. The results showed that compound F13 can efficiently bind to lanestrol 14-α demethylase target similar to other antifungal azoles. The molecular docking studies revealed an interesting binding profile with very high receptor affinity to the CYP51 active site. The triazole moiety of ligand F13 pointed to HEM group in lanestrol 14-α demethylase site and coordinated to Fe of HEM through its N4 atom. Also, there was a convenient relevance between QSAR and docking results. With the compound F13 which demonstrated the most promising minimum inhibitory concentration (MIC) values, it can be concluded that F13 is appropriate candidate for the development as antifungal agent. [ABSTRACT FROM AUTHOR]

Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. This study summarizes the clinical, imaging, and molecular data of these patients for five years. The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1 , and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042). [ABSTRACT FROM AUTHOR]

Canine visceral leishmaniasis (CVL) is endemic in the southern parts of Iran. The current study aimed at molecular and serological evaluation of zoonotic visceral leishmaniasis in dogs in Fars province, southern Iran. Blood samples were collected from 60 dogs in the three villages in Fars Province. Serum samples were tested for antibodies against L. infantum by direct agglutination test (DAT). DNA was extracted from each dog's buffy coat and tested by PCR, targeting the Leishmania ITS‐2 region. From a total of 60 studied dogs, 25 (41.7%) were female, and 35 (58.3%) were male. Dogs' age ranged from 1 to 7 years, with a mean age of 2.97 (±1.4) years. Anti‐Leishmania antibodies were detected in sera samples of 28 (46.7%) dogs, (titre ≥ 1:320). Out of 28 seropositive cases, 13 (46.4%) were female, and 15 (53.6%) were male. Association between seropositivity and dogs' clinical signs was statistically significant (p <.05). Leishmania DNA was detected in the buffy coat of 3 of 60 studied dogs which were all seropositive by DAT. The PCR products were sequenced and molecular analysis showed that two of the isolates were Leishmania infantum, and one was L. tropica. The high proportion of seropositive dogs indicates the important role of these animals in the epidemiology of the disease in the region. Infected dogs with or without signs, especially those that are molecularly positive, can act as an active reservoir of the disease in the area. [ABSTRACT FROM AUTHOR]

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil–azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure–activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil–azole hybrids can be considered as potential cytotoxic agents. [ABSTRACT FROM AUTHOR]

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, educational programs have increasingly relied on virtual methods. Objectives: In this study, we compared the effects of in-person and virtual electroencephalography (EEG) training on the knowledge of pediatric and adult neurology residents. Methods: The study participants consisted of 30 pediatric and adult neurology residents who were recruited nationwide via a virtual network. They were randomly divided into two groups for in-person and virtual education, respectively. Prior to the first workshop session, participants completed a pre-test comprising 19 knowledge-related questions. Two interactive training sessions focusing on benign variants in EEG were conducted, including two in-person workshops for eight residents and two online workshops for 22 residents. Each session lasted one hour, with one held every two weeks. After the second session, participants were asked to complete a post-test consisting of 24 questions (identical to the pre-test) and five workshop satisfaction-related questions. Results: Overall, the mean exam score after both the in-person and virtual workshops was significantly higher than the pretest score across all educational levels. The mean score differences in knowledge between the in-person and virtual groups after the workshop were similar, with no statistically significant difference. Approximately 90% of the participants believed that the workshop would be beneficial for their daily practice. Conclusions: Given the absence of a significant difference between in-person and virtual training methods in improving participants' knowledge and satisfaction with both approaches, we recommend integrating virtual EEG training into the educational protocol for pediatric and adult neurology residents. Nonetheless, larger sample size studies are required to further validate these findings. [ABSTRACT FROM AUTHOR]

In this study, two series of novel 1,4-benzothiazine-3-one derivatives with alkyl substitution (series 1: 4a-4f) and aryl substitution (series 2: 4g-4l) were designed and synthesized based on the chemical scaffolds of perampanel, hydantoins, progabide and etifoxine as anti-convulsant agents. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1H NMR and 13C NMR spectroscopy. Anti-convulsant effect of the compounds was examined through intraperitoneal pentylenetetrazol (i.p. PTZ) induced epilepsy mouse models. Compound 4h (4-(4-bromo-benzyl)− 4 H-benzo[ b ] [1,4] thiazin-3(4 H)-one) demonstrated a promising activity toward chemically-induced seizure experiment. Molecular dynamics simulation on GABA-Aergic receptors as a plausible mechanism were also done to achieve the binding and orientation of compounds in the active site of the target to evaluate the results of docking and experimental studies. The computational results were confirmed the biological activity. DFT study of 4c and 4h was performed on B3LYP/6–311 G** level of theory. Reactivity descriptors such as HOMO, LUMO, electron affinity, ionization potential, chemical potential, hardness and softness were studied in detail and show that 4h has higher activity than 4c. Also, the frequency calculations were performed on the same level of theory and the results are in line with experimental data. Moreover, in silico ADMET properties were done to establish a relationship between the physiochemical data of the designed compounds and their in-vivo activity. Appropriate plasma protein binding and high blood-brain barrier penetration are the main features of desired in -vivo performance. [Display omitted] • 1,4 benzothiazine 3-one derivatives were synthesized as anticonvulsant agents. • The benzothiazine containing 4-bromo-benzyl substitution, increased the latency of convulsions. • The computational studies and biology assay indicated that compound 4h might had a good inhibitory effect on GABA-A receptor. • The results of the computational study and experimental methods about compound 4h were agreement together. [ABSTRACT FROM AUTHOR]

Background: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. Methods: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. Results: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% − 1.10, and upper 95% − 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype–phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. Conclusion: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype. [ABSTRACT FROM AUTHOR]

Background: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease‐causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families. Methods: Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole‐exome sequencing (WES) was undertaken in order to detect disease‐causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013–2020. Results: Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7‐year‐old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN‐1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory‐motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features. Conclusions: One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis. [ABSTRACT FROM AUTHOR]

• The use of alkali-activated slag can be an efficient way to reduce ASR expansion in concrete. • The ASR expansion and electrical resistivity of concrete were correlated. Electrical resistivity reduced as expansion caused by ASR increased. • The occurrence of ASR can affect the mechanical properties of concrete. Utilizing alkali-activated slag (AAS) as a cement replacement material has significantly reduced the cement industry's overall carbon footprint while enhancing the potential for the improved technical performance of concrete. However, using activators with high alkalinity has the potential to result in Alkali-Silica Reaction (ASR) in concrete containing reactive aggregates, which restricts its application in commercial settings. The occurrence of ASR can cause changes to the mechanical properties of concrete due to the development of delayed cracks. Therefore, designing a concrete structure necessitates determining the extent to which concrete is susceptible to ASR. In this paper, mechanical strength tests were conducted to assess the effect of ASR on the properties of concrete. In addition, electrical resistivity measurement was utilized to investigate the occurrence of ASR in concrete mixtures containing AAS and reactive aggregates. The correlation between ASR expansion and electrical resistivity was examined. Reference mixture and AAS concrete mixtures with varying alkali/slag (Al/slag) ratios were prepared for this purpose. The results showed a good correlation between the electrical resistivity data and the expansion caused by ASR. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) is one of the most successful parasites in the world, because about a third of the world's population is seropositive for toxoplasmosis. Treatment regimens for toxoplasmosis have remained unchanged for the past 20 years, and no new drugs have been introduced to the market recently. This study, performed molecular docking to identify interactions of FDA-approved drugs with essential residues in the active site of proteins of T. gondii Dihydrofolate Reductase (TgDHFR), Prolyl-tRNA Synthetase (TgPRS), and Calcium-Dependent Protein Kinase 1 (TgCDPK1). Each protein was docked with 2100 FDA-approved drugs using AutoDock Vina. Also, the Pharmit software was used to generate pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS in complex with halofuginone, and TgCDPK1 in complex with a bumped kinase inhibitor, RM-1–132. Molecular dynamics (MD) simulation was also performed for 100 ns to verify the stability of interaction in drug–protein complexes. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis evaluated the binding energy of selected complexes. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and Lactulose drugs against the TgPRS protein, and Pentaprazole, Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed the best results. These drugs had the lowest energy-based docking scores and also stable interactions based on MD analyses with TgDHFR, TgPRS, and TgCDPK1 drug targets that can be introduced as possible drugs for laboratory investigations to treat T. gondii parasite infection. [ABSTRACT FROM AUTHOR]

Resistance of Candida species is a major problem in the management of Candida infection. This study investigated in vivo antifungal activities of several new imidazole and triazole derivatives in a C. albicans systemic infection. The efficacy of derivatives was determined against systemic infection by C. albicans in mice with cyclophosphamide-induced immunosuppression, and the antifungal activities of the synthesized compounds were evaluated in comparison with fluconazole. Compounds 3 and 8 had the highest efficacy with minimum inhibitory concentration (MIC) values of 0.5–1 μM against the C. albicans pathogen. In vivo activities in immunosuppressed mice were also greater than fluconazole. Furthermore, docking analysis was carried out to know the binding mode of imidazole and triazole derivatives to the CYP51 active site of C. albicans and dihydrofolate reductase as a valid antifungal target. The docking study found that the antifungal results are well correlated with docking results. ADMET and in silico physicochemical parameters were also performed. This study demonstrates that compounds 3 and 8 are potential antifungal candidates against the C. albicans pathogen. [ABSTRACT FROM AUTHOR]

Background: Mental disorders can significantly impact maternal health and neonatal health and development. This study investigated maternal anxiety, depression, and stress during pregnancy concerning their children's development. Methods: In this follow-up study, all pregnant women with gestational age > 12 weeks referring to an obstetrics and gynecology clinic affiliated with Shahid Sadoughi University of Medical Sciences over six months were included. Data on mothers were collected using a personal information questionnaire and the Depression Anxiety Stress Scale (DASS)-42 standard questionnaire. Finally, based on the inclusion and exclusion criteria, the children of 73 mothers were included in the study. Infant development was assessed based on the Persian version of the Ages and Stages Questionnaire (ASQ) at six months postpartum. Data analysis was conducted using the Pearson correlation test and multiple regression analysis. Statistical analyzes were carried out using SPSS 21. A P-value <0.05 was considered statistically significant. Results: In this study, 39.7%, 63%, and 56.2% of women suffered from depression, anxiety, and stress, respectively. In this study, a significant relationship was found between antenatal maternal depression and gross motor (P: 0.022), fine motor (P: 0.003), personal-social (P: 0.009), and communication skills (P: 0.0180). Moreover, there was a significant relationship between maternal anxiety and personal-social (P: 0.012) and gross motor domains (P: 0.008). Also, a significant association was observed between personal-social skills and maternal stress (P: 0.030). Conclusion: As shown by the results, antenatal maternal mental illness can interfere with the development of children. Therefore, paying attention to the mental health of pregnant women is necessary. [ABSTRACT FROM AUTHOR]

We reported an association between SARS‐CoV‐2 infection and Guillain–Barre syndrome (GBS). From 37 patients with GBS, previous SARS‐CoV‐2 clinical clues, including fever, cough, and diarrhea, were recorded in 18 patients. Among them, SARS‐CoV‐2 IgG was detected in seven patients, considered confirmed as cases. SARS‐CoV‐2 PCR was positive in just one patient. Although we found no increase in patient recruitment during the pandemic compared to previous years, our study indicated that SARS‐CoV‐2 is associated with poorer outcomes regarding GBS disability scale and hospital stay. Although the rate of Guillain–Barre syndrome in children associated with SARS‐CoV‐2 was the same as previous years, it would be related to more hospital stay and serious complications that is necessary for pediatric neurologists to mention. [ABSTRACT FROM AUTHOR]

Herein, we reported the synthesis of nineteen novel 1,2,4-triazole derivatives including 1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl) propan-1-ones (7a-e), 1-(1,3-diphenylpropan-2-yl)-1H-1,2,4-triazole (8a-c) and 1,4-diphenyl-2-(1H-1,2,4-triazol-1-yl) butane-1,4-diones (10a-k). The structures of these derivatives were confirmed by spectroscopic techniques like IR, 1H-NMR, Mass spectroscopy and Elemental analysis. The cytotoxic activities of the synthesized compounds were evaluated against three human cancer cell lines including MCF-7, Hela and A549 using MTT assay. Compounds 7d, 7e, 10a and 10d showed a promising cytotoxic activity lower than 12 μM against Hela cell line. The safety of these compounds was also, evaluated on MRC-5 as a normal cell line and relieved that most of the synthesized compounds have proper selectivity against normal and cytotoxic cancerous cell lines. Finally, molecular docking studies were also, done to understand the mechanism and binding modes of these derivatives in the binding pocket of aromatase enzyme as a possible target. [ABSTRACT FROM AUTHOR]

In this study, the role of hydro-alcoholic extract of BS on obesity and its related hormones neuropeptide-Y (NPY), agouti protein, leptin, insulin, ghrelin, cholecystokinin, amylin, orexin, obestatin, adiponectin, chemerin, omentin-1, epinephrine, resistin, kidney and liver function markers and antioxidants were investigated. Thirty-six male Wistar rats were divided into six groups: Control, Sham, and hydroalcoholic BS extract groups (four doses): 200, 400, 800, and 1600 mg/kg. The extract was fed by gavage, and after 29 days, blood samples and tissues were taken. Rats ELISA kits were used to measure adiponectin, obestatin, resistin, orexin A, insulin, epinephrine, AgRP, omentin, chemerin, amylin, agitation, NPY, and ghrelin. In addition, we measured leptin, cholecystokinin, lipid profile factors, kidney and liver function markers and antioxidants. Evaluating weight changes demonstrated that using BS help animals to lose weight significantly in groups received 800 and 1600 mg/kg BS. Leptin, adiponectin, AgRP, obestatin, CCK, chemerin, adiponectin, and total antioxidants showed a significant increase compared to the control group, while ghrelin, lipid profile, resistin, orexin A, omentin, amylin, epinephrine, MDA, and NPY were reduced at treatment groups. Using BS affected patients’ kidney and liver function. Higher doses of BS was more effective than lower. The blood creatinine was not affected by BS. These findings suggest that BS reduces NPY and orexin, thereby prevent appetite. BS also reduces ghrelin and increases obestatin, and cholecystokinin; BS has the potency to alter adipose tissue secretory factors to help with weight loss and reduce the lipid profile, which affects patients’ health. [ABSTRACT FROM AUTHOR]

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S1–S11) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe3O4–Ti(IV)) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S10 and S11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ‐aminobutyric acid A (GABA‐A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S10) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S11 can be to become a potential drug candidate as an anticonvulsant agent. [ABSTRACT FROM AUTHOR]

In recent years, resistance to conventional antimicrobial drugs has become a serious concern in the clinic. Hence, the discovery of novel and effective antimicrobial agents with improved properties is of great value. In this study, the antibacterial and anticandidal activities of some imidazole, benzimidazole and benztriazole derivatives (C1-C8) against several species of Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Salmonella typhi as well as one species of fungi including Candida albicans, were evaluated using Clinical & Laboratory Standards Institute (CLSI) method. Antimicrobial evaluation revealed that among the tested compounds, imidazole derivative (C5) indicated the highest activity against bacterial strains and Candida albicans. It was found that compound C5 is more potent than ampicillin against S. aureus strain (MIC =2-16 µg/mL) and possessed excellent anticandidal activity (MIC =1 µg/mL) which was comparable to Amphotericin B as the positive control. In addition, cytotoxic activity of the tested compounds was investigated using MTT assay. The results of MTT assay demonstrated that the toxicity of the tested compounds was less than 35%. [ABSTRACT FROM AUTHOR]

Our attention was then turned to the possibility of recycling the catalyst from the reaction media since the recovery and reuse of the catalyst are preferable for a green context. At the completion of the reaction, the reaction mixture was poured into chloroform and stirred for 5 min. The desired products were formed in negligible yields, suggesting that BaSO SB 4 sb is not a suitable catalyst to catalyze this multi-component reaction for aliphatic amines and aliphatic aldehydes. Next, ethylamine as an aliphatic amine and butyraldehyde and heptanal as aliphatic aldehydes were used to investigate the potential of BaSO SB 4 sb in promoting the reaction for aliphatic substrates. [Extracted from the article]

Autosomal recessive cerebellar ataxias are a group of heterogeneous early‐onset progressive disorders that some of them are treatable. We performed a 4‐year follow‐up for 25 patients who had treatable ataxia. According to our study, patients would benefit from early detection of treatable ataxia, close observation, and follow‐up. [ABSTRACT FROM AUTHOR]

• A new set of imidazole derivatives were synthesized and characterized. • The synthesized compounds (7a-f) were screened for their in vitro antifungal activities against several fungal strains. • Compounds 7c, 7d and 7f exhibited excellent activities against tested fungi species with MIC 90 values in the range of 0.5-16 µg/ml. • Molecular modelling studies and molecular dynamic simulation were carried out to predict the possible interaction mode of these compounds in the binding site of lanosterol 14α-demethylase (CYP51). • These compounds can be considered as antifungal candidates for further development. Fungal infections have become a serious threat to human health due to their high incidence and mortality. In this study, a new set of imidazole derivatives (7a-f) were synthesized and their chemical structures were characterized using spectroscopic techniques including IR, 1H-NMR, 13C-NMR and Mass. In the following, the antifungal activities of these derivatives were evaluated against several yeasts, aspergillus and dermatophyte species using the CLSI method. In addition, to check the safety of the synthesized compounds, the in vitro cytotoxicity activity of these compounds was investigated towards normal human fibroblasts cell line (MRC-5) using MTT assay. The obtained biological results indicated that these compounds acted as the most potential antifungal agents. In particular, compounds 7c, 7d and 7f exhibited excellent activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, Candida dubliniensis, Candida parapsilosis , and Cryptococcus neoformans species with MIC 50 values in the range of 0.5-16 µg/ml. The cytotoxicity results showed that these compounds have low toxicity against normal human fibroblasts cell line (MRC-5). Additionally, molecular modelling studies and molecular dynamic simulation were carried out to predict the binding energy and possible interaction mode of these compounds in the binding site of lanosterol 14α-demethylase (CYP51) as a conventional target for azole derivatives. In silico ADME study was also performed to investigate the physicochemical features of the synthesized imidazole derivatives. According to the results, these compounds can be considered as promising antifungal candidates for further development. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of imidazole bearing different substituted thioquinolines were synthesized as α-glucosidase inhibitors. • All derivatives exhibited significantly better potency (IC 50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose. • In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. • 8g reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC 50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC 50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with K i = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health. [ABSTRACT FROM AUTHOR]

In this study, benzidine (BnZ) is used not only as a reducing agent but also as the spacer on the supercapacitive behavior of the synthesized graphene nanocomposite film. The synthesized graphene nanocomposite was examined by crystalline size, structural morphology, presence of functional groups to X‐ray diffraction, scanning electron microscope, and Fourier transform infrared spectroscopy. Furthermore, chemical composition moieties are evidenced by X‐ray photoelectron spectroscopy. Poly ortho aminophenol as a p‐type conductive polymer was introduced into the channels of Bnz‐rGOAerogel. This composite structure with a high surface area and pore volume can effectively play a synergistic role between the two materials, thus improving its overall performance. In addition, the specific capacitance of the prepared spherical composite electrode is as high as 625 F/g at 1.0 A/g current density, and the retention rate of the initial capacity is 89% after 3,000 cycles in acidic solution, which has good cycle stability. [ABSTRACT FROM AUTHOR]

In order to show antiproliferation and cancerous cell growth inhibition of quinazoline derivatives, a series of 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones (H1–H11) were synthesized. In vitro cytotoxic activities were evaluated against three human cancer cell lines: A549, MCF-7 and SW1116 using colorimetric MTT assay. Comparing their effects together and with cisplatin as a positive control indicated that H3, H5 and H6 exhibited better antitumor activities on A549 cell line with IC50 values less than 10 μM versus 12 μM for cisplatin. In the case of MCF-7 and SW1116 cell lines, almost all compounds displayed better cytotoxic activities than cisplatin. Molecular docking studies were applied on epidermal growth factor receptor (EGFR) as the main target of quinazoline scaffolds in cancer therapy to predict the binding energies, binding modes and orientation of these ligands toward the active site of the receptor. In silico physicochemical parameters and ADMET profiling calculations also were done. All compounds showed lower binding energies than erlotinib, the inhibitor of EGFR. Taken together, our findings showed potential anticancer effect of quinazoline compounds bearing various phenyl ring substitutions. [ABSTRACT FROM AUTHOR]

• A novel series of carbazole-benzylpiperazine hybrids were synthesized and characterized. • The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the synthesized compounds were evaluated. • Compounds 7a, 7e and 7k were identified as the most promising candidate for further study. • This work is helpful for researchers who planning to design and develop AChE and BuChE inhibitors. A novel series of carbazole-benzylpiperazine hybrids (7a–n) were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated. The biological results indicated that the nature of linker between carbazole and benzylpiperazine moieties as well as the type of substitutions on the phenyl ring of benzylpiperazine moiety greatly affected the inhibitory activity and selectivity of the synthesized compounds towards eelAChE and eqBuChE enzymes. Among all the synthesized compounds, compounds 7a (IC 50 = 8.9 µM) and 7e (IC 50 = 5.7 µM) with fluorine substitution at meta and para positions of the phenyl ring showed the highest inhibitory activity against eelAChE and maximum inhibitory activity against eqBuChE were generated by compounds 7h (IC 50 = 5.4 µM) and 7k (IC 50 = 4.5 µM) with fluorine and methyl substitutions at meta position of the phenyl ring, respectively. Furthermore, kinetic analysis and molecular modeling studies revealed that the most active compound 7e acts as a mixed-type inhibitor against AChE, which suggested this compound interacted with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE enzyme. [Display omitted] [ABSTRACT FROM AUTHOR]