Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

The potential protective effect of aqueous extract of Acanthophyllum glandulosum root on Streptozotocin-induced diabetes in mice.

Purpose: Treatment of diabetes using traditional medicine has attracted attention in recent decades because of its unique benefits. Acanthophyllum glandulosum is known as an herb with therapeutic potential. This research explored the likely protective effects of Acanthophyllum Glandulosum Root (AGR) in mice with Streptozotocin-induced type 2 diabetes mellitus (T2DM) to provide complementary therapy. Methods: Diabetes was induced by a single injection of Streptozotocin (STZ) in mice. STZ-diabetic mice were treated with oral dosages of AGR (25, 50, 100, and 200 mg/kg) on different experiment days. During the experiment, the effect of a topical extract of AGR on Glucose level, serum lipid profile, and liver and kidney biomarkers, with the histopathological assessment of heart, kidney, spleen, and liver, were investigated. The gene expression level of inflammation biomarkers (Tumour Necrosis Factor-alpha (TNF-α) and interleukin-1 (IL-1)), apoptosis factor (Caspase3), glucose regulatory genes (Glucose transporter (GLUT) 4 and 2), and lipid regulatory gene (Adenosine 50-monophosphate protein-kinase (AMPK)) were investigated. Results: Administration of AGR to STZ-diabetic mice decreased blood glucose level (p < 0.01), normalized the lipid profile (p < 0.01), improved the serum level of kidney (p < 0.01) and liver biomarkers (p < 0.01), and normalized Kidney hypertrophy (p < 0.01), inflammation (p < 0.001), and apoptosis (p < 0.01). The AGR effect was better at 100 mg/kg than Metformin (100 mg/kg) on healing T2DM condition in mice. Conclusion: AGR possesses anti-inflammatory, antioxidant, anti-hyperglycemic, anti-hyperlipidemic, and anti-glycation activity, thus exhibiting a protective function in STZ-induced diabetic mice. Further in vitro and in vivo works are necessary, especially to elucidate the mechanism of action of AGR at the cellular and molecular levels.

Advances in RNAi therapies for gastric cancer: Targeting drug resistance and nanoscale delivery.

Gastric cancer poses a significant health challenge, and exploring innovative therapeutic strategies is imperative. RNA interference (RNAi) has employed as an important therapeutic strategy for diseases by selectively targeting key pathways involved in diseases pathogenesis. Small interfering RNA (siRNA), a potent RNAi tool, possesses the capability to silence genes and downregulate their expression. This review provides a comprehensive examination of the potential applications of small interfering RNA (siRNA) and short hairpin RNA (shRNA), supplemented by an in-depth analysis of nanoscale delivery systems, in the context of gastric cancer treatment. The potential of siRNA to markedly diminish the proliferation and invasion of gastric cancer cells through the modulation of critical molecular pathways, including PI3K, Akt, and EMT, is highlighted. Besides, siRNA demonstrates its efficacy in inducing chemosensitivity in gastric tumor cells, thus impeding tumor progression. However, the translational potential of unmodified siRNA faces challenges, particularly in vivo and during clinical trials. To address this, we underscore the pivotal role of nanostructures in facilitating the delivery of siRNA to gastric cancer cells, effectively suppressing their progression and enhancing gene silencing efficiency. These siRNA-loaded nanoparticles exhibit robust internalization into gastric cancer cells, showcasing their potential to significantly reduce tumor progression. The translation of these findings into clinical trials holds promise for advancing the treatment of gastric cancer patients.

Neural-network decoders for measurement induced phase transitions.

Open quantum systems have been shown to host a plethora of exotic dynamical phases. Measurement-induced entanglement phase transitions in monitored quantum systems are a striking example of this phenomena. However, naive realizations of such phase transitions requires an exponential number of repetitions of the experiment which is practically unfeasible on large systems. Recently, it has been proposed that these phase transitions can be probed locally via entangling reference qubits and studying their purification dynamics. In this work, we leverage modern machine learning tools to devise a neural network decoder to determine the state of the reference qubits conditioned on the measurement outcomes. We show that the entanglement phase transition manifests itself as a stark change in the learnability of the decoder function. We study the complexity and scalability of this approach in both Clifford and Haar random circuits and discuss how it can be utilized to detect entanglement phase transitions in generic experiments.

Analysis of NFKB1 and NFKB2 gene expression in the blood of patients with sudden sensorineural hearing loss.

OBJECTIVES: Sudden Sensorineural Hearing Loss (SSNHL) is an increasingly common health problem today. Although the direct mortality rate of this disorder is relatively low, its impact on quality of life is enormous; this is why accurate identification of pathogenesis and influencing factors in the disease process can play an essential role in preventing and treating the disease. Acute inflammation, which leads to chronic inflammation due to aberrant expression of inflammation-mediating genes, may play a significant role in the pathogenesis of the disease. The essential Nuclear factor kappa B (NF-kB) pathway genes, NFKB1 and NFKB2, serve as prothrombotic agents when expressed abnormally, compromising the cochlea by disrupting the endolymphatic potential and causing SSNHL. METHODS: This study investigates the expression levels of NFKB1 and NFKB2 in peripheral blood (PB) through a quantitative polymerase chain reaction in 50 Iranian patients with SSNHL, and 50 healthy volunteers were of the same age and sex as controls. RESULTS: As a result, NFKB2 expression levels in patients were higher than in controls, regardless of sex or age (posterior beta = 0.619, adjusted P-value = 0.016), and NFKB1 expression levels did not show significant differences between patients and controls. The expression levels of NFKB1 and NFKB2 had significantly strong positive correlations in both SSNHL patients and healthy individuals (r = 0.620, P = 0.001 and r = 0.657, P 0.001, respectively), suggesting the presence of an interconnected network. CONCLUSION: NFKB2 has been identified as a significant inflammatory factor in the pathophysiology of SSNHL disease. Inflammation can play an essential role in developing SSNHL, and our findings could be used as a guide for future research.

In vitro biocompatibility evaluations of pH-sensitive Bi2MoO6/NH2-GO conjugated polyethylene glycol for release of daunorubicin in cancer therapy.

Here, a pH-sensitive biocompatible nanocarrier system is synthesized by the combination of Bi2MoO6 nanoparticles, NH2-graphene oxide (GO), and polyethylene glycol (PEG) for loading and delivery of daunorubicin (DNR) into breast cancer cells. DNR is loaded onto the nanocarrier surface via covalent bonding, exhibiting pH-sensitive behavior so that in acidic pH, nearly 86.85% of the drug is released, but in biological pH, only about 15% of the drug is released. The resulting Bi2MoO6/NH2-GO/PEG/DNR has a high drug loading content (33.29%) and encapsulation efficiency (99.75%). By examining the toxicity of the nanocarrier-loaded drug, no adverse effect is observed on healthy cells HUVEC, and the survival rate of cancer cells MCF-7 decreases with increasing the nanocarrier concentration. Moreover, the free drug is found to be more toxic than DNR attached to the nanocarrier. The complement activation (C3 and C4 levels), prothrombin time and activated partial thromboplastin time analyses also indicate its excellent blood compatibility. The hemolysis analysis (HRs),used to evaluate the nanocarrier compatibility. the results show that even in high concentrations(5-100 µg/ml), the percentage of hemolysis is below 1.8%, which indicates that the nanocarrier is safe to blood cells. These results evidence the therapeutic nature of the biocompatible Bi2MoO6/NH2-GO/PEG, proposing it as an efficient anticancer nanocarrier for drug delivery and other biomedical application purposes.

Assessing the expression of two post-transcriptional BDNF regulators, TTP and miR-16 in the peripheral blood of patients with Schizophrenia.

Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjusted P-value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls (r = 0.701, P < 0.001 and r = 0.777, P < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ.

Kinematic and mechanical modelling of a novel 4-DOF robotic needle guide for MRI-guided prostate intervention.

Traditionally ultrasound-guided biopsy has been used to diagnose prostate cancer despite of its poor soft tissue contrast and frequent false negative results. Magnetic Resonance Imaging (MRI) has the advantage of excellent soft tissue contrast for guiding and monitoring prostate biopsy. However, its working area and access in the confined MRI bore space limit the use of interventional guide devices including robotic systems. To provide robotic precision, greater access, and compact design, we designed a novel robotic mechanism that can provide four degrees of freedom (DOF) manipulation in a compact form comparable to size of manual templates. To develop the mechanism, we established a mathematical model of inverse and forward kinematics and prototyped a proof-of-concept needle guide for MRI guided prostate biopsy. The mechanism was materialized using four discs that house small passive spherical joints that can be moved by rotating the discs consisting of grooved profile. With an initial needle insertion angle range of ±15°, we identified mathematical and kinematic parameters for the mechanism design and fabricated the first prototype that has dimension of 40 × 110 × 180 mm3. The prototype demonstrated that the unique robotic manipulation can physically be delivered and could provide precise needle guidance including angulated needle insertion with higher structural rigidity.

Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review.

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is one of the most common neurodegenerative diseases worldwide. MS results in serious neurological dysfunctions and disability. Disturbances in coding and non-coding genes are key components leading to neurodegeneration along with environmental factors. Long non-coding RNAs (lncRNAs) are long molecules in cells that take part in the regulation of gene expression. Several studies have confirmed the role of lncRNAs in neurodegenerative diseases such as MS. In the current study, we performed a systematic analysis of the role of lncRNAs in this disorder. In total, 53 studies were recognized as eligible for this systematic review. Of the listed lncRNAs, 52 lncRNAs were upregulated, 37 lncRNAs were downregulated, and 11 lncRNAs had no significant expression difference in MS patients compared with controls. We also summarized some of the mechanisms of lncRNA functions in MS. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms. Evaluation of their diagnostic significance and therapeutic potential could help in the design of novel treatments for MS.

Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the "JAK-STAT signaling pathway" and "Adipocytokine signaling pathway." An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

Entanglement Entropy Scaling Transition under Competing Monitoring Protocols.

Dissipation generally leads to the decoherence of a quantum state. In contrast, numerous recent proposals have illustrated that dissipation can also be tailored to stabilize many-body entangled quantum states. While the focus of these works has been primarily on engineering the nonequilibrium steady state, we investigate the buildup of entanglement in the quantum trajectories. Specifically, we analyze the competition between two different dissipation channels arising from two incompatible continuous monitoring protocols. The first protocol locks the phase of neighboring sites upon registering a quantum jump, thereby generating a long-range entanglement through the system, while the second destroys the coherence via a dephasing mechanism. By studying the unraveling of stochastic quantum trajectories associated with the continuous monitoring protocols, we present a transition for the scaling of the averaged trajectory entanglement entropies, from critical scaling to area-law behavior. Our work provides an alternative perspective on the measurement-induced phase transition: the measurement can be viewed as monitoring and registering quantum jumps, offering an intriguing extension of these phase transitions through the long-established realm of quantum optics.

Apoptotic Genes of Bax, Bad, Bcl2, and P53 in A549 Lung Cancer Cells Comparison of the Effect of Echinophora platyloba DC. Extract and Cordia myxa L Extract on the Expression of Apoptotic Genes of Bax, Bad, Bcl2, and P53 in A549 Lung Cancer Cells.

INTRODUCTION: Lung cancer is the most deadly and sumptuous cancer across the globe. Cancer occurrence is increasing progressively and there is no ideal cure yet. Therefore, new therapeutic areas are needed. The use of herbal extracts due to its properties such as antioxidant activity, anti-proliferative effect, and few side effects can be promising in the treatment of cancer. This study aimed to compare the effect of Echinophora platyloba DC. and Cordia myxa L extracts on apoptosis induction in A549 cancer cells. MATERIALS AND METHODS: In this experiment, the A549 cell line was first cultured in DMEM medium containing 10% FBS and then treated with different concentrations of both compounds. MTT assay was performed to determine IC50 and to compare the viability of cells treated with different concentrations of Echinophora platyloba DC. and Cordia myxa L seed on days 1, 3 and 5. QRT-PCR test was used to investigate the effects of Echinophora platyloba DC. and Cordia myxa L with IC50 on apoptosis induction. RESULTS: MTT results showed that both plant extracts resulted in cell death and decreased viability of lung cancer cells. But the percentage of viability decreased by Echinophora platyloba DC. was more. Also, Echinophora platyloba DC. significantly increased the expression of Bax, P53 and Bad apoptotic genes and decreased the expression of Bcl2 gene, which induces apoptotic death and the cytotoxic effect of Echinophora platyloba DC. over Cordia myxa L. CONCLUSION: In comparing the effects of these two extracts Echinophora platyloba DC. was more effective than Cordia myxa L and had greater cytotoxicity on A549 cancerous cells in a lesser concentration and could be an appropriate drug candidate for the treatment of lung cancer.

Many-Body Chern Number from Statistical Correlations of Randomized Measurements.

One of the main topological invariants that characterizes several topologically ordered phases is the many-body Chern number (MBCN). Paradigmatic examples include several fractional quantum Hall phases, which are expected to be realized in different atomic and photonic quantum platforms in the near future. Experimental measurement and numerical computation of this invariant are conventionally based on the linear-response techniques that require having access to a family of states, as a function of an external parameter, which is not suitable for many quantum simulators. Here, we propose an ancilla-free experimental scheme for the measurement of this invariant, without requiring any knowledge of the Hamiltonian. Specifically, we use the statistical correlations of randomized measurements to infer the MBCN of a wave function. Remarkably, our results apply to disklike geometries that are more amenable to current quantum simulator architectures.

An Optimization-Based Algorithm for Trajectory Planning of an Under-Actuated Robotic Arm to Perform Autonomous Suturing.

In single-port access surgeries, robot size is crucial due to the limited workspace. Thus, a robot may be designed under-actuated. Suturing, in contrast, is a complicated task and requires full actuation. This study aims to overcome this shortcoming by implementing an optimization-based algorithm for autonomous suturing for an under-actuated robot. The proposed algorithm approximates the ideal suturing trajectory by slightly reorienting the needle while deviating as little as possible from the ideal, full degree-of-freedom suturing case. The deviation of the path taken by a custom robot with respect to the ideal trajectory varies depending on the suturing starting location within the workspace as well as the needle size. A quantitative analysis reveals that in 13% of the investigated workspace, the accumulative deviation was less than 10 mm. In the remaining workspace, the accumulative deviation was less than 30 mm. Likewise, the accumulative deviation of a needle with a radius of 10 mm was 2.2 mm as opposed to 8 mm when the radius was 20 mm. The optimization-based algorithm maximized the accuracy of a four-DOF robot to perform a path-constrained trajectory and illustrates the accuracy-workspace correlation.

A new electrochemical sensing platform based on HgS/graphene composite deposited on the glassy carbon electrode for selective and sensitive determination of propranolol.

Fabrication of selective, sensitive and reliable sensing platform for detection of propranolol (PRO) is still a great challenge. In this study, a new sensitive and selective electrochemical sensor was fabricated for the electrochemical determination of PRO using HgS/graphene composite. The incorporation of HgS microstructures on graphene sheets was done via a facile one-step method, where the simultaneous reduction of GO and the in-situ generation of HgS happened. Owing to the large surface area, excellent electronic conductivity and more electro-active sites provided by graphene, the HgS/graphene composite exhibited better electrochemical ability through the detection of PRO compared to the bare HgS. The HgS/graphene sensor revealed superb selectivity, good repeatability and superior stability of about 96.0 % of its original response after five weeks. Moreover, the sensor displayed excellent analytical parameters such as linear range of 0.5-50.0 µM with low detection limit of 0.05 µM (S/N = 3) and good sensitivity (0.1851 µA/µM). Furthermore, the constructed sensor was applied for detection of PRO in real and pharmaceutical samples, with good recoveries, ranging from 96.0 to 102.0%. The HgS/graphene composite provided here displayed satisfactory electrochemical features may hold great potential to the improvement of electrochemical sensors and electronic devices.

Design and characterization of a novel pH-sensitive biocompatible and multifunctional nanocarrier for in vitro paclitaxel release.

Breast cancer is one of the main reasons of women's mortality. A novel ternary combination of ZnAl-layered double hydroxides (LDH), cobalt ferrite (CoFe2O4) and N-graphene quantum dots (N-GQDs) proposes a pH-sensitive multifunctional nanocomposite that can improve therapeutic features of each compound; this is a notable strategy to make biocompatible materials with unique properties for paclitaxel (PTX) delivery in breast cancer cells. For proving the surface modification process of materials, electrochemical techniques including cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were carried out. By coating PEG on the surface of the N-GQDs/CoFe2O4/LDH, it developed a drug delivery system with low toxicity, an excellent encapsulation efficiency 88.4%, drug loading capacity of ca. 31%, and slow and sustained release behavior (9% after 72 h) under normal physiological conditions. Besides, a high drug release (~69%) at low-pH as a model of the extracellular tumor environment indicated a pH-sensitive release behavior. Moreover, cell viability assay proved the negligible cytotoxicity on normal cells (L929) and the improved growth inhibition effect of PTX/N-GQDs/CoFe2O4/LDH nanocarrier on MCF7 cancer cells. Blood compatibility test values with respect to red blood cell aggregation (RBC), coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) remained within normal ranges without toxicity effect on RBCs and complement factors. Overall, this novel designed PTX/N-GQDs/CoFe2O4/LDH nanocarrier with tremendously biocompatible, slow-release and pH-dependent features could be considered as a theranostic candidate for various anticancer drugs delivery and cancer therapy.

A biocompatible nanoplatform formed by MgAl-layered double hydroxide modified Mn3O4/N-graphene quantum dot conjugated-polyaniline for pH-triggered release of doxorubicin.

In this work, for the first time, a novel pH-sensitive biocompatible multifunctional nanocarrier was fabricated by the combination of MgAl-layered double hydroxide, Mn3O4 nanoparticles, N-graphene quantum dot and polyaniline (PANI/N-GQD/MO/LDH) for doxorubicin (DOX) delivery in breast cancer cells. Electrochemical techniques, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), were employed for proving the surface modification process. The integration of polyaniline on the surface of the nanocarrier provides ultrahigh DOX encapsulation up to 90% and possesses a slow-release behavior (4% after 72 h) under normal physiological conditions. However, releasing ~80% of the drug in a low-pH environment as a model of the extracellular tumor environment happened, presenting a pH-triggered release. The cell viability using MTT assay reveals that the DOX/PANI/N-GQD/MO/LDH had no apparent adverse effect on the viability of human L929 normal cells. Furthermore, a significant inhibition ratio against human breast cancer cell lines (MCF-7) was observed when the cells were treated with the DOX-loaded PANI/N-GQD/MO/LDH nanocarrier, suggesting that this nanocarrier could increase the therapeutic efficacy of DOX. The hemolysis rates (HRs) of human fresh blood, coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) revealed the excellent blood compatibility of the nanocarrier. Thus, the nano-vehicle designed in this study could be used as a novel multifunctional and synergistic, pH-triggered platform for delivering various anti-cancer drugs and other biomedical applications.

A novel selective ternary platform fabricated with MgAl-layered double hydroxide/NiMn2O4 functionalized polyaniline nanocomposite deposited on a glassy carbon electrode for electrochemical sensing of levodopa.

In this study, a novel selective electrochemical sensor was fabricated for determination of levodopa (LD) using a glassy carbon electrode modified with MgAl-layered double hydroxide/NiMn2O4 functionalized polyaniline nanocomposite (LDH/NMO/PANI) and its successful formation was confirmed by various techniques. Owing to the high surface area and outstanding conductivity features provided by the combination of MgAl-LDH, NiMn2O4 and PANI nanoparticles, this ternary nanocomposite exhibited excellent electrochemical activity towards the detection of LD compared with the electrode modified by the pristine MgAl-LDH and MgAl-LDH/NiMn2O4 binary nanocomposite. In addition, enormous quantities of amine and imine functional groups on the surface of PANI lead to a strong affinity for attachment to organic molecules such as LD. The ternary nanocomposite modified electrode exhibited excellent analytical parameters such as wide linear response from 0.1 to 100 µM with very low detection limit of 0.005 µM, good reproducibility and long-term stability which are superior among the LD electrochemical sensors. Besides, the constructive sensor possessed acceptable selectivity for recognition of LD in the presence of a variety of potentially interfering species and can also effectively avoid the interference of dopamine (DA) and ascorbic acid (AA). Consequently, the LDH/NMO/PANI/GC electrode was effectively applied to detect LD in human plasma and urine samples with good recoveries, ranging from 98.0-100.1% and it shows potential usage in clinical researches.

A high-sensitive electrochemical DNA biosensor based on a novel ZnAl/layered double hydroxide modified cobalt ferrite-graphene oxide nanocomposite electrophoretically deposited onto FTO substrate for electroanalytical studies of etoposide.

The combination of layered double hydroxides (LDHs), cobalt ferrite (CoFe2O4) and graphene oxide (GO) creates a ternary nanocomposite that can incredibly improve advantages of each compound; this is an impressive way to attain multifunctional materials with attractive properties. In this study, a new high-sensitive electrochemical DNA biosensor was fabricated for the electroanalytical studies of etoposide using a novel ZnAl/layered double hydroxide modified cobalt ferrite-graphene oxide nanocomposite (GO/CoFe2O4/ZnAl-LDH) that was electrophoretically deposited (EPD) on the fluorine tin oxide (FTO) substrate. This DNA biosensor was prepared via electrostatic adsorption of DNA onto the GO/CoFe2O4/ZnAl-LDH/FTO electrode. The electrochemical behavior of electrodes was characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). EIS plot obviously demonstrated a rapid electron transport at low frequencies for GO/CoFe2O4/ZnAl-LDH. Differential pulse voltammetry (DPV) and square wave anodic stripping voltammetry (SWASV) were employed for the electrochemical detection of ETO. The results revealed that DNA/GO/CoFe2O4/ZnAl-LDH/FTO bioelectrode had ultrahigh sensitivity to ETO with the detection limit of 0.0010 µM in the linear range of 0.2-10 µM. In addition, the developed biosensor revealed precise reproducibility and excellent stability of about 95% of the initial activity after 6-7 weeks. On the other hand, the present bioelectrode was also capable of discriminating different interferences and was also used to detect etoposide in real samples such as human blood plasma, serum and urine with good recoveries, ranging from 97.0% to 104.0%. The obtained results of the excellent performance of this biosensor could be assigned to the active reaction sites and good electrochemical activity of nanocomposites, hence helping increase the DNA immobilization and accelerate the electron transfer more effectively on the surface electrode.

Genetics of intellectual disability in consanguineous families.

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.