TRX/TXNIP/miRs network in neuronal cells and TXNIP-targeted miRs modulate neuroinflammation, neuronal apoptosis, and mitochondrial dysfunction in Parkinson's disease: A review.

The purpose of this review is to explore the role of the thioredoxin (TRX)/TRX-interacting protein (TXNIP)/microRNAs (miRs) network in neuronal cells and the function of TXNIP-targeted miRs in regulating neuroinflammation, neuronal apoptosis, and mitochondria dysfunction in Parkinson's disease (PD). The high TXNIP level activates apoptosis signal-regulating kinase-1 (ASK-1) and trigger a signaling cascade involving the phosphorylation of c-Jun-N-terminal kinase (JNK) and mitogen-activated protein kinase (p38 MAPK). The activation of these kinases contributes to the misfolding and aggregation of α-synuclein, a hallmark of PD.

Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel K3.1.

The 1,4-dihydropyridines, drugs with well-established bioavailability and toxicity profiles, have proven efficacy in treating human hypertension, peripheral vascular disorders, and coronary artery disease. Every 1,4-dihydropyridine in clinical use blocks L-type voltage-gated calcium channels. We now report our development, using selective optimization of a side activity (SOSA), of a class of 1,4-dihydropyridines that selectively and potently inhibit the intermediate-conductance calcium-activated K channel K3.

Nexus of NFκB/VEGF/MMP9 signaling in diabetic retinopathy-linked dementia: Management by phenolic acid-enabled nanotherapeutics.

Aims: The purpose of this review is to highlight the therapeutic effectiveness of phenolic acids in slowing the progression of diabetic retinopathy (DR)-linked dementia by addressing the nuclear factor kappa B (NFκB)/matrix metalloproteinase-9 (MMP9)/vascular endothelial growth factor (VEGF) interconnected pathway.

Materials And Methods: We searched 80 papers published in the last 20 years using terms like DR, dementia, phenolic acids, NFkB/VEFG/MMP9 signaling, and microRNAs (miRs) in databases including Pub-Med, WOS, and Google Scholar. By encasing phenolic acid in nanoparticles and then controlling its release into the targeted tissues, nanotherapeutics can increase their effectiveness.

Participation of Lens Proteins and miRs in Traumatic and Inheritance Cataract: A Review on Diagnostic and Therapeutic Approaches for Cataract Management.

Traumatic and inherited cataract spiking blindness is caused by accumulated deposition of mutant eye lens protein or lens microarchitecture alteration. A traumatic cataract is a clouding of the eye's natural lens that occurs as a result of physical trauma to the eye. This trauma can be caused by various incidents such as blunt force injury, penetration by a foreign object, or a significant impact on the eye area.

The Dysregulated MAD in Mad: A Neuro-theranostic Approach Through the Induction of Autophagic Biomarkers LC3B-II and ATG.

The word mad has historically been associated with the psyche, emotions, and abnormal behavior. Dementia is a common symptom among psychiatric disorders or mad (schizophrenia, depression, bipolar disorder) patients. Autophagy/mitophagy is a protective mechanism used by cells to get rid of dysfunctional cellular organelles or mitochondria.

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) causes seizure activity in larval zebrafish via antagonism of γ-aminobutyric acid type A receptor α1β2γ2.

Hexahydro-1,3,5-trinitro-1,3,5-triazine, or Royal Demolition Explosive (RDX), is a major component of plastic explosives such as C-4. Acute exposures from intentional or accidental ingestion are a documented clinical concern, especially among young male U.S.

Computational design of peptides to target Na1.7 channel with high potency and selectivity for the treatment of pain.

The voltage-gated sodium Na1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human Na1.

A metasurface-based electronically steerable compact antenna system with reconfigurable artificial magnetic conductor reflector elements.

Beyond 5G networks would require newer technologies to deliver a smarter network. In accordance with these requirements, an electronically steerable compact antenna system capable of beam-switching in the azimuth plane is proposed. The design uses a monopole antenna as the main radiator surrounded by metasurface-based electronically reconfigurable reflector elements designed for the sub-6GHz range.

Riluzole and novel naphthalenyl substituted aminothiazole derivatives prevent acute neural excitotoxic injury in a rat model of temporal lobe epilepsy.

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration.

Identification of a TNF-TNFR-like system in malaria vectors (Anopheles stephensi) likely to influence Plasmodium resistance.

Identification of Plasmodium-resistance genes in malaria vectors remains an elusive goal despite the recent availability of high-quality genomes of several mosquito vectors. Anopheles stephensi, with its three distinctly-identifiable forms at the egg stage, correlating with varying vector competence, offers an ideal species to discover functional mosquito genes implicated in Plasmodium resistance. Recently, the genomes of several strains of An.

A Randomized Controlled Trial of Intravenous Scopolamine Versus Active-Placebo Glycopyrrolate in Patients With Major Depressive Disorder.

To investigate scopolamine's rapid-acting antidepressant effects using an active placebo comparator. Most prior intravenous scopolamine studies reduced depressive symptomatologies compared to saline placebo infusions within 3 days. However, the confounding effect of placebo is unknown given that only saline placebo has been used in prior studies.

Integrating Genetic Structural Variations and Whole-Genome Sequencing Into Clinical Neurology.

Advances in genome sequencing technologies have unlocked new possibilities in identifying disease-associated and causative genetic markers, which may in turn enhance disease diagnosis and improve prognostication and management strategies. With the capability of examining genetic variations ranging from single-nucleotide mutations to large structural variants, whole-genome sequencing (WGS) is an increasingly adopted approach to dissect the complex genetic architecture of neurologic diseases. There is emerging evidence for different structural variants and their roles in major neurologic and neurodevelopmental diseases.

GM1 ganglioside modifies microglial and neuroinflammatory responses to α-synuclein in the rat AAV-A53T α-synuclein model of Parkinson's disease.

Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side compared to the non-injected (control) side.

An Integrative Multi-Omics Analysis Reveals MicroRNA-143 as a Potential Therapeutic to Attenuate Retinal Angiogenesis.

Retinal neovascularization is a severe complication of proliferative diabetic retinopathy (PDR). MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. In this study, we show that miR-143-3p is significantly downregulated in the retina of a rat model of oxygen-induced retinopathy (OIR) by miRNA-sequencing.

The seizure-inducing plastic explosive RDX inhibits the α1β2γ2 GABA receptor.

Objective: Royal demolition explosive (RDX) can induce seizures in wildlife and humans following release into the environment or after voluntary consumption. During the Vietnam War, RDX intoxication was the most common cause of generalized seizures in US service personnel, and in some sections of the armed forces, eating of RDX has continued as "a dare" to this day. After its mechanism of action was long unknown, RDX was recently shown to be a GABA receptor antagonist.

Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities.

The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis.

Cryptography in Hierarchical Coded Caching: System Model and Cost Analysis.

The idea behind network caching is to reduce network traffic during peak hours via transmitting frequently-requested content items to end users during off-peak hours. However, due to limited cache sizes and unpredictable access patterns, this might not totally eliminate the need for data transmission during peak hours. Coded caching was introduced to further reduce the peak hour traffic.

Artificial Intelligence-Based Portable Bioelectronics Platform for SARS-CoV-2 Diagnosis with Multi-nucleotide Probe Assay for Clinical Decisions.

In the context of the recent pandemic, the necessity of inexpensive and easily accessible rapid-test kits is well understood and need not be stressed further. In light of this, we report a multi-nucleotide probe-based diagnosis of SARS-CoV-2 using a bioelectronics platform, comprising low-cost chemiresistive biochips, a portable electronic readout, and an Android application for data acquisition with machine-learning-based decision making. The platform performs the desired diagnosis from standard nasopharyngeal and/or oral swabs (both on extracted and non-extracted RNA samples) without amplifying the viral load.

Towards point-of-care diagnosis of Alzheimer's disease: Multi-analyte based portable chemiresistive platform for simultaneous detection of β-amyloid (1-40) and (1-42) in plasma.

Label-free simultaneous detection of Alzheimer's disease (AD) specific biomarkers Aβ40 and Aβ42 peptides on a single platform using polypyrrole nanoparticle-based chemiresistive biosensors is reported here. The proposed interdigitated-microelectrode based inexpensive multisensor-platform can concurrently detect Aβ40 and Aβ42 in spiked-plasma in the range of 10 - 10 g/mL (with LoDs being 5.71 and 9.

Novel wideband circularly polarized DRA with squint-free radiation characteristics.

A new single-fed circularly polarized dielectric resonator antenna (CP-DRA) without beam squint is presented. The DRA comprises an S-shaped dielectric resonator (SDR) with a metalized edge and two rectangular dielectric resonators (RDRs) blocks. Horizontal extension section is applied as an extension of the SDR, and a vertical-section is placed in parallel to the metallic edge.

Investigation of NH3 as a selective thyroid hormone receptor modulator in larval zebrafish (Danio rerio).

Thyroid hormones (THs) are essential for normal vertebrate development and diverse environmental chemicals are hypothesized to cause developmental toxicity by disrupting TH-mediated signaling. The larval zebrafish (Danio rerio) is an emerging in vivo model of developmental TH disruption; however, the effects of TR antagonism have not yet been studied in zebrafish. NH3, generally considered a potent and specific thyroid hormone receptor (TR) antagonist, has been used in rodents and Xenopus laevis to characterize phenotypes of TR antagonism.

A facile, sensitive and rapid sensing platform based on CoZnO for detection of fipronil; an environmental toxin.

A sensitive detection of extremely toxic phenylpyrazole insecticide, 'Fipronil' is presented. Currently, the advancement of approaches for the detection of insecticides at low concentrations with less time is important for environmental safety assurance. Considering this fact, an effort has been made to develop an electrospun CoZnO nanofiber (NF) based label-free electrochemical system for the detection of fipronil.