Access to Branched 1,3-Dienes Innate C(sp)-H Functionalization of 8-Methylquinolines.

Allenes have gained prominence in transition metal-catalyzed C-H activation reactions due to their versatile reactivity. While C(sp)-H functionalization with allenes has been well explored, the functionalization of more challenging C(sp)-H bonds with allenes remains largely underexplored. Herein, we present a scalable Rh(III)-catalyzed strategy for the site-selective C(sp)-H dienylation of biologically relevant 8-methylquinolines employing allenyl carbinol acetates for accessing structurally diverse 1,3-dienes.

Kyasanur Forest Disease Virus: Epidemiological Insights, Pathogenesis, Therapeutic Strategies, and Advances in Vaccines and Diagnostics.

Kyasanur Forest disease virus (KFDV), a tick-borne Orthoflavivirus endemic to the Indian subcontinent, is a public health threat due to its recurrent outbreaks and expanding geographic range. This review provides a comprehensive overview of KFDV, encompassing its epidemiological trends, transmission dynamics, and ecological determinants that influence its spread. We delve into the current understanding of KFDV pathogenesis, highlighting key viral and host factors that drive infection and disease progression.

Photomechanical B←N Molecular Crystals: From Single-Crystal-to-Single-Crystal [2 + 2] Photodimerization to Polymerization.

ConspectusOrganoboron-based crystalline compounds, which can respond to external stimuli (heat, light, electric field, or pressure), have already emerged as smart materials with well-directed functions. While various weak noncovalent interactions remain key to the supramolecular design, the exploitation of relatively strong boron-nitrogen dative bonds (B←N bonds) in constructing functional crystalline molecular and polymeric assemblies has recently attracted significant research interest. In particular, the strategic incorporation of B←N bonds into stimuli-responsive crystalline materials is promptly shaping a new direction in the field.

Contribution of Nonaxial n → σ* Orbital Interactions in Tetrel Bonding: A Case Study on Si…N Interactions.

The formation of a σ-hole interaction is typically associated with a corresponding n → σ* orbital interaction. This study examines the role of these n → σ* interactions in stabilizing Si…N tetrel bonding within various dimeric complexes. While conventional n → σ* orbital overlap along the tetrel bonding axis is observed as expected, the findings highlight the presence and significant contribution of additional nonaxial n → σ* orbital interactions in sp-hybridized silicon dimers.

Intranasal Therapeutics for Neurodegenerative Disorders: Overcoming the Blood-Brain Barrier with Smart Formulations and Devices.

Neurodegenerative diseases have always posed a significant therapeutic challenge due to the restrictive nature of the blood-brain barrier (BBB). Intranasal drug delivery has emerged as a noninvasive approach to bypass the BBB, enabling targeted brain drug delivery while improving drug retention and transport. This review explores the physiological basis of the nose-to-brain pathway and various formulation strategies including mucoadhesive systems, permeation enhancers, and magnetophoretic approaches.

Triphenylphosphine-Based Mitochondrial Targeting Nanocarriers: Advancing Cancer Therapy.

Numerous chemotherapeutic drugs are commercially available for cancer treatment; however, their efficacy is often compromised by diminishing therapeutic effectiveness and unpredictable adverse effects. The lack of specific targeting limits their optimal therapeutic potential. Mitochondria are the primary sites of cellular energy production and play a critical role in cell survival and death.

Exploring the remyelinating efficacy of nanoliposomes encapsulating and in a murine model of induced demyelination.

Demyelination leads to neuropathies and clinical deficits. Chemical remyelinating agents have variable efficacy and severe undesirable effects. Withania somnifera and are traditionally known for possessing neuroprotective effects.

Navigating neurodegeneration: challenges, pathophysiology, biomarkers, and the promise of nanocrystals-based nanotherapeutics.

Approximately 90% of drugs struggle with low solubility and non-selectivity in target-specific drug delivery. This creates a significant challenge due to the limited permeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier. Poor solubility, low drug concentration at the target site, and rapid clearance efflux transporters further restrict effective drug delivery in neurodegenerative disorders (NDDs).

Gold Nanoparticles as a Tool to Detect Biomarkers in Osteoarthritis: New Insights.

Extensive research over the years has revealed the remarkable potential of gold nanoparticles (AuNPs) for detecting biomarkers in osteoarthritis (OA). AuNPs are a promising class of nanomaterials offering a wide range of diagnostic and clinical applications. It provides an effective and robust framework for qualitative and quantitative analysis of biomarkers present in the biological fluids of OA patients.

Apolipoprotein-decorated drug loaded liposomes mitigating copper intoxication: an in vitro and in vivo evidence-based study intervening Wilson disease.

Wilson disease (WD), a rare autosomal-recessive disorder caused by impaired copper metabolism, leads to hepatic dysfunction and copper overaccumulation, debilitating neurological symptoms. Current treatments, primarily metal chelating agents and antioxidants, have limitations like sub-optimal efficacy, limited blood-brain barrier transport, and systemic side effects. This study aims to deliver monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a novel next-generation chelator encapsulated in a liposomal nanocarrier coated with apolipoprotein E (ApoE) to enhance brain targeting and copper chelation.

Leveraging Nanoscience and Strategic Delivery for the Expedition of Osteoporosis.

Osteoporosis is a globally affecting bone disease characterized by reduced bone mineral density, in which women are more insidious to the disease. It accounts for 8.9 million fractures annually, and about 50% of repeated hip fractures cause permanent disabilities.

An intelligent federated learning boosted cyberattack detection system for Denial-Of-Wallet attack using advanced heuristic search with multimodal approaches.

In the modern digital era, owing to technological progressions, the diversification and intensity of cyber-attacks have attained an extraordinary level. Unlike network users, intruders use technological developments and implement attacks to cause operational disruptions, data breaches, and financial losses. The Denial-of-Wallet (DoW) attack adapts the standard Denial-of-Service (DoS) attack.

The origin of synthons and supramolecular motifs: beyond atoms and functional groups.

A four-membered R(4) supramolecular motif formed by S...

Synergy of Microfluidics and Nanomaterials: A Revolutionary Approach for Cancer Management.

Cancer affects millions of individuals every year and is the second most common cause of death. Various therapeutic strategies are explored for the management of cancer including radiation therapy and chemotherapy with or without surgical procedures. However, the drawbacks like poor cancer cell targeting and higher toxicity for healthy cells need the advancement of the therapeutic strategy.

siRNA-based Therapeutics in Hormone-driven Cancers: Advancements and benefits over conventional treatments.

Hormone-related cancers, also known as hormone-sensitive or hormone-dependent cancers, rely on hormones such as estrogen, testosterone, and progesterone for growth. These malignancies, including breast, pituitary, thyroid, ovarian, uterine, cervical, and prostate cancers, often exhibit accelerated progression in response to hormonal signaling. Small interfering RNA (siRNA) has emerged as a groundbreaking gene suppression therapy since the FDA approval of its first product in 2018.

Copper-Induced Neurodegenerative Disorders and Therapeutic Potential of Curcumin-Loaded Nanoemulsion.

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side effects, creating a need for safer therapeutic alternatives. To address this, we developed a curcumin-loaded nanoemulsion (CUR-NE) using the spontaneous emulsification technique, aimed at enhancing the bioavailability and therapeutic efficacy of curcumin.

Nano-mediated Management of Metal Toxicity-induced Neurodegeneration: A Critical Review.

Heavy metals, omnipresent in the environment, though imperative in trace quantities for human physiology, become a serious health hazard due to their toxicity. Copper, arsenic, lead, iron, and mercury are some examples of the heavy metals responsible for oxidative stress, which is one of the primary factors behind neurodegenerative diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Neurodegeneration is caused by toxicity due to environmental exposure to these toxic substances or genetic variation.

Pharmacokinetic and Pharmacodynamics of Clofazimine Nano-in-Microparticles: Enhanced Brain Delivery and CNS Tuberculosis Amelioration via Intranasal Administration.

(Mtb) demonstrates a proclivity for infecting extrapulmonary sites, notably the brain. Treating these extrapulmonary tuberculosis (TB) manifestations is challenging due to the difficulty of drug delivery across the blood-brain barrier. Clofazimine (CLF) has exhibited promising activity against Mtb, including multidrug-resistant variants, in vitro and in preclinical animal models.

Modulation of copper-induced neurotoxicity by monoisoamyl 2,3-dimercaptosuccinic acid loaded nanoparticles through inhibition of mitophagy and reduction of oxidative stress in SH-SY5Y cells.

Copper (Cu) dysregulation, often stemming from ATP7B gene mutations, exacerbates neurological disorders like Huntington's, Alzheimer's, and Parkinson's diseases. Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) shows promise in mitigating Cu induced neurotoxicity by chelating intracellular Cu ions, reducing oxidative stress, and restoring antioxidant enzyme function. However, challenges such as poor bioavailability hinder its therapeutic efficacy.

Therapeutic Role of Scutellarein in Neurological Disorders.

Scutellarein, a flavone found in the perennial herb Scutellaria baicalensis, has a wide range of pharmacological actions, such as antioxidant, anti-inflammatory, and neuroprotective. Increasing evidence has emphasized the developing significance of scutellarein in several neurological illnesses, such as Alzheimer's and Parkinson's disease, cerebral ischemia, and neuroblastoma. This review is centered on the molecular processes that underlie the neuroprotective properties of scutellarein in various neurological disorders, as indicated by recent pre-clinical research.

Differential Transcriptional Landscape of Vero Cells During Dengue Virus 2 Infection in the Presence of Sinococuline.

Dengue virus (DENV) is transmitted by genus mosquitoes and is responsible for dengue fever (DF) and other severe diseases, posing a significant challenge to the global health system. Currently, anti-dengue pharmacological treatment options are not available. Earlier, we demonstrated that Sinococuline has potent anti-dengue activity and prevents virus infection.

Investigating the efficacy of gliclazide encapsulated hydrogel in the preclinical mice model for atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin inflammatory ailment commonly observed in young children and adults. Various therapeutic modalities are already explored for mitigation of AD but for prolong application very few modalities are recommended. Considering these challenges, we have successfully developed gliclazide-loaded hydrogels using the physical dispersion method.

Trans-nasal brain delivery of anti-TB drugs by methyl-β-cyclodextrin microparticles show efficient mycobacterial clearance from central nervous system.

Central nervous system tuberculosis (CNS-TB) is the most severe extra-pulmonary manifestation of tuberculosis (TB), facing significant challenges due to the limited penetration of anti-TB drugs (ATDs) across the blood-brain barrier (BBB) and their insufficient concentrations at the site of infection. This study aimed to enhance the efficacy of ATDs by encapsulating them in methyl-β-cyclodextrin (M-β-CD) microparticles (ATD-MP) using spray drying, intended for intranasal delivery to manage CNS-TB. M-β-CD microparticles loaded with isoniazid (INH) and rifampicin (RIF) exhibited spherical shapes with slightly deflated surfaces and particle sizes of 6.

Nondestructive techniques for pharmaceutical drug product characterization.

Pharmaceutical product development involves multiple steps; therefore product quality must be assessed to ensure robustness and acceptability. Raw components, production methods, and ambient conditions yield highly variable end products with low batch-to-batch consistency. Although end testing is performed to ensure product quality, intermediate quality checks are limited.

Zein decorated rifaximin nanosuspension: approach for sustained release and anti-bacterial efficacy enhancement.

The goal of the present work was to formulate zein-decorated rifaximin (RFX) nanosuspension to attain sustained release as well as effectiveness against . The RFX nanosuspension was fabricated by using antisolvent addition method followed by coating using hydroalcoholic zein solution. The optimized RFX-NS and RFX-NS@zein was lyophilized for further spectroscopic evaluations.