Wafer-scale nanofabrication of sub-5 nm gaps in plasmonic metasurfaces.

In the rapidly evolving field of plasmonic metasurfaces, achieving homogeneous, reliable, and reproducible fabrication of sub-5 nm dielectric nanogaps is a significant challenge. This article presents an advanced fabrication technology that addresses this issue, capable of realizing uniform and reliable vertical nanogap metasurfaces on a whole wafer of 100 mm diameter. By leveraging fast patterning techniques, such as variable-shaped and character projection electron beam lithography (EBL), along with atomic layer deposition (ALD) for defining a few nanometer gaps with sub-nanometer precision, we have developed a flexible nanofabrication technology to achieve gaps as narrow as 2 nm in plasmonic nanoantennas.

Synthesis and Structure-Activity Relationships for Glutamate Transporter Allosteric Modulators.

Excitatory amino acid transporters (EAATs) are essential CNS proteins that regulate glutamate levels. Excess glutamate release and alteration in EAAT expression are associated with several CNS disorders. Previously, we identified positive allosteric modulators (PAM) of EAAT2, the main CNS transporter, and have demonstrated their neuroprotective properties .

A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins.

In the field of drug discovery, understanding how small molecule drugs interact with cellular components is crucial. Our study introduces a novel methodology to uncover primary drug targets using andem ffinity urification for identification of rug-inding roteins (TAP-DBP). Central to our approach is the generation of a FLAG-hemagglutinin (HA)-tagged chimeric protein featuring the FKBP12(F36V) adaptor protein and the TurboID enzyme.

Injectable On-Demand Pulsatile Drug Delivery Hydrogels Using Alternating Magnetic Field-Triggered Polymer Glass Transitions.

Remote-controlled pulsatile or staged release has significant potential in a wide range of therapeutic treatments. However, most current approaches are hindered by the low resolution between the on- and off-states of drug release and the need for surgical implantation of larger controlled-release devices. Herein, we describe a method that addresses these limitations by combining injectable hydrogels, superparamagnetic iron oxide nanoparticles (SPIONs) that heat when exposed to an alternating magnetic field (AMF), and polymeric nanoparticles with a glass transition temperature () just above physiological temperature.

Enhancement of third harmonic generation induced by surface lattice resonances in plasmonic metasurfaces.

We investigate experimentally third harmonic generation (THG) from plasmonic metasurfaces consisting of two-dimensional rectangular lattices of centrosymmetric gold nanobars. By varying the incidence angle and the lattice period, we show how surface lattice resonances (SLRs) at the involved wavelengths are the major contributors in determining the magnitude of the nonlinear effects. A further boost on THG is observed when we excite together more than one SLR, either at the same or at different frequency.

Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer.

Unlabelled: Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC and designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding and VHL recruitment.

Second harmonic generation under doubly resonant lattice plasmon excitation.

Second harmonic generation is enhanced at the surface lattice resonance in plasmonic nanoparticle arrays. We carried out a parametric investigation on two-dimensional lattices composed of gold nanobars where the centrosymmetry is broken at oblique incidence. We study the influence of the periodicity, the incidence angle and the direction of the linear input polarization on the second harmonic generation.

SmI -mediated C-alkylation of Ketones with Alcohols under Microwave Conditions: A Novel Route to Alkylated Ketones.

A novel protocol is developed towards the preparation of alkylated ketones from alcohols in presence of catalytic amount of SmI and base with the elimination of water as a single by-product under microwave irradiation conditions. Furthermore, applicability of this methodology to the synthesis of Donepezil and late-stage functionalization in Pregnenolone is also reported. Successful application of this methodology in Friedländer quinolone synthesis using 2-aminobenzyl alcohol and various acetophenones expand the synthetic utility of this protocol.

Copper mediated one-pot synthesis of quinazolinones and exploration of piperazine linked quinazoline derivatives as anti-mycobacterial agents.

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction amine generation using ammonia as the amine source and with the formation of four new C-N bonds in good to excellent yields. With the optimised method, we synthesized a library of piperazine linked quinazoline derivatives and the synthesized compounds were evaluated for their inhibitory activity against . The compounds 8b, 8e, 8f, 8m, 8n and 8v showed potent anti-mycobacterial activity with MIC values of 2-16 μg mL.

Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors.

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer.

Recent developments in the general atomic and molecular electronic structure system.

A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory.

Facile synthesis of 1,2,3-triazole-fused indolo- and pyrrolo[1,4]diazepines, DNA-binding and evaluation of their anticancer activity.

A facile synthetic strategy has been developed for the generation of structurally diverse N-fused heterocycles. The formation of fused 1,2,3-triazole indolo and pyrrolodiazepines proceeds through an initial Knoevenagel condensation followed by intramolecular azide-alkyne cycloaddition reaction at room temperature without recourse to the traditional Cu(I)-catalyzed azide-alkyne cycloadditions. The synthesized compounds were evaluated for their in vitro anti-cancer activity against the NCI 60 cell line panel.

Capsaicin has potent anti-oxidative effects through a mechanism which is non-receptor mediated.

Capsaicin (8-methyl-N-vanillyl--6-nonenamide) is the active ingredient of chilli peppers and is responsible for the characteristic pungency. The ubiquitous human consumption of chilli peppers indicates their influence on human health. The effect of capsaicin through sensory neurons via TRPV1 activation has been well studied, but its non-neuronal effects are still not extensively explored.

Catalyst-free facile synthesis of polycyclic indole/pyrrole substituted-1,2,3-triazoles.

A general and catalyst-free access to the fused polycyclic N-heterocycles via an intramolecular azide-alkene cascade reaction under mild reaction conditions has been developed. The reaction is applicable to both indole and pyrrole substrates, and a variety of substituents are tolerated. The entire sequence can be carried out in a one-pot operation.

Natural product derived promising anti-MRSA drug leads: A review.

Multi-drug resistant Staphylococcus aureus infections have created a critical need for the development of new classes of antibacterials. Discovery of new naturally derived antibacterial agents with new mechanism of action remains a high priority globally. Several of the available antibacterial agents like β-lactams, polyketides, phenylpropanoids, aminoglycosides, macrolides, glycopeptides, streptogramins and lipopeptides are natural products or their semisynthetic variations.

Synthesis and evaluation of new quinazolin-4(3H)-one derivatives as potent antibacterial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis.

Staphylococcus aureus and Mycobacterium tuberculosis are major causative agents responsible for serious nosocomial and community-acquired infections impacting healthcare systems globally. Over several decades, these pathogens have developed resistance to multiple antibiotics significantly affecting morbidity and mortality. Thus, these recalcitrant pathogens are amongst the most formidable microbial pathogens for which international healthcare agencies have mandated active identification and development of new antibacterial agents for chemotherapeutic intervention.

A Microwave-Assisted SmI-Catalyzed Direct N-Alkylation of Anilines with Alcohols.

A new protocol for the alkylation of aromatic amines has been described using alcohols in the presence of SmI as a catalyst with the generation of water as the sole byproduct. The reaction proceeds under MW conditions and selectively generates monoalkylated amines. This protocol features a broad substrate scope and good functional-group tolerance with moderate to high yields.

Synthesis and evaluation of new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives as potent antibacterial agents effective against multidrug resistant Staphylococcus aureus.

Treatment of nosocomial and community acquired Staphylococcus aureus infections has become more challenging due to the egression of multi-drug resistance. This has spurred the need for rapid development of new therapeutic agents which can effectively negate the resistance mechanisms. In our current work, several new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives were synthesized and examined for their antimicrobial activity against ESKAP pathogen panel and pathogenic mycobacteria.

Synthesis of 1,2,3-triazole linked 4(3H)-Quinazolinones as potent antibacterial agents against multidrug-resistant Staphylococcus aureus.

Methicillin and vancomycin resistant Staphylococcus aureus infections are an emerging global health concern leading to increasing morbidity and mortality. Continuous increase in drug resistance has underlined the need for discovery and development of new antibacterial agents acting via novel mechanisms to overcome this pressing issue. In this context, a number of 1,2,3-triazole linked 4(3H)-quinazolinone derivatives were designed and synthesized as potent antibacterial agents.

Synthesis of new 3-phenylquinazolin-4(3H)-one derivatives as potent antibacterial agents effective against methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA).

Occurrence of infections due to the drug resistant Staphylococcus aureus is on rise necessitating the need for rapid development of new antibacterial agents. In our present work, a series of new 3-phenylquinazolin-4(3H)-one derivatives were designed, synthesized and evaluated for their antibacterial activity against ESKAP (E. coli, S.

Validated stability indicating assay method of olaparib: LC-ESI-Q-TOF-MS/MS and NMR studies for characterization of its new hydrolytic and oxidative forced degradation products.

Olaparib (OLA) is a poly ADP ribose polymerase (PARP) enzyme inhibitor used to treat prostate, ovarian and breast cancer. The drug substance OLA was subjected to forced degradation as per ICH prescribed guidelines. It was degraded in hydrolytic (acidic and basic) and oxidative stress conditions and yielded four degradation products (DPs) while it remained stable in neutral hydrolytic, dry heat and photolytic stress conditions.

Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents.

A series of imidazo[2,1-b]thiazole-benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines i.e.; HeLa (cervical), A549 (lung), MCF-7 (breast) and DU-145 (prostate) along with normal HEK-293 cell line.

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks.

Cyanobacteria, Lyngbya aestuarii and Aphanothece bullosa as antifungal and antileishmanial drug resources.

Objective: To investigate two cyanobacteria isolated from different origins i.e. Lyngbya aestuarii (L.

Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production.

Growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. Notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. In this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation.