The critical role of the variable domain in driving proteotoxicity and aggregation in full-length light chains.

Light chain (AL) amyloidosis is the most common systemic amyloid disease characterized by abnormal accumulation of amyloid fibrils derived from immunoglobulin light chains (LCs). Both full-length (FL) LCs and their isolated variable (VL) and constant (CL) domains contribute to amyloid deposits in multiple organs, with the VL domain predominantly forming the fibril core. However, the role and interplay of these domains in amyloid aggregation and toxicity are poorly understood.

Palladium Catalyzed C3-(sp)-H Alkenylation of Pyrroles via a Benzothiazole Directing Group: A Direct Access to Organic Thermally Activated Delayed Fluorescence Materials.

A Pd (II)-catalyzed direct C3-(sp)-H alkenylation of heteroarenes using benzothiazole as a directing group was successfully achieved. A wide range of 2--alkylpyrroles undergo an oxidative coupling with a variety of acrylates to furnish highly regio- and chemoselective E-alkenylation products at the C3 position. An important intermediate complex has been isolated and characterized so as to have an insight into the mechanism.

Chemically Robust Cationic Porous Organic Polymer (POP) for Selective Detection and Removal of ReO as a Surrogate of Radioactive TcO.

The efficient removal of TcO from alkaline nuclear waste is vital for optimizing nuclear waste management and safeguarding the environment. However, current state-of-the-art sorbent materials are constrained by their inability to simultaneously achieve high alkali resistance, rapid adsorption kinetics, large adsorption capacity, and selectivity. In this study, we synthesized a urea-rich cationic porous organic polymer, IPM-403, which demonstrates exceptional chemical stability, ultrafast kinetics (~92 % removal within 30 seconds), high adsorption capacity (664 mg/g), excellent selectivity, along with multiple-cycle recyclability (up to 7 cycles), making it highly promising for the removal of ReO (surrogate of TcO ) from nuclear wastewater.

Visible-Light-Induced Copper-Catalyzed Radical Reactions of Diazo Arylidene Succinimides to Access the Pyromellitic Diimide (PMDI) Core.

The synthesis of pyromellitic diimides (PMDIs) through visible-light-promoted copper-catalyzed reaction of diazo arylidene succinimides has been accomplished without the use of external oxidants. This transformation involves a carbon radical from diazo arylidene succinimides with a copper catalyst or photocatalyst via the proton-coupled electron transfer (PCET) process. This approach successfully challenges a long-standing paradigm in the synthesis of PMDIs.

Star-polymer unimolecular micelle nanoparticles to deliver a payload across the blood-brain barrier.

Nanocarrier-mediated therapeutic delivery to brain tissue is impeded by tightly controlled transportation across the blood-brain barrier (BBB). Herein, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM; a single polymer entity) as an efficient BBB-breaching nanoparticle for brain-specific administration of the fluorescent anticancer drug doxorubicin and mapping of brain tissues by the near-infrared biomarker IR780 in mice. The star-UMM was engineered by precisely programming the polymer topology having hydrophobic and hydrophilic polycaprolactone blocks and in-built with lysosomal enzyme-biodegradation stimuli to deliver the payloads at intracellular compartments.

Chemically robust functionalized covalent organic framework for the highly efficient and selective separation of bromine.

Effective sequestration of bromine holds great promise for the chemical industry's safe expansion, environmental preservation, and public health. However, attaining this goal is still challenging due to the serious drawbacks of existing adsorbents such as limited capacity, low retention efficiency, and sluggish uptake kinetics. Herein, we report a strategy-driven systematic study aimed at significantly enhancing multiple host-guest interactions to obtain functionalized covalent-organic frameworks for the efficient sequestration of bromine.

Biocompatible PVAc--PLLA Acrylate Polymers for DLP 3D Printing with Tunable Mechanical Properties.

The technological advancement of Additive Manufacturing has enabled the fabrication of various customized artifacts and devices, which has prompted a huge demand for multimaterials that can cater to stringent mechanical, chemical, and other functional property requirements. Photocurable formulations that are widely used for Digital Light Processing (DLP)/Stereolithography (SLA) 3D printing applications are now expected to meet these new challenges of hard and soft or stretchable structural requirements in addition to good resolution in multiple scales. Here we present a biocompatible photocurable resin formulation with tunable mechanical properties that can produce hard or stretchable elastomeric 3D printed materials in a graded manner.

The Reactivity of Acceptor-Acceptor Diazo Pyrazolones with Allyl Thioethers under Visible Light: Access to Homoallyl Sulfides, Spiropyrazolones - Pesticide Analogues and Photoflow Synthesis.

The novel reactivity of a less selective and more reactive acceptor-acceptor kind of diazo pyrazolone (DIPOL) has been explored under visible light for the first time. We have successfully demonstrated the reaction of DIPOL and different allyl thioethers under blue light to construct a wide variety of products including a pesticidal analogue exclusively in excellent chemoselectivity in good to excellent yields. Moreover, possible side products emanating from ketene were not observed.

Melt Polycondensation Strategy to Access Unexplored l-Amino Acid and Sugar Copolymers.

Biodegradable polymers from bioresources are highly in demand for the development of sustainable polymer platforms for commodity plastics and in the biomedical field. Here, an elegant one-pot synthetic strategy is developed, for the first time, to access unexplored hybrid polymers from two naturally abundant resources: carbohydrates (sugars) and l-amino acids. A bottleneck in the synthetic strategy is overcome by tailor-making d-mannitol-based six- and five-membered bicyclic acetalized diols, and their structures are confirmed by single-crystal X-ray diffraction and 2D NMR spectroscopy.

A nanotrap infused ultrathin hybrid composite material for rapid and highly selective entrapment of TcO.

Tc is one of the potentially toxic radioactive substances owing to its long half-life and a high degree of environmental mobility. Hence, the sequestration of Tc from radioactive waste has become enormously important and a contemporary research priority. However, selective extraction of this species in its stable oxoanionic form (TcO ) is very challenging on account of bottlenecks such as low charge density, less hydrophilic nature, Herein, an ultrathin hybrid composite material has been strategically designed and fabricated by covalent anchoring of a chemically stable amino functionalized nanosized cationic metal-organic polyhedron with a positively charged robust ionic covalent organic framework.

Thieno[3,2-b]thiophene Incorporated Redox Active 22π and 34π Core-Modified Expanded Isophlorinoids.

Incorporation of a thieno[3,2-b]thiophene into an isophlorinoid-like framework alters the aromaticity by extending the macrocyclic π-circuit. Their opto-electronic and aromatic properties significantly differ from other 22π and 34π porphyrinoids. Among the three different 34π hexaphyrins, furan based hexaphyrin adopts a non-aromatic 'figure-of-eight' conformation.

Rational Monomer Design for the Synthesis of Conjugated Polymers by Direct Heteroarylation Polymerization.

This study focuses on the design concepts that contribute to the C-H activation in bithiophene-flanked monomers incorporating naphthalene diimide (NDI), perylene diimide (PDI), and fluorene (FLU) and their polymerization by direct heteroarylation. Density functional theory (DFT) calculations reveal distinct energy requirements for C-H bond abstraction, which is dictated by the electron-withdrawing strength of the central aromatic core flanked by bithiophene. These provide insights into the reactivity of each monomer for C-H bond activation.

Structural Engineering of l-Aspartic Amphiphilic Polyesters for Enzyme-Responsive Drug Delivery and Bioimaging in Cancer Cells.

Design and development of amphiphilic polyesters based on bioresources are very important to cater to the ever-growing need for biodegradable polymers in biomedical applications. Here, we report structural engineering of enzyme-responsive amphiphilic polyesters based on l-amino acid bioresources and study their drug delivery aspects in the cancer cell line. For this purpose, an l-aspartic acid-based polyester platform is chosen, and two noncovalent forces such as hydrogen bonding and side-chain hydrophobic interactions are introduced to study their effect on the aqueous self-assembly of nanoparticles.

Visible Light-Induced Organophotoredox-Catalyzed β-Hydroxytrifluoromethylation of Unactivated Alkenes.

Herein, we report a mild transition metal-free organophotoredox-catalyzed approach for β-hydroxytrifluoromethylation of unactivated alkenes using CFSONa and acridinium salt. The protocol is compatible with various mono-, di-, and trisubstituted aliphatic unactivated alkenes containing numerous functional groups and natural product derivatives. Further, the postsynthetic modifications of the synthesized trifluoromethylated products have been demonstrated through cross-coupling and functional group interconversion reactions.

Photosensitizer-Free Photoinduced Ground-State Triplet Carbene-Assisted Persistent Aryloxy Radical Generation via Hydrogen Atom Transfer.

The traditional intermolecular O-H insertion strategy is typically associated with the reactivity exhibited by the singlet spin state, or it can alter the spin state from triplet to singlet by hydrogen bonding. Herein, we report diazoarylidene succinimide that generates a persistent ground-state triplet carbene under visible light (Blue LED, 456 nm) without a photosensitizer. This triplet carbene undergoes an intramolecular O-H insertion via hydrogen atom transfer, forming a persistent aryloxy radical without altering its spin state and leading to biologically relevant 2-chromenes.

Switchable molecular electrocatalysis.

We demonstrate a switchable electrocatalysis mechanism modulated by hydrogen bonding interactions in ligand geometries. By manipulating these geometries, specific electrochemical processes at a single catalytic site can be selectively and precisely activated or deactivated. The α geometry enhances dioxygen electroreduction (ORR) while inhibiting protium redox processes, with the opposite effect seen in the β geometry.

Individual-specific associations between warble song notes and body movements in budgerigar courtship displays.

Complex behavioral sequences such as courtship displays are often multimodal, and coordination between modalities is critically important. In learned and variable behavioural sequences such as songs, individual variability may also extend to multimodal coordination and the associations between modalities. However, individual variability in complex multimodal sequences and in coordination between distinct behaviours remains underexplored.

Silylene-Copper-Amide Emitters: From Thermally Activated Delayed Fluorescence to Dual Emission.

Herein, we report the inaugural instance of N-heterocyclic silylene (NHSi)-coordinated copper amide emitters (2-5). These complexes exhibit thermally activated delayed fluorescence (TADF) and singlet-triplet dual emission in anaerobic conditions. The NHSi-Cu-diphenylamide (2) complex demonstrates TADF with a very small ΔE gap (0.

A critical review on the organo-metal(loid)s pollution in the environment: Distribution, remediation and risk assessment.

Toxic metal(loid)s, e.g., mercury, arsenic, lead, and cadmium are known for several environmental disturbances creating toxicity to humans if accumulated in high quantities.

Interrogating the Molecular Clutch in Neuronal Growth Cones: Measuring Traction Forces, F-actin Retrograde Flow, and Point Contact Demographics.

Growth cone-dependent outgrowth of neuronal processes is essential for the development, plasticity, and regenerative capacity of the nervous system. This process involves the attachment of the growth cone to the substrate and the cyclical engagement/disengagement of the molecular clutch at the sites of adhesive contact. In this chapter, we describe protocols for traction force microscopy, measurement of F-actin retrograde flow velocities, and the assessment of adhesive point contacts by immunofluorescence.

Supramolecular polyplexes from Janus peptide nucleic acids (bm-PNA-G5): self-assembled bm-PNA G-quadruplex and its tetraduplex with DNA.

Nucleic acids (DNA and RNA) can form diverse secondary structures ranging from hairpins to duplex, triplex, G4-tetraplex and C4-i-motifs. Many of the DNA analogues designed as antisense oligonucleotides (ASO) are also adept at embracing such folded structures, although to different extents with altered stabilities. One such analogue, peptide nucleic acid (PNA), which is uncharged and achiral, forms hybrids with complementary DNA/RNA with greater stability and specificity than DNA:DNA/RNA hybrids.

Selection for greater dispersal in early life increases rate of age-dependent decline in locomotor activity and shortens lifespan.

Locomotor activity is one of the major traits that is affected by age. Greater locomotor activity is also known to evolve in the course of dispersal evolution. However, the impact of dispersal evolution on the functional senescence of locomotor activity is largely unknown.

A Facile LC-MS Method for Profiling Cholesterol and Cholesteryl Esters in Mammalian Cells and Tissues.

Cholesterol is central to mammalian lipid metabolism and serves many critical functions in the regulation of diverse physiological processes. Dysregulation in cholesterol metabolism is causally linked to numerous human diseases, and therefore, in vivo, the concentrations and flux of cholesterol and cholesteryl esters (fatty acid esters of cholesterol) are tightly regulated. While mass spectrometry has been an analytical method of choice for detecting cholesterol and cholesteryl esters in biological samples, the hydrophobicity, chemically inert nature, and poor ionization of these neutral lipids have often proved a challenge in developing lipidomics compatible liquid chromatography-mass spectrometry (LC-MS) methods to study them.

Effect of developmental and adult diet composition on reproductive aging in Drosophila melanogaster.

Diet significantly affects reproductive outcomes across species, yet the precise effects of macronutrient compositions beyond caloric intake on reproductive aging are understudied. Existing literature presents conflicting views on the fertility impacts of nutrient-rich versus nutrient-poor developmental diets, underscoring a notable research gap. This study addresses these gaps by examining effects of isocaloric diets with varied protein-to-carbohydrate ratios during both developmental and adult stages on reproductive aging of a large, outbred Drosophila melanogaster population (n = ∼2100).