Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome.

Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy in animal models. However, the mechanisms by which Spns1 transports lysophospholipid and proton sensing remain unclear.

Electrostatic Force-Enabled Microneedle Patches that Exploit Photoredox Catalysis for Transdermal Phototherapy.

Microneedle patches for topical administration of photodynamic therapy (PDT) sensitizers are attractive owing to their safety, selectivity, and noninvasiveness. However, low-efficiency photosensitizer delivery coupled with the limitations of the hypoxic tumor microenvironment remains challenging. To overcome these issues, we developed an effective microneedle patch based on intermolecular electrostatic interactions within a photosensitizer matrix containing a zinc-containing porphyrin analogue, .

Dynamic and electrophoretic light scattering measurements on microtubules at low concentrations.

The accurate characterization of microtubules is essential for understanding their roles in various biological activities in eukaryotic cellular processes. In vitro, experimental data on these systems often need more details and information on sample preparation protocols and experimental techniques. This deficiency leads to unreproducible or contradictory outcomes.

Synthesis And Photovoltaic Performance of Carbazole (Donor) Based Photosensitizers in Dye-Sensitized Solar Cells (DSSC): A Review.

Carbazoles are nitrogen-containing aromatic heterocycles, having widespread applications in the field of photovoltaics. Carbazole-based photosensitizers have tunable features for absorption on semi-conductor (tellurium dioxide or zinc oxide) layers to create sufficient push-pull force in the conversion of sunlight into electrical energy, thus presenting as promising heterocyclic donor candidates to be used in dye-sensitized solar cells. For the synthesis of these dyes, various structural designs are available, namely, D-A, D-π-A, D-D-π-A, D-A-π-A, A-π-D-π-A-π-A, and D2-π-A that all involve incorporating carbazole as a donor (D), along with spacer (π-extender) moieties, such as thiophene, phenol, ethynylene, nitromethane, azine, thiadiazole, or acetonitrile.

Understanding the synergistic interaction between a 1,3,4-thiadiazole derivative and amphotericin B using spectroscopic and theoretical studies.

We present a comprehensive spectroscopic study supported by theoretical quantum chemical calculations conducted on a molecular system (4-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C1) and the antibiotic Amphotericin B (AmB)) that exhibits highly synergistic properties. We previously reported the strong synergism of this molecular system and now wish to present related stationary measurements of UV-Vis absorption, fluorescence, and fluorescence anisotropy in a polar, aprotic solvent (DMSO and a PBS buffer), followed by time-resolved fluorescence intensity and anisotropy decay studies using different ratios of the selected 1,3,4-thiadiazole derivative to Amphotericin B. Absorption spectra measured for the system revealed discrepancies in terms of the shapes of absorption bands, particularly in PBS.

Strontium isoscape of sub-Saharan Africa allows tracing origins of victims of the transatlantic slave trade.

Strontium isotope (Sr/Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving Sr/Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the Sr/Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression.

A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth.

Clade 2.3.4.

Amorphous Carbon Monolayer: A van der Waals Interface for High-Performance Metal Oxide Semiconductor Devices.

Ultrasmall-scale semiconductor devices (≤5 nm) are advancing technologies, such as artificial intelligence and the Internet of Things. However, the further scaling of these devices poses critical challenges, such as interface properties and oxide quality, particularly at the high-/semiconductor interface in metal-oxide-semiconductor (MOS) devices. Existing interlayer (IL) methods, typically exceeding 1 nm thickness, are unsuitable for ultrasmall-scale devices.

Dual-fluorescent starch biopolymer films containing 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine powder as a functional nanofiller.

Physical and photophysical properties of starch-based biopolymer films containing 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine (NTA) powder as a nanofiller were examined using atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR), stationary UV-Vis and fluorescence spectroscopy as well as resonance light scattering (RLS) and time-resolved measurements, and where possible, analyzed with reference to pristine NTA solutions. AFM studies revealed that the addition of NTA into the starch biopolymer did not significantly affect surface roughness, with all examined films displaying similar Sq values ranging from 70.7 nm to 79.

Bayesian semiparametric inference in longitudinal metabolomics data.

The article is motivated by an application to the EarlyBird cohort study aiming to explore how anthropometrics and clinical and metabolic processes are associated with obesity and glucose control during childhood. There is interest in inferring the relationship between dynamically changing and high-dimensional metabolites and a longitudinal response. Important aspects of the analysis include the selection of the important set of metabolites and the accommodation of missing data in both response and covariate values.

Amperometric determination of NADH and dehydrogenase enzymes at a redox-active nanocomposite.

Aminated carbon nanotubes, CNT, were covalently modified with glutardialdehyde (GDI) and the redox dye Azure to form a new electrode material CNT-GDI-Azure (CGA). The nanocomposite of CGA and polysaccharide chitosan was used for the anodic determination of NADH. Compared to conventional carbon and metal electrodes, the CGA electrode drastically lowered the overpotential for NADH oxidation (by > 0.

Improved Control of Triple-Negative Breast Cancer Tumor and Metastasis with a pH-Sensitive Hyaluronic Acid Nanocarrier for Doxorubicin Delivery.

Polymer based nanoformulations offer substantial prospects for efficacious chemotherapy delivery. Here, we developed a pH-responsive polymeric nanoparticle based on acidosis-triggered breakdown of boronic ester linkers. A biocompatible hyaluronic acid (HA) matrix served as a substrate for carrying a doxorubicin (DOX) prodrug which also possesses natural affinity for CD44 cells.

SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.

Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.

PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons.

Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages.

In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.

Biochar reduces containerized pepper blight caused by Phytophthora Capsici.

Phytophthora blight caused by Phytophthora capsici is a serious disease affecting a wide range of plants. Biochar as a soil amendment could partially replace peat moss and has the potential to suppress plant diseases, but its effects on controlling phytophthora blight of container-grown peppers have less been explored, especially in combination of biological control using Trichoderma. In vitro (petri dish) and in vivo (greenhouse) studies were conducted to test sugarcane bagasse biochar (SBB) and mixed hardwood biochar (HB) controlling effects on pepper phytophthora blight disease with and without Trichoderma.

Assembly of Pyrenes through a Quadruple Photochemical Cascade: Blocking Groups Allow Diversion from the Double Mallory Path to Photocyclization at the Bay Region.

We present a six-step cascade that converts 1,3-distyrylbenzenes (-stilbenes) into nonsymmetric pyrenes in 40-60% yields. This sequence merges photochemical steps, ,-alkene isomerization, a 6π photochemical electrocyclization (Mallory photocyclization); the new bay region cyclization, with two radical iodine-mediated aromatization steps; and an optional aryl migration. This work illustrates how the inherent challenges of engineering excited state reactivity can be addressed by logical design.

Passive accumulation of alkaloids in inconspicuously colored frogs refines the evolutionary paradigm of acquired chemical defenses.

Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended.

The Effect of Purified Opharin Isolated from the Venom of King Cobra () in Modulating Macrophage Inflammatory Responses and Vascular Integrity.

King cobra () venom comprises a diverse array of proteins and peptides. However, the roles and properties of these individual components are still not fully understood. Among these, Cysteine-rich secretory proteins (CRiSPs) are recognized but not fully characterized.

Pleozymes: Pleiotropic Oxidized Carbon Nanozymes Enhance Cellular Metabolic Flexibility.

Our group has synthesized a pleiotropic synthetic nanozyme redox mediator we term a "pleozyme" that displays multiple enzymatic characteristics, including acting as a superoxide dismutase mimetic, oxidizing NADH to NAD, and oxidizing HS to polysulfides and thiosulfate. Benefits have been seen in acute and chronic neurological disease models. The molecule is sourced from coconut-derived activated charcoal that has undergone harsh oxidization with fuming nitric acid, which alters the structure and chemical characteristics, yielding 3-8 nm discs with broad redox potential.

Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia.

Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures of graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as "pleozymes". A broad redox potential spans many crucial redox reactions including the oxidation of hydrogen sulfide (HS) to polysulfides and thiosulfate, dismutation of the superoxide radical (O*), and oxidation of NADH to NAD.

Antibody-mediated clearance of an ER-resident aggregate that causes glaucoma.

Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several antibodies that inhibit aggregation are approved or in clinical trials to treat Alzheimer's disease. Here, we developed antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma and cause early onset vision loss for several million individuals worldwide. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER).

An in silico framework to visualize how cancer-associated mutations influence structural plasticity of the chemokine receptor CCR3.

G protein Coupled Receptors (GPCRs) are the largest family of cell surface receptors in humans. Somatic mutations in GPCRs are implicated in cancer progression and metastasis, but mechanisms are poorly understood. Emerging evidence implicates perturbation of intra-receptor activation pathway motifs whereby extracellular signals are transmitted intracellularly.

Influence of Ligand Complexity on the Spectroscopic Properties of Type 1 Copper Sites: A Theoretical Study.

Multi-copper oxidases (MCOs) are enzymes of significant interest in biotechnology due to their efficient catalysis of oxygen reduction to water, making them valuable in sustainable energy production and bio-electrochemical applications. This study employs time-dependent density functional theory (TDDFT) to investigate the electronic structure and spectroscopic properties of the Type 1 (T1) copper site in Azurin, which serves as a model for similar sites in MCOs. Four model complexes of varying complexity were derived from the T1 site, including 3 three-coordinate models and 1 four-coordinate model with axial methionine ligation, to explore the impact of molecular branches and axial coordination.