Positive impact of DPP-4 or SGLT2 inhibitors on mild cognitive impairment in type 2 diabetes patients on metformin therapy: A metabolomic mechanistic insight.

Mild cognitive impairment is increasingly recognized as a complication of type 2 diabetes (T2D). Although currently no disease-modifying treatments for cognitive disorders exist, interest surged in potential neuroprotective effects of newer anti-diabetic drugs. This study investigates the impact of newer anti-diabetic drug classes, dipeptidyl peptidase-4 (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) - on cognitive decline in T2D patients on metformin therapy.

Treated wastewater reuse and its impact on soil properties and potato and corn growth.

Water scarcity is a growing challenge in semi-arid regions. Many farmers have resorted to treated wastewater (TWW) as an available and low-cost water source. This study investigated the impact of irrigating potato (Solanum Tuberosum) and corn (Zea mays) with tertiary-treated (TW) and secondary-treated (SW) wastewater compared to freshwater, over two years.

Environmental exposure to common pesticide induces synaptic deficit and social memory impairment driven by neurodevelopmental vulnerability of hippocampal parvalbumin interneurons.

Environmental exposure to pesticides at levels deemed safe by regulatory agencies has been linked to increased risk for neurodevelopmental disorders. Yet, the mechanisms linking exposure to these disorders remain unclear. Here, we show that maternal exposure to the pesticide deltamethrin (DM) at the no observed adverse effect level (NOAEL) disrupts long-term potentiation (LTP) in the hippocampus of adult male offspring three months after exposure, a phenotype absent in female offspring.

RNA-dependent RNA polymerase of predominant human norovirus forms liquid-liquid phase condensates as viral replication factories.

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide.

Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most -methyladenosine (mA) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for mA can promote oncogenesis.

Total Syntheses of Scabrolide B, Ineleganolide, and Related Norcembranoids.

Concise total syntheses of several 5/7/6 norcembranoids, including ineleganolide, scabrolide B, sinuscalide C, and fragilolide A have been achieved through a fragment coupling/ring closure approach. The central seven-membered ring was forged through sequential Mukaiyama-Michael/aldol reactions using norcarvone and a decorated bicyclic lactone incorporating a latent electrophile. Subsequent manipulations installed the reactive enedione motif and delivered scabrolide B in 11 steps from a chiral pool-derived enone.

Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives.

Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality.

Fast autofluorescence imaging to evaluate dynamic changes in cell metabolism.

Significance: Cellular metabolic dynamics can occur within milliseconds, yet there are no optimal tools to spatially and temporally capture these events. Autofluorescence imaging can provide metabolic information on the cellular level due to the intrinsic fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD).

Aim: Our goal is to build and evaluate a widefield microscope optimized for rapid autofluorescence imaging of metabolic changes in cells.

Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics.

Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications including tissue engineering, drug delivery, and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires prolonged curing at high temperatures, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production.

Spatiotemporal characterization of the isotopic composition of meteoric waters in Cuba.

The stable isotope composition of meteoric water has been widely used to understand hydrological processes worldwide. We present a unique dataset, with the isotopic composition (δO and δH) of meteoric waters, derived from a nationwide study in Cuba. It includes monthly composite and event-based precipitations, from January 2017 to December 2021 (N = 526 and N = 111 respectively).

Sacrificial Templating for Accelerating Clinical Translation of Engineered Organs.

Transplantable engineered organs could one day be used to treat patients suffering from end-stage organ failure. Yet, producing hierarchical vascular networks that sustain the viability and function of cells within human-scale organs remains a major challenge. Sacrificial templating has emerged as a promising biofabrication method that could overcome this challenge.

Design and synthesis of JNK1-targeted PROTACs and research on the activity.

Kinase dysregulation is greatly associated with cell growth, proliferation, differentiation and apoptosis, which indicates their great potential as therapeutic targets for treatment of numerous progressive disorders, including inflammatory, metabolic and autoimmune disorders, organ fibrosis and cancer. The c‑Jun N‑Terminal Kinase (JNK), as a member of MAPK family, is proved to be a potential target for the treatment of pulmonary fibrosis, which is the most common progressive and fatal fibrotic lung disease. As a new strategy, small-molecule-mediated targeted protein degradation pathway has the advantages of catalytic properties, overcoming drug resistance and expanding target space, which can circumvent the limitations associated with kinase inhibitors.

Microsatellite instability and high tumor mutational burden detected by next generation sequencing are concordant with loss of mismatch repair proteins by immunohistochemistry.

Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI).

Stable isotope tempestology of tropical cyclones across the North Atlantic and Eastern Pacific Ocean basins.

Tropical cyclones (TCs) are one of the major natural hazards to island and coastal communities and ecosystems. However, isotopic compositions of TC-derived precipitation (P) in surface water (SW) and groundwater (GW) reservoirs are still lacking. We tested the three main assumptions of the isotope storm "spike" hypothesis (sudden spikes in isotopic ratios).

Blood biomarker discovery for autism spectrum disorder: A proteomic analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD are currently being investigated.

Uranyl Naphthylsalophen and Pyrasal Complexes: Oxo Ligands Acting as Hydrogen Bond Acceptors in the Solid State.

Uranium is most stable when it is exposed to oxygen or water in its +6 oxidation state as the uranyl (UO) ion. This ion is subsequently particularly stable and very resistant to functionalization due to the inverse trans effect. Uranyl oxo ligands are typically not considered good hydrogen bond acceptors due to their weak Lewis basicity; however, the ligands bound in the equatorial plane greatly affect the strength of the oxo ligands' hydrogen bonding.

Conservation of structure and dynamic behavior in triazine macrocycles with opportunities for subtle control of hinge motion.

Modifying the backbone of 24-atom macrocycles allows tailoring of physical properties (octanol-water partition coefficients, log ) while conserving both conformation and the barrier to dynamic, hinge-like motion. Structure is determined by 1D and 2D NMR spectroscopy. The barrier can be subtly tuned by modifications that appear to preclude fully revolute motion and efficient π-stacking of the two subunits.

Suppressing the Inflammatory Prostaglandin Signaling after Thrombotic Stroke Ameliorates Ischemic Brain Injury and Facilitates Poststroke Recovery.

Acute cerebral ischemia is a leading cause of death and disability, particularly among old adults. The narrow therapeutic window and risk of hemorrhagic transformation largely limit patient eligibility for the current treatment. The neuroinflammatory signaling pathway involving the prostaglandin E2 (PGE) receptor subtype EP2 has now been clarified to contribute to the secondary neurotoxicity following ischemic stroke.

Carbon nanotubes as neuroprotective agents.

Carbon nanotubes, an emerging class of carbon nanomaterials, possess tremendous potential for application in biotechnology and biomedicine particularly in neurological disorders. Carbon nanotubes owing to their fascinating properties have the potential to revolutionize medicine and technology, particularly in the realm of drug delivery, biosensing, bioimaging, and as therapeutic agents to tackle complex neurological disorders such as Alzheimer's and Parkinson's disease. In this review, a summary of the use of carbon nanotubes for neuropathological outcomes such as alleviating oxidative stress and amyloid formation, which are well-studied molecular outcomes associated with Alzheimer's and Parkinson's disease.

Structural mechanism of CBR binding to peripheral and biased inverse agonists.

The cannabinoid receptor 1 (CBR) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CBR antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted their further therapeutic development. The peripherally restricted CBR inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CBR inhibitors while sparing the negative psychiatric effects.

A General Platform for Copper-Catalyzed Atom Transfer Radical Addition with Electron-Deficient Olefins.

We disclose a broad platform for copper-catalyzed atom transfer radical addition (ATRA) of electron-deficient olefins. Catalytic Cu(dtbbpy)(OTf) enables radical addition of electron-deficient alkyl halides to acrylates, acrylamides, and vinyl sulfones in fair to excellent yields. The resultant ATRA products can be used in a variety of telescoped reactions, including substitution with basic amine nucleophiles to afford α-amino esters.

Dually functionalized dendrimer for stimuli-responsive release of active ingredients into the skin.

The skin, our largest organ, protects against environmental dangers but is vulnerable to various conditions like infections, eczema, dermatitis, psoriasis, skin cancer, and age-related collagen and elastin degradation. Its outer layer, the water-impermeable epidermis, presents challenges for passive drug delivery to the lower living layers of the skin. An ideal dermal delivery system should penetrate the epidermis and release treatments over time.

Photochemical oxidation of Cr(III) to Cr(VI) in the presence of Fe(III): Influence of Fe(III) concentration and UV wavelength.

The reduction of Cr(VI) to Cr(III) is key to lowering environmental toxicity and mobility, but the reverse process remains less understood. We investigated Cr(III) oxidation mechanisms across various pH levels and light wavelengths (185, 254, and 358 nm) in the presence of Fe(III). At pH 3.