Relationship between structural properties and biological activity of (-)-menthol and some menthyl esters.

Menthol is a naturally occurring cyclic terpene alcohol and is the major component of peppermint and corn mint essential oils extracted from Mentha piperita L. and Mentha arvensis L..

New cinnamic acid sugar esters as potential UVB filters: Synthesis, cytotoxicity, and physicochemical properties.

Cinnamic Acid Sugar Ester Derivatives (CASEDs) are a class of natural compounds that exhibit several interesting biological activities. However, to date, no examples of their use in sunscreen formulations have been reported. Here, we describe the synthesis of a series of novel cinnamic acid esters of glucose (4a-g), ribose (4h) and lactose (4i) starting from the respective acetals 3.

Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.

The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.

Controlling spiral wave dynamics of the BZ system in a modified Oregonator model: From suppression to turbulence.

Spirals are a special class of excitable waves that have its significance in the understanding of cardiac arrests and neuronal transduction. In a theoretical model of the chemical Belousov-Zhabotinsky reaction system, we explore the dynamics of the spatiotemporal patterns that emerge out of competing reaction and diffusion phenomena. By modifying the existing mathematical models of the reaction kinetics, we have been able to explore the explicit effect of hydrogen ion concentration in the system, so as to achieve various regimes of wave activity, from stable spirals to oscillation death.

Polylactic Acid Micro/Nanoplastic Exposure Induces Male Reproductive Toxicity by Disrupting Spermatogenesis and Mitochondrial Dysfunction in Mice.

Although considered an "eco-friendly" biodegradable plastic, polylactic acid (PLA) microplastic (PLA-MP) poses a growing concern for human health, yet its effects on male reproductive function remain underexplored. This study investigated the reproductive toxicity of PLA in male mice and its potential mechanisms. To this end, our in vivo and in vitro experiments demonstrated that after degradation in the digestive system, a significant number of PLA-MP-derived nanoparticles could penetrate the blood-testis barrier (BTB) and localize within the spermatogenic microenvironment.

Understanding the Topology Freezing Temperature of Vitrimer-Like Materials through Complementary Structural and Rheological Analyses for Phase-Separated Network.

Vitrimers are sustainable cross-linked polymers characterized by an associative bond exchange mechanism within their network. A well-known feature of vitrimers is the Arrhenius dependence of the viscosity or relaxation time. Another important aspect is the existence of a topology-freezing temperature (), which represents a transition between the viscoelastic solid state and the malleable viscoelastic liquid state.

Synthesis and Characterization of Homo- and Heteroleptic Neptunium(IV) Heteroarylalkenolate Complexes.

Heteroleptic An (An = U, Np) chlorido-ketoenaminate complexes of the type [AnCl(TFB-BuA)(THF)] ( type: , ; TFB-BuA = 4-(-butylamino)-1,1,1-trifluorobut-3-en-2-one) and the homoleptic Np heteroarylalkenolate complexes [Np(PyTFP)] (, PyTFP = 1-(pyridin-2-yl)-3,3,3-trifluoroprop-1-en-2-ol) and [Np(DMOTFP)] (, DMOTFP = 1-(4,5-dimethyloxazol-2-yl)-3,3,3-trifluoroprop-1-en-2-ol) were synthesized and characterized (SC-XRD, NMR, Vis-NIR, MS). While their solid-state structures compare well to those of their uranium analogues, the behavior in solution showed significant differences. The binding motif of the DMOTFP ligand in complex can change to form two different complex isomers, as seen by paramagnetic chemical shifts in NMR experiments.

Relativistic CASPT2/RASPT2 Program along with DIRAC Software.

Exploring electronic states in actinide compounds is a critical aspect of nuclear science. However, considering relativistic effects and electron correlation in theoretical calculations poses a complex challenge. To tackle this, we developed the CASPT2/RASPT2 program along with the DIRAC program, enabling calculations of electron correlation methods using multiconfigurational perturbation theory with various relativistic Hamiltonians.

Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.

Purpose: MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined.

Understanding the Dual Role of Macrophages in Tumor Growth and Therapy: A Mechanistic Review.

Macrophages are heterogeneous cells that are the mediators of tissue homeostasis. These immune cells originated from monocytes and are classified into two basic categories, M1 and M2 macrophages. M1 macrophages exhibit anti-tumorous inflammatory reactions due to the behavior of phagocytosis.

New Layered Boride NiPtB ( = 0.5) with a Ternary Derivative Structure of MoB.

A novel ternary boride, NiPtB ( = 0.5), was obtained by argon-arc melting of the elements followed by annealing at 750 °C. It exhibits a new structure type with the space group ( = 2.

Rational Design of Nanozymes for Engineered Cascade Catalytic Cancer Therapy.

Nanozymes have shown significant potential in cancer catalytic therapy by strategically catalyzing tumor-associated substances and metabolites into toxic reactive oxygen species (ROS) , thereby inducing oxidative stress and promoting cancer cell death. However, within the complex tumor microenvironment (TME), the rational design of nanozymes and factors like activity, reaction substrates, and the TME itself significantly influence the efficiency of ROS generation. To address these limitations, recent research has focused on exploring the factors that affect activity and developing nanozyme-based cascade catalytic systems, which can trigger two or more cascade catalytic processes within tumors, thereby producing more therapeutic substances and achieving efficient and stable cancer therapy with minimal side effects.

Functionalized Terthiophene as an Ambipolar Redox System: Structure, Spectroscopy, and Switchable Proton-Coupled Electron Transfer.

Organic redox systems that can undergo oxidative and reductive (ambipolar) electron transfer are elusive yet attractive for applications across synthetic chemistry and energy science. Specifically, the use of ambipolar redox systems in proton-coupled electron transfer (PCET) reactions is largely unexplored but could enable "switchable" reactivity wherein the uptake and release of hydrogen atoms are controlled using a redox stimulus. Here, we describe the synthesis and characterization of an ambipolar functionalized terthiophene (TTH) bearing methyl thioether and phosphine oxide groups that exhibits switchable PCET reactivity.

A Fast-Pass, Desorption Electrospray Ionization Mass Spectrometry Strategy for Untargeted Metabolic Phenotyping.

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) provides direct analytical readouts of small molecules that can be used to characterize the metabolic phenotypes of genetically engineered bacteria. In an effort to accelerate the time frame associated with the screening of mutant libraries, we have developed a high-throughput DESI-MSI analytical workflow implementing a single raster line-scan strategy that facilitates the collection of location-resolved molecular information from engineered strains on a subminute time scale. Evaluation of this "Fast-Pass" DESI-MSI phenotyping workflow on analytical standards demonstrated the capability of acquiring full metabolic profiling information with a throughput of ∼40 s per sample.

Circular Polymer Designed by Regulating Entropy: Spiro-Valerolactone-Based Polyesters with High Gas Barriers and Adhesion Strength.

Enthalpy is often the focal point when designing monomers for polymer circularity, but much less is explored on how entropy can be exploited to create polymers with synergistic circularity and properties. Here, we design a series of spiro-lactones (SLs) with closed-chain cycloalk(en)yl substituents at the α,α-position of δ-valerolactone (δVL), which, when combined with the parent δVL and -α,α-dialkyl-substituted δVL with open-chain alkyl groups, provide a desired platform for exploring the circular polymer design by focusing on the entropy change of polymerization. These SLs exhibit finely balanced (de)polymerizability that is regulated chiefly by entropy differentiation, allowing both the facile synthesis of polyester PSLs ( up to 1000 kg mol) in a living fashion and selective depolymerization of the PSLs to completely recover monomers under mild conditions (using a recyclable catalyst at 100 °C).

Accumulation of Water-Soluble Polysaccharides during Lychee Pulp Fermentation with Involves Endoglucanase Expression.

In the current work, lychee pulp was subjected to ATCC 14917 fermentation, leading to a substantial increase (2.32-2.67-fold) in water-soluble polysaccharides (WSP).

Specificity and tunability of efflux pumps: A new role for the proton gradient?

Efflux pumps that transport antibacterial drugs out of bacterial cells have broad specificity, commonly leading to broad spectrum resistance and limiting treatment strategies for infections. It remains unclear how efflux pumps can maintain this broad spectrum specificity to diverse drug molecules while limiting the efflux of other cytoplasmic content. We have investigated the origins of this broad specificity using theoretical models informed by the experimentally determined structural and kinetic properties of efflux pumps.

Suppressing Tymovirus replication in plants using a variant of ubiquitin.

RNA viruses have evolved numerous strategies to overcome host resistance and immunity, including the use of multifunctional proteases that not only cleave viral polyproteins during virus replication but also deubiquitinate cellular proteins to suppress ubiquitin (Ub)-mediated antiviral mechanisms. Here, we report an approach to attenuate the infection of Arabidopsis thaliana by Turnip Yellow Mosaic Virus (TYMV) by suppressing the polyprotein cleavage and deubiquitination activities of the TYMV protease (PRO). Performing selections using a library of phage-displayed Ub variants (UbVs) for binding to recombinant PRO yielded several UbVs that bound the viral protease with nanomolar affinities and blocked its function.

Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer.

This study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, and bi-dimensional projection experiments. DFT experiments was utilized also to study the structural and electrostatic properties of T-1-NBAB.

Stereoselective Sequential Diels-Alder Reactions on a Cyclic Furan Trimer for the Construction of an Asymmetric Scaffold.

Multiple Diels-Alder reactions are a powerful method to construct large asymmetric scaffolds, but these reactions often produce numerous isomers. We now report a triple Diels-Alder reaction between a cyclic furan trimer and -substituted maleimides, achieving selective synthesis of a single asymmetric tris-adduct. The stereoselectivity of cycloaddition to π-extended furan derivatives was clarified by the experimental analysis of intermediates and theoretical calculations.

Deep learning based analysis of G3BP1 protein expression to predict the prognosis of nasopharyngeal carcinoma.

Background: Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) emerges as a pivotal oncogenic gene across various malignancies, notably including nasopharyngeal carcinoma (NPC). The use of automated image analysis tools for immunohistochemical (IHC) staining of particular proteins is highly beneficial, as it could reduce the burden on pathologists. Interestingly, there have been no prior studies that have examined G3BP1 IHC staining using digital pathology.

Identification of key regulators in pancreatic ductal adenocarcinoma using network theoretical approach.

Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease with poor clinical outcomes, which is mainly because of delayed disease detection, resistance to chemotherapy, and lack of specific targeted therapies. The disease's development involves complex interactions among immunological, genetic, and environmental factors, yet its molecular mechanism remains elusive. A major challenge in understanding PDAC etiology lies in unraveling the genetic profiling that governs the PDAC network.

Metabolomic analysis of murine tissues infected with Brucella melitensis.

Brucella is a gram negative, facultative intracellular bacterial pathogen that constitutes a substantial threat to human and animal health. Brucella can replicate in a variety of tissues and can induce immune responses that alter host metabolite availability. Here, mice were infected with B.

Multicomponent Electrosynthesis of Enaminyl Sulfonates Starting from Alkylamines, SO, and Alcohols.

An electrochemical one-pot synthesis of enaminyl sulfonate esters was established, featuring a quasidivided cell under constant current conditions. The multicomponent reaction utilizes simple and readily available alkylamines and an easy-to-use stock solution of SO and alcohols. Omission of additional supporting electrolyte through in-situ-generated monoalkylsulfite facilitates the downstream processing.

Intramolecular Fluoroacylation Enabled by TrBF-Catalyzed Fluoride Recycling.

Alkyne- and alkene-tethered acyl fluorides undergo intramolecular carbofluorination via fluoride recycling using catalytic TrBF. Excellent stereoselectivity is observed for the alkyne addition, enabling access to novel fluorinated indan-2-ones (all ≥95:5 /) and cyclopentan-2-ones (85:15 /). Fluorinated chroman-2-ones and tertiary alkyl fluorides can also be synthesized using this method, comparing favorably to previously reported protocols that employ expensive metal catalysts under harsher conditions.