A dual-strategy approach to improve GS-441524 therapy in feline infectious peritonitis: salt engineering and orally disintegrating tablet development.

Feline infectious peritonitis (FIP) is a fatal disease caused by mutations in feline enteric coronavirus, posing significant challenges in feline medicine. GS-441524 (GS), the active metabolite of remdesivir, has demonstrated efficacy in FIP treatment. However, its poor solubility and low oral bioavailability require high doses for therapeutic effect, limiting its practicality.

Electrochemical Aerobic Oxidation and Cyclization of 2-Alkylbenzamides toward 3-Hydroxyisoindolinones.

In this study, we present an electrochemical method for forming C(sp)-N and C(sp)-O bonds from 2-alkylbenzamides, leading to the synthesis of 3-hydroxyisoindolinones. This reaction demonstrates broad substrate compatibility and can efficiently transform 2-alkylbenzamides with primary and secondary C(sp)-H bonds by using -BuNBr under open-air conditions. The proposed methodology provides a straightforward, efficient, and atom-economical route to access diverse 3-hydroxyisoindolinones (28 examples, up to 82% yield).

Tumor-specific biochemical nanoconversion of self-assembled peptide-conjugated paclitaxel-docetaxel-based nanoparticles.

Docetaxel (DTX, 1) and paclitaxel (PTX, 2) are famous cytotoxic agents widely used in cancer therapy, however, their low specificity for tumor cells often results in severe systemic toxicity. Beyond conventional prodrug strategies, this study introduces a novel nanoconversion technology that chemically modifies DTX to form self-assembled nanoparticles (NPs), which subsequently convert into a paclitaxel-mimicking molecule (PTXm, 3). Hydrophilic acetylated Phe-Arg-Arg-Phe peptide ((Ac)FRRF, 4) and hydrophobic docetaxel were conjugated to prepare self-assembled (Ac)FRRF-DTX NPs.

Nanoporous amorphous carbon nanopillars with lightweight, ultrahigh strength, large fracture strain, and high damping capability.

Simultaneous achievement of lightweight, ultrahigh strength, large fracture strain, and high damping capability is challenging because some of these mechanical properties are mutually exclusive. Here, we utilize self-assembled polymeric carbon precursor materials in combination with scalable nano-imprinting lithography to produce nanoporous carbon nanopillars. Remarkably, nanoporosity induced via sacrificial template significantly reduces the mass density of amorphous carbon to 0.

Annulation of -silyl ,-ketene acetals with alkynes for the synthesis of dihydropyridinones and its application in concise total synthesis of phenanthroindolizidine alkaloids.

The formation of -heterocycles with multiple substituents is important in organic synthesis. Herein, we report a novel method for the construction of functionalized dihydropyridinone rings through the annulation of an amide -carbon with a tethered alkyne moiety. The reaction of the amide with the alkyne was achieved via -silyl ,-ketene acetal formation and silver-mediated addition.

Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis.

IL-31RA and TRPV1 Expression in Atopic Dermatitis Induced with Trinitrochlorobenzene in Nc/Nga Mice.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Interleukin 31 (IL-31), a novel cytokine in AD, causes pruritus, typically characteristic of AD patients. The transient receptor potential vanilloid type 1 (TRPV1) is a cation channel activated by diverse noxious stimuli that has been studied in a variety of pruritic skin diseases.

Sialic acid-decorated liposomes enhance the anti-cancer efficacy of docetaxel in tumor-associated macrophages.

Tumor-associated macrophages (TAMs) in the tumor microenvironment potentially enhance tumor growth and invasion through various mechanisms and are thus an essential factor in tumor immunity. The highly expressed siglec-1 receptors on the surfaces of TAMs are potential targets for cancer drug delivery systems. Sialic acid (SA) is a specific ligand for siglec-1.

Doxorubicin covalently conjugated heparin displays anti-cancer activity as a self-assembled nanoparticle with a low-anticoagulant effect.

Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti-inflammatory therapy beyond its anticoagulant effect. Here, we sought to utilize heparin molecules as drug carriers by directly conjugating the anticancer drug doxorubicin to the carboxyl group of unfractionated heparin.

Prediction of Cancer Metastasis Using Correlations Between miRNAs and Competing Endogenous RNAs.

Cancer metastasis is a complex process which involves the spread of tumor cells from the primary site to other parts of the body. Metastasis is the major cause of cancer mortality, accounting for about 90% of cancer deaths. Metastasis is primarily diagnosed by clinical examinations and imaging techniques, but such a diagnosis is made after metastasis has occurred.

Finding miRNA-RNA Network Biomarkers for Predicting Metastasis and Prognosis in Cancer.

Despite remarkable progress in cancer research and treatment over the past decades, cancer ranks as a leading cause of death worldwide. In particular, metastasis is the major cause of cancer deaths. After an extensive analysis of miRNAs and RNAs in tumor tissue samples, we derived miRNA-RNA pairs with substantially different correlations from those in normal tissue samples.

Lysosomal lipid peroxidation regulates tumor immunity.

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity.

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic-DEVD-Doxorubicin Conjugate for Targeted Cancer Therapy.

In the development of new drugs, typical polymer- or macromolecule-based nanocarriers suffer from manufacturing process complexity, unwanted systematic toxicity, and low loading capacity. However, carrier-free nanomedicines have made outstanding progress in drug delivery and pharmacokinetics, demonstrating most of the advantages associated with nanoparticles when applied in targeted anticancer therapy. Here, to overcome the problems of nanocarriers and conventional cytotoxic drugs, we developed a novel, carrier-free, self-assembled prodrug consisting of a hydrophobic palmitic (16-carbon chain -hexadecane chain) moiety and hydrophilic group (or moiety) which is included in a caspase-3-specific cleavable peptide (Asp-Glu-Val-Asp, DEVD) and a cytotoxic drug (doxorubicin, DOX).

Facile One-Pot Synthesis of Polysubstituted Pyridinium Salts by Annulation of Enamines with Alkynes.

An efficient and facile synthesis of highly substituted pyridinium salts through the annulation of enamines with alkynes is reported herein. A Ag CO /HNTf synergistically acting catalyst system was developed and used in a condensation reaction between carbonyl substrates and propargylamine to afford structurally diverse pyridinium salts. A mechanistic investigation shows that this one-pot transformation proceeded via selective 6-endo-dig cyclization of the in situ generated propargylenamine and protonolysis of the resulting vinyl-silver intermediate.

Constructing Integrative ceRNA Networks and Finding Prognostic Biomarkers in Renal Cell Carcinoma.

Inspired by a newly discovered gene regulation mechanism known as competing endogenous RNA (ceRNA) interactions, several computational methods have been proposed to generate ceRNA networks. However, most of these methods have focused on deriving restricted types of ceRNA interactions such as lncRNA-miRNA-mRNA interactions. Competition for miRNA-binding occurs not only between lncRNAs and mRNAs but also between lncRNAs or between mRNAs.

Evolution of a Strategy for Concise Enantioselective Total Synthesis of the Salinosporamide Family of Natural Products.

Our first strategy for rapidly accessing pyrrolidinone cores of salinosporamides involved combined use of memory of chirality and dynamic kinetic resolution principles in aldol reactions of the serine-derived 5-oxazolidinone substrate, which was ultimately unsuccessful with respect to enantioselectivity. This failure led us to the revised strategy. The influence of the stereocenter in 5-oxazolidinone enabled selective installation of the C-2 stereocenter.

Association between oral health and frailty: results from the Korea National Health and Nutrition Examination Survey.

Background: Previous research has suggested that poor oral health is positively associated with frailty. The objective of this study was to explore associations of key oral diseases (periodontal disease, tooth loss), and oral hygiene and management behaviors with the level of frailty in community-dwelling older Korean adults using national representative survey data.

Methods: This study used cross-sectional, 6th and 7th Korea National Health and Nutrition Examination Survey (KNHANES VI, VII) data.

Constructing a Cancer Patient-Specific Network Based on Second-Order Partial Correlations of Gene Expression and DNA Methylation.

Typically patient-specific gene networks are constructed with gene expression data only. Such networks cannot distinguish direct gene interactions from indirect interactions via others such as the effect of epigenetic events to gene activity. There is an increasing evidence of inter-individual variations not only in gene expression but also in epigenetic events such as DNA methylation.

Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits.

More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Here, we have demonstrated that a biodegradable piezoelectric poly(L-lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration.

Cation Composition-Dependent Device Performance and Positive Bias Instability of Self-Aligned Oxide Semiconductor Thin-Film Transistors: Including Oxygen and Hydrogen Effect.

Amorphous oxide semiconductor transistors control the illuminance of pixels in an ecosystem of displays from large-screen TVs to wearable devices. To satisfy application-specific requirements, oxide semiconductor transistors of various cation compositions have been explored. However, a comprehensive study has not been carried out where the influence of cation composition, oxygen, and hydrogen on device characteristics and stability is systematically quantified, using commercial-grade process technology.

Clinical and immunohistochemical findings of splenic mast cell tumour in a cat: A case report.

A 6-year-old, spayed, female, domestic shorthair cat presented with a 4-month history of chronic intermittent vomiting and anorexia. The haematologic results indicated moderate anaemia and a circulating mast cell population. The abdominal radiography revealed a markedly enlarged spleen.

Synthesis of Bridged Oxabicycles via Cascade Reactions involving -Acyloxocarbenium Ion Intermediates.

Compared to related electrophilic species, -acyloxocarbenium ions (AOIs) have been much less utilized in organic synthesis due to the lack of an efficient formation method. Here, we present a facile and simple approach for the generation of AOI from ester and acetal groups. Based on our AOI system with a pendant nucleophile, we obtained a unique bridged bicyclic system via an epoxonium-like transition state.

Pseudoelasticity of SrNiP Micropillar via Double Lattice Collapse and Expansion.

The maximum recoverable strain of most crystalline solids is less than 1% because plastic deformation or fracture usually occurs at a small strain. In this work, we show that a SrNiP micropillar exhibits pseudoelasticity with a large maximum recoverable strain of ∼14% under uniaxial compression via unique reversible structural transformation, double lattice collapse-expansion that is repeatable under cyclic loading. Its high yield strength (∼3.

Memory of Chirality in the Asymmetric Synthesis of Piperidines with Vicinal Stereocenters by Intramolecular Sn2' Reaction.

Intramolecular Sn2' cyclization of α-amino ester enolates provided piperidine derivatives with vicinal quaternary-tertiary stereocenters with excellent diastereo- and enantioselectivity via memory of chirality and the Thorpe-Ingold effect. DFT calculations provided a mechanistic rationale for the increase in chirality preservation via the Thorpe-Ingold effect. This new method has the potential to be integrated into concise asymmetric synthesis of bioactive molecules containing multisubstituted piperidine moieties.

Targeted delivery of mPGES-1 inhibitors to macrophages via the folate receptor-β for inflammatory pain.

Activated macrophages overexpress the folate receptor β (FR-β) that can be used for targeted delivery of drugs conjugated to folic acid. FR-expressing macrophages contribute to arthritis progression by secreting prostaglandin E (PGE). Non-steroidal anti-inflammatory drugs (NSAIDs) block PGs and thromboxane by inhibiting the cyclooxygenase (COX) enzymes and are used for chronic pain and inflammation despite their well-known toxicity.