Selective Access to 4‑Substituted 2‑Aminothiazoles and 4‑Substituted 5-Thiocyano-2-aminothiazoles from Vinyl Azides and Potassium Thiocyanate Switched by Palladium and Iron Catalysts

A highly selective construction of 4-substituted 2-aminothiazoles and 4-substituted 5-thiocyano-2-aminothiazoles, respectively, catalyzed by palladium­(II) acetate and promoted by iron­(III) bromide from vinyl azides and potassium thiocyanate has been developed. Use of readily available starting materials, high selectivity, as well as mild reaction conditions make this practical method particularly attractive

One-pot three-component protocol for the synthesis of substituted 2-aminothiazoles

<p>Substituted 2-aminothiazoles have been synthesized from α-nitro-epoxides, cyanamide, and sodium sulfide through a facile, three-component, and ecofriendly protocol with good to excellent yields. This reaction was achieved at room temperature without any additives. A possible mechanism has also been proposed.</p

Table_1_Real-world national trends and socio-economic factors preference of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in China.docx

BackgroundsRobust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China.MethodA total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics.ResultsAnnual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency.ConclusionsSGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.</p

Parallel Control over Surface Charge and Wettability Using Polyelectrolyte Architecture: Effect on Protein Adsorption and Cell Adhesion

Surface charge and wettability, the two prominent physical factors governing protein adsorption and cell adhesion, have been extensively investigated in the literature. However, a comparison between these driving forces in terms of their independent and cooperative effects in affecting adhesion is rarely explored on a systematic and quantitative level. Herein, we formulate a protocol that features two-dimensional control over both surface charge and wettability with limited cross-parameter influence. This strategy is implemented by controlling both the polyion charge density in the layer-by-layer (LbL) assembly process and the polyion side-chain chemical structures. The 2D property matrix spans surface isoelectric points ranging from 5 to 9 and water contact angles from 35 to 70°, with other interferential factors (e.g., roughness) eliminated. The interplay between these two surface variables influences protein (bovine serum albumin, lysozyme) adsorption and 3T3 fibroblast cell adhesion. For proteins, we observe the presence of thresholds for surface wettability and electrostatic driving forces necessary to affect adhesion. Beyond these thresholds, the individual effects of electrostatic forces and wettability are observed. For fibroblast, both surface charge and wettability have an effect on its adhesion. The combined effects of positive charge and hydrophilicity lead to the highest cell adhesion, whereas negative charge and hydrophobicity lead to the lowest cell adhesion. Our design strategy can potentially form the basis for studying the distinct behaviors of electrostatic force or wettability driven interfacial phenomena and serve as a reference in future studies assessing protein adsorption and cell adhesion to surfaces with known charge and wettability within the property range studied here

Additional file 4 of Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

Additional file 4: Figure S1. The mRNA level of NRK in WPMY-1 cells with or without siNRK. Figure S2. The mRNA level of NRK in BPH-1 cells with or without NRK overexpression. Figure S3. The expression level of NRK in prostatic stromal and epithelial cells. Figure S4. The IHC staining of NRK in TMA. The scale bar is 2 mm. Figure S5. Correlation analysis between the protein expression level of NRK and clinical characters of BPH patients

Additional file 1 of Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

Additional file 1: Table S1. List of primary antibodies

Additional file 2 of Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

Additional file 2: Table S2. List of siRNA sequences

Additional file 3 of Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

Additional file 3: Table S3. Primer sequences used to amplify target genes in human by PCR

Polymeric Nanoparticles Enhance the Ability of Deferoxamine To Deplete Hepatic and Systemic Iron

Chelators are commonly used to remove excess iron in iron-loading disorders. Deferoxamine (DFO) is an effective and safe iron chelator but an onerous parenteral administration regimen limits its routine use. To develop more effective methods for delivering iron chelators, we examined whether amphiphilic copolymer nanoparticles (NPs) could deliver DFO more efficiently. Physical characterization showed a uniform and stable preparation of DFO nanoparticles (DFO-NPs) with an average diameter of 105.3 nm. In macrophage (RAW264.7) and hepatoma (HepG2) cell lines, DFO-NPs proved more effective at depleting iron than free DFO. In wild-type mice previously loaded with iron dextran, as well as <i>Hbb</i>^{<i>th</i>3<i>/+</i>} and <i>Hfe</i>^{<i>–/–</i>} mice, which are predisposed to iron loading, DFO-NPs (40 mg/kg DFO; alternate days; 4 weeks) reduced hepatic iron levels by 71, 46, and 37%, respectively, whereas the equivalent values for free DFO were 53, 7, and 15%. Staining for tissue iron and urinary iron excretion confirmed these findings. Pharmacokinetic analysis showed that NP-encapsulated DFO had a much longer elimination half-life than free DFO (48.63 ± 28.80 vs 1.46 ± 0.59 h), and that DFO-NPs could be readily taken up by tissues and in particular by hepatic Kupffer cells. In vitro, DFO-NPs were less toxic to several cell lines than free DFO, and in vivo they did not elicit any specific inflammatory responses or histological changes. Our results suggest that using a nanoformulation of DFO is a valuable strategy for improving its efficiency as an iron chelator and that this could broaden its clinical use for the treatment of human iron overload disorders

Organoselenium Compounds Modulate Extracellular Redox by Induction of Extracellular Cysteine and Cell Surface Thioredoxin Reductase

The effect of selenium compounds on extracellular redox modulating capacity was studied in murine macrophage RAW 264.7 cells and differentiated human THP-1 monocytes. The arylselenium compounds benzeneselenol (PhSeH), dibenzyl diselenide (DBDSe), diphenyl diselenide (DPDSe), and ebselen were capable of inducing extracellular cysteine accumulation via a cystine- and glucose-dependent process. Extracellular cysteine production was dose-dependently inhibited by glutamate, an inhibitor of cystine/glutamate antiporter (<i>X</i>_c^– transporter), supporting the involvement of <i>X</i>_c^– transporter for cystine uptake in the above process. These arylselenium compounds also induced cellular thioredoxin reductase (TrxR) expression, particularly at the exofacial surface of cells. TrxR1 knockdown using small interfering RNA attenuated TrxR increases and cysteine efflux induced in cells by DPDSe. Sodium selenite (Na₂SeO₃), selenomethionine (SeMet), seleno-l-cystine (SeCySS), and <i>Se</i>-methylselenocysteine (MeSeCys) did not have these effects on macrophages under the same treatment conditions. The effects of organoselenium compounds on extracellular redox may contribute to the known, but inadequately understood, biological effects of selenium compounds