Developing a psychological care competences framework for nurses in China: a mixed methods study.

BACKGROUND: With social transformation, rapid economic development and deepening awareness of psychological health in China, people's demand for psychological health services is becoming increasingly urgent. A key challenge for Chinese medical organizations is to train enough qualified psychological care nurses. A greater understanding of psychological care competences (PCC) can help in clinical nurse selection, training, and assessment. OBJECTIVE: To develop a PCC framework for Chinese nurses and obtain a consensus on the framework among experts. METHODS: A descriptive mixed methods study was designed consisting of a literature review and semi-structured interviews followed by three Delphi rounds. The experts (n = 16) involved were nurses, nursing managers and educators from nine Chinese provinces with a specific interest in psychological care. Descriptive statistics assisted in data analysis. RESULTS: Using the Iceberg Model as a theoretical foundation, five main dimensions and associated subdomains were integrated from 39 chosen articles. The semi-structured interviews with 24 nursing managers and nurses confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the initial PCC framework. After three Delphi rounds, the experts reached consensus on the PCC framework, including five domains (knowledge, skills, professional ethics, personal traits, internal motivations) and 22 subdomains with connotations. The response rate (RR) values for the three rounds of consultation were 80.00%, 87.50% and 92.86%, the composite reliability (Cr) values were 0.89-0.90, and the Kendall coordination coefficients were 0.155-0.200 (P < 0.05). CONCLUSIONS: On the basis of the Iceberg Model, literature review and qualitative research methods along with Delphi technique were used to develop a scientific and systematic PCC framework. The research methods were feasible and the results were reliable, thereby providing a basis for adopting this framework into nursing education. A formal assessment tool should be developed to test the PCC of nurses in clinical practice.

Synthesis and Properties of the Novel High-Performance Hydroxyl-Terminated Liquid Fluoroelastomer.

Functional liquid fluoroelastomers are in high demand in new energy fields. And these materials have potential applications in high-performance sealing materials and as electrode materials. In this study, a novel high-performance hydroxyl-terminated liquid fluoroelastomer (t-HTLF) with a high fluorine content, temperature resistance, and curing efficiency was synthesised from a terpolymer of vinylidene fluoride (VDF), tetrafluoroethylene (TFE), and hexafluoropylene (HFP). A carboxyl-terminated liquid fluoroelastomer (t-CTLF) with controllable molar mass and end-group content was first prepared from a poly(VDF-ter-TFE-ter-HFP) terpolymer using a unique oxidative degradation method. Subsequently, an efficient "one-step" reduction of the carboxyl groups (COOH) in t-CTLF into hydroxyl groups (OH) was achieved via the functional-group conversion method using lithium aluminium hydride (LiAlH4) as the reductant. Thus, t-HTLF with a controllable molar mass and end-group content and highly active end groups was synthesised. Owing to the efficient curing reaction between OH and isocyanate groups (NCO), the cured t-HTLF exhibits good surface properties, thermal properties, and chemical stability. The thermal decomposition temperature (Td) of the cured t-HTLF reaches 334 °C, and it exhibits hydrophobicity. The oxidative degradation, reduction, and curing reaction mechanisms were also determined. The effects of solvent dosage, reaction temperature, reaction time, and ratio of the reductant to the COOH content on the carboxyl conversion were also systematically investigated. An efficient reduction system comprising LiAlH4 can not only achieve an efficient conversion of the COOH groups in t-CTLF to OH groups but also the in situ hydrogenation and addition reactions of residual double bonds (C=C) groups in the chain, such that the thermal stability and terminal activity of the product are improved while maintaining a high fluorine content.

The high burden of symptoms associated with cognitive impairment in lung cancer patients: A latent class analysis.

Objective: To explore the association between the pain-fatigue-sleep disturbance-depression symptom cluster (SC) and cancer-related cognitive impairment (CRCI) in patients having lung cancer and to identify other factors influencing CRCI. Methods: A cross-sectional study was conducted to investigate 378 patients having lung cancer in China from October 2021 to July 2022. The perceived cognitive impairment scale and the general anxiety disorder-7 were used to assess patients' cognitive impairment and anxiety, respectively. The pain-fatigue-sleep disturbance-depression SC was assessed with the brief fatigue inventory, the brief pain inventory, the Patient Health Questionnaire-9, and the Athens Insomnia Scale. Latent class analysis by Mplus.7.4 was used to identify latent classes of the SC. We adjusted for covariates in the multivariable logistic regression model to examine the relationship between the pain-fatigue-sleep disturbance-depression SC and CRCI. Results: Among patients having lung cancer, two SC classes were identified: high and low symptom burden groups. In the crude model, compared to the low symptom burden group, the high symptom group had greater odds of developing CRCI (odds ratio: 10.065, 95% confidence interval: 4.138-24.478). After adjusting for covariates, in model 1, the high symptom group still had greater odds of developing CRCI (odds ratio: 5.531, 95% confidence interval: 2.133-14.336). Additionally, a diagnosis of over 6 months, anxiety, leisure activity, and a high platelet-to-lymphocyte ratio were found to be influencing factors of CRCI (all P â€‹< â€‹0.05). Conclusions: Our study revealed that a high symptom burden is a significant risk factor for CRCI, which may provide a new perspective for managing CRCI in lung patients having cancer.

Research Progress on Two-Dimensional Layered MXene/Elastomer Nanocomposites.

Two-dimensional (2D) transition-metal carbon/nitrogen/carbon nitride (MXene) has extremely high conductivity and easily modifiable surface functional groups. Compared with graphene, another 2D layered material, MXene is easily dispersed in water owing to its hydrophilic groups. Its unique characteristics make MXene a valuable material. Nanocomposites can be endowed with functionality when MXene is compounded with an elastomer. Particularly in electromagnetic interference shielding and sensing, MXene exhibits extraordinary properties. We review various preparation methods, properties, and applications of MXene and MXene/elastomer nanocomposites and present a summary of the prospects for MXene/elastomer nanocomposites, which are in their initial stage of development and providing promising results.

Structure, preparation and properties of liquid fluoroelastomers with different end groups.

In order to design and prepare liquid fluoroelastomers with different end groups, and reveal the relationship between the molecular chain structure and properties, we studied on the oxidation degradation method and functional group conversion method to prepare carboxyl-terminated and hydroxyl-terminated liquid fluoroelastomers, respectively. The reaction mechanisms were also deduced. Furthermore, the curing system was created for liquid fluoroelastomers, and systematically analyzed their properties. The sequence type and content of the -C[double bond, length as m-dash]C- and oxygen-containing groups in the samples were measured and characterized by attenuated total reflectance/Fourier transform infrared (ATR-FTIR) spectroscopy, 1H nuclear magnetic resonance (1H-NMR), 19F-NMR spectroscopy and chemical titration, the molecular weights of liquid fluoroelastomers were measured by gel permeation chromatography (GPC). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to examine the thermal properties, while a viscometer was used to measure the dynamic viscosity of the liquid fluoroelastomers. Then the mechanical and surface properties of the cured samples were examined by universal testing machine and contact angle measurement instrument, respectively. The results show that carboxyl-terminated liquid fluoroelastomer with 2.71 wt% carboxyl terminal groups can be prepared by oxidation degradation method. When lithium aluminium hydride (LiAlH4) was used as the reducing agent, it can efficiently convert carboxyl group to hydroxyl group with a conversion rate of more than 95%. In addition, it can be seen that the dynamic viscosity of the liquid fluoroelastomers were all decreased with the increase of temperature, and it is similar to about 10 Pa s at 70 °C. Compared with carboxyl-terminated liquid fluoroelastomers, hydroxyl-terminated liquid fluoroelastomers has higher curing reactivity, higher glass transition temperature (T g) and thermal decomposition temperature (T d), and better mechanical properties of cured samples. The two types of liquid fluoroelastomers with distinct end groups presented distinct hydrophilicity.

Bio-Based Eucommia ulmoides Gum Composites with High Electromagnetic Interference Shielding Performance.

Herein, high-performance electromagnetic interference (EMI) shielding bio-based composites were prepared by using EUG (Eucommia ulmoides gum) with a crystalline structure as the matrix and carbon nanotube (CNT)/graphene nanoplatelet (GNP) hybrids as the conductive fillers. The morphology of the CNT/GNP hybrids in the CNT/GNP/EUG composites showed the uniform distribution of CNTs and GNPs in EUG, forming a denser filler network, which afforded improved conductivity and EMI shielding effect compared with pure EUG. Accordingly, EMI shielding effectiveness values of the CNT/GNP/EUG composites reached 42 dB in the X-band frequency range, meeting the EMI shielding requirements for commercial products. Electromagnetic waves were mainly absorbed via conduction losses, multiple reflections from interfaces and interfacial dipole relaxation losses. Moreover, the CNT/GNP/EUG composites exhibited attractive mechanical properties and high thermal stability. The combination of excellent EMI shielding performance and attractive mechanical properties render the as-prepared CNT/GNP/EUG composites attractive candidates for various applications.

Green Thermoplastic Vulcanizates Based on Silicone Rubber and Poly(butylene succinate) via In Situ Interfacial Compatibilization.

Presenting a combination of sustainability and environmental friendliness, a new class of green and non-petroleum-based thermoplastic vulcanizates (TPVs) was successfully developed from silica-filled silicone rubber (FSR) and poly(butylene succinate) (PBS) via dynamic vulcanization. The phase morphology, interfacial compatibilization, and microstructural properties of FSR/PBS TPVs were investigated. Notably, a large number of FSR microparticles were observed and were dispersed in the continuous PBS phase, indicating complete phase inversion during the dynamic vulcanization. The fine phase morphology of FSR/PBS TPVs was achieved by a fine phase morphology of the SR/PBS premix, the good interfacial compatibility between the PBS phase and the cross-linked FSR phase, and complete phase inversion. The as-prepared TPVs possessed high tensile strength, good elastic behavior, easy processability, and reprocessability. These novel non-petroleum-based TPVs have potential applications in packagings, biomedical devices, and three-dimensional (3D) printing materials.

Synthesis and characterization of biobased thermoplastic polyester elastomers containing Poly(butylene 2,5-furandicarboxylate).

A series of sustainable and reprocessible thermoplastic polyester elastomers P(BF-PBSS)s were synthesized using dimethyl-2,5-furandicarboxylate, 1,4-butanediol, and synthetic low-molecular-weight biobased polyester (PBSS). The P(BF-PBSS)s contain poly(butylene 2,5-furandicarboxylate) (PBF) as their hard segment and PBSS as their soft segment. The microstructures of the P(BF-PBSS)s were confirmed by nuclear magnetic resonance, demonstrating that a higher content of the soft segment was incorporated into P(BF-PBSS)s with higher PBSS content. Interestingly, dynamic mechanical analysis indicated that P(BF-PBSS)s comprised two domains: crystalline PBF and a mixture of amorphous PBF and PBSS. Consequently, the microphase separations of P(BF-PBSS)s were mainly induced by the crystallization of their PBF segments. More importantly, the thermal, crystallization, and mechanical properties could be tailored by tuning the PBSS content. Our results indicate that the as-prepared P(BF-PBSS)s are renewable, thermally stable, and nontoxic, and have good tensile properties, indicating that they could be potentially applied in biomedical materials.

Synthesis of a Carrageenan-Iron Complex and Its Effect on Flame Retardancy and Smoke Suppression for Waterborne Epoxy.

A k-carrageenan-iron complex (KC-Fe) was synthesized by complexation between degraded KC and FeCl3. Furthermore, KC-Fe and ammonium polyphosphate (APP) were simultaneously added into waterborne epoxy (EP) to improve its flame retardancy and smoke suppression performance. The structure and properties of KC-Fe were assessed using Fourier transform infrared spectroscopy (FTIR), ultraviolet (UV) spectroscopy, thermo gravimetric analysis (TGA), and X-ray powder diffraction analysis (XRD). The analysis showed that KC-Fe was successfully synthesized and exhibited good thermal properties with a 49% char residue at 800 °C. The enhanced flame retardancy and smoke suppression performance of waterborne epoxy were evaluated using a limiting oxygen index (LOI) and UL-94. Moreover, the flame retardancy of waterborne epoxy coated on a steel plate was also investigated using cone calorimetry. The results showed that the flame-retardant waterborne epoxy blend exhibited the best flame retardancy when the mass ratio of APP and KC-Fe was 2:1. The total heat release (THR) and total smoke production (TSP) was decreased by 44% and 45%, respectively, which indicated good fire safety performance and smoke suppression properties. Analysis of the residual char using FTIR, SEM, and elemental analysis (EDS) indicated that the action of KC-Fe was promoted by the presence of APP. The formation of a dense thermal stable char layer from an intumescent coating was essential to protect the underlying materials.

Awareness of risk factors and warning symptoms and attitude towards gastric cancer screening among the general public in China: a cross-sectional study.

OBJECTIVES: This study aimed to assess the knowledge of risk factors and warning symptoms and attitude towards gastric cancer screening among the general population in China. SETTING: Hunan province, China PARTICIPANTS: Individuals aged older than 18 years were recruited using a cluster sampling method. DESIGN: A cross-sectional study, and a pretested structured questionnaire was used to assess participants' awareness of gastric cancer. PRIMARY AND SECONDARY OUTCOME MEASURES: Knowledge level of risk factors and warning symptoms of gastric cancer, gastric cancer screening attitude, sociodemographic factors associated with gastric cancer knowledge and screening behaviour. RESULTS: This study comprised 1200 participants with a mean age of 40.31 (SD 16.73) years, of whom 622 (51.8%) were women. The mean score for gastric cancer knowledge was 8.85/22 (SD 6.48). There were 47.0% of the participants who had a low knowledge level about the risk factors and warning symptoms of gastric cancer. In total, 83.8% believed screening is helpful for early detection of gastric cancer, and 15.2% had undergone gastric cancer screening. The most common reason for not undergoing screening was having 'no symptoms' (63.0%), followed by 'fear of undergoing gastroscopy' (38.1%). Independent factors related to lower knowledge levels included male sex, living in rural areas, lower educational level, working as a farmer and without a family history of gastric cancer (p<0.05). Factors independently associated with screening behaviour included white-collar employment, higher income and having upper gastrointestinal tract diseases (p<0.05). CONCLUSIONS: In China, people have poor knowledge about risk factors and warning symptoms of gastric cancer, but a majority have a positive attitude towards the benefits of gastric cancer screening. Being asymptomatic and having a fear of gastroscopy were the main self-reported reasons for not undergoing screening. These results highlight the urgent need for educational campaigns to improve gastric cancer awareness.

Hot nitric acid diffusion in fluoroelastomer composite and its degradation.

Fluoroelastomers (FKM) are vital sealing materials in acidic environment and their failure can cause severe safety problems. Therefore, investigation of the degradation behavior and mechanism of FKM materials is of great significant. Herein, we investigate a diffusion model of an acidic solution into an FKM composite and its degradation behavior upon immersion in hot nitric acid solution. The results indicate that the diffusion process of the HNO3 solution into the FKM composite conforms to the Fick diffusion model at a low concentration of nitric acid solution. Besides, the concentration of HNO3 solution affects the diffusion process of solvent molecules and the dissolution process of the filler particles to some extent. SEM showed that the surface topography of the FKM was significantly altered after it was immersed in HNO3 solution. The structural and chemical changes of the FKM were studied using ATR-FTIR, SEM-EDS and MAS NMR, which demonstrated the occurrence of decrosslinking via hydrolysis of the crosslinks and backbone cleavage by dehydrofluorination. This was also manifested by the decrease in crosslinking degree and mechanical properties. The present study is helpful for revealing the chemical changes in FKM in hot HNO3 solution.

Synergistic Effect of Graphene Oxide and Mesoporous Structure on Flame Retardancy of Nature Rubber/IFR Composites.

Aiming to improve the flame retardancy performance of natural rubber (NR), we developed a novel flame retardant synergistic agent through grafting of MCM-41 to graphene oxide (GO), named as GO-NH-MCM-41, as an assistant to intumescent flame retardants (IFR). The flame retardancy of NR/IFR/GO-NH-MCM-41 composites was evaluated by limited oxygen index (LOI), UL-94, and cone calorimeter test. The LOI value of NR/IFR/GO-NH-MCM-41 reached 26.3%; the UL-94 ratings improved to a V-0 rating. Moreover, the addition of GO-NH-MCM-41 decreased the peak heat release rate (PHRR) and the total heat release (THR) of the natural rubber composites. Furthermore, the addition of GO-NH-MCM-41 increased the thickness of char residue. The images of SEM indicated the char residue was more compact and continuous. The degradation of GO-NH-MCM-41-based NR composites was completed with a mass loss of 35.57% at 600 °C. The tensile strength and the elongation at break of the NR/IFR/GO-NH-MCM-41 composites were 13.9 MPa and 496.7%, respectively. The results of the rubber process analyzer (RPA) reached the maximum value, probably due to a better network of fillers in the matrix.

Facile Synthesis and Down-Conversion Emission of RE3+-Doped Lutetium Oxide Nanoparticles.

Lu2O3:RE3+ (RE3+ = Eu3+, Tb3+, Ho3+) nanoparticles have been successfully synthesized by a facile homogeneous precipitation method with subsequent sintering process. The crystal structure, morphology and luminescence properties of the as-prepared samples have been characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), photoluminescence (PL) and cathodoluminescence (CL) spectra. Upon ultraviolet (UV) and low-voltage electron beam excitation, Lu2O3:RE3+ (RE3+ = Eu3+, Tb3+, Ho3+) nanoparticles show strong red (Eu3+,5D0 → 7F2), green (Tb3+,5D4 → 7F5), and green (Ho3+,5S2 → 5I8) emissions. They exhibit a good advantage of multicolor emissions in the visible region, and endow these kinds of materials with potential application in many fields, such as light display systems, optoelectronic devices and biological imaging.

An environmentally sustainable plasticizer toughened polylactide.

Cardanol (CD), derived from renewable natural cashew nutshell liquid, has been used as a new plasticizer for polylactide (PLA), to create blends which retain the environmentally friendly features of PLA. The differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM) results all reveal that PLA and CD show good miscibility at low CD content. CD significantly decreased the glass transition temperature and enhanced the crystallization ability of PLA, demonstrating good plasticizing efficiency with PLA. At 10 wt% CD, ultimate elongation and impact toughness increased to 472% and 9.4 kJ m-2, respectively, which represented improvements of 31-fold and 2.6-fold over the corresponding measurements for neat PLA. The plasticization effect of CD was also demonstrated by the decreased melt complex viscosity and shear storage modulus at lower CD content for the blends when compared with neat PLA. Thus, the investigated CD presents an interesting candidate for a PLA plasticizer, meeting "double green" criteria. No cytotoxicity was found for the blends and hence they may be suitable for biomedical applications.

Facile synthesis of monodisperse LuPO4:Eu3+/Tb3+ hollow nanospheres and their luminescence properties.

Highly uniform and well-dispersed LuPO4 hollow nanospheres were successfully synthesized via a facile solution-phase method by utilizing the colloidal spheres of Lu(OH)CO3 as a sacrificial template and NH4H2PO4 as a phosphorus source. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transformed infrared (FT-IR), photoluminescence (PL) spectra, and cathodoluminescence (CL) spectra were employed to characterize the samples. The result indicates that the hollow LuPO4 spheres can be indexed to the tetragonal phase. The hollow LuPO4 spheres with diameter of about 300 nm become larger with respect to the sacrificial template. The shell of the hollow microspheres consists of numerous nanorods with the thickness of approximately 10 nm. Moreover, the possible formation mechanism of the evolution from Lu(OH)CO3 spheres to the final hollow LuPO4 hollow spheres has been proposed. In addition, upom ultraviolet (UV) and low-voltage electron beams excitation, 5 mol% Eu3+ and 5 mol% Tb3+ doped LuPO4 samples exhibit strong orange-red and green emission, corresponding to the characteristic lines of Eu3+ and Tb3+ under UV excitation, respectively, which may find potential application in the fields of color display and biomedicine.

Facile fabrication and photoluminescence properties of rare-earth-doped Gd2O3 hollow spheres via a sacrificial template method.

Rare-earth-doped gadolinium oxide (Gd2O3) hollow spheres were successfully fabricated on a large scale by using PS spheres as sacrificed templates and urea as a precipitating agent, which involved the deposition of an inorganic coating Gd(OH)CO3 on the surface of PS spheres and subsequent calcination in the air. Various approaches including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), thermogravimetric and differential thermal analysis (TG-DTA), as well as photoluminescence spectroscopies were used to characterize the samples. The results indicate that the sample is composed of uniform hollow Gd2O3 spheres with a mean particle size of about 2.3 µm and these hollow spheres have the mesoporous shell that are composed of a large amount of nanoparticles. The possible mechanism of evolution from PS spheres to the amorphous precursor and to the final hollow Gd2O3 spheres have been proposed. The as-obtained samples show strong light emission with different colors corresponding to different Ln³âº ions under ultraviolet-visible light and electron-beam excitation. Under 980 nm NIR irradiation, Gd2O3:Ln³âº (Ln³âº = Yb³âº/Er³âº, Yb³âº/Tm³âº and Yb³âº/Ho³âº) exhibit characteristic up-conversion (UC) emissions of red (Er³âº, ²H11/2, 4S3/2, 4F9/2 → 4I15/2), blue (Tm³âº, ¹G4 → ³H6) and green (Ho³âº, 5F4, 5S2 → 5I8), respectively. These merits of multicolor emissions in the visible region endow these kinds of materials with potential applications in the field of light display systems, lasers, optoelectronic devices, and MRI contrast agents.

Comparing the acceptor promiscuity of a Rosa hybrida glucosyltransferase RhGT1 and an engineered microbial glucosyltransferase OleD(PSA) toward a small flavonoid library.

Glycosylation is a widespread modification of plant secondary metabolites, and catalyzed by a superfamily of enzymes called UDP-glycosyltransferases (UGTs). UGTs are often involved in late biosynthetic steps and show broad substrate specificity or regioselectivity. In this study, the acceptor promiscuity of a Rosa hybrid UGT RhGT1 and an evolved microbial UGT OleD(PSA) toward a small flavonoid library was probed and compared. Interestingly, RhGT1 showed comparable acceptor promiscuity in comparison with OleD(PSA), though the acceptor binding pocket of the latter is much more open and large. This clearly indicates that stabilization of the acceptor position by suitable hydrophobic interactions is important for the specificity or regioselectivity determination as well as overall fit of the acceptor into a 'big enough' binding pocket. This also poses a challenge for structure-based UGT engineering to alter the glucosylation pattern of flavonoids.

Synthesis of flavonol 3-O-glycoside by UGT78D1.

Glycosylation is an important method for the structural modification of various flavonols, resulting in the glycosides with increased solubility, stability and bioavailability compared with the corresponding aglycone. From the physiological point of view, glycosylation of plant flavonoids is of importance and interest. However, it is notoriously complicated that flavonols such as quercetin, kaempferol and myricetin, are glucosylated regioselectively at the specific position by chemical method. Compared to the chemical method, enzymatic synthesis present several advantages, such as mild reaction condition, high stereo or region selectivity, no protection/deprotection and high yield. UGT78D1 is a flavonol-specific glycosyltransferase, responsible for transferring rhamnose or glucose to the 3-OH position in vitro. In this study, the activity of UGT78D1 was tested against 28 flavonoids acceptors using UDP-glucose as donor nucleoside in vitro, and 5 acceptors, quercetin, myricetin, kaempferol, fisetin and isorhamnetin, were discovered to be glucosylated at 3-OH position. Herein, the small-scale 3-O-glucosylated quercetin, kaempferol and myricetin were synthesized by UGT78D1 and their chemical structures were confirmed by (1)H and (13)C nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS).

Discovery and extensive in vitro evaluations of NK-HDAC-1: a chiral histone deacetylase inhibitor as a promising lead.

Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G. J. Med. Chem. 2008, 51, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.

Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry.

Novel bisaryl maleimide derivatives to mimic natural kinase inhibitors were prepared through click chemistry. A highly selective hit was discovered in a 124-kinase-assay, and docking studies revealed a π-π stacking interaction with the Phe67 at the P-loop of GSK-3ß kinase.