Analysis of the inhibitory effect of a refined human resources salary system on job transfer and transfer tendency of nurses.

To evaluate the impact of a refined human resources salary system on job transfer and transfer tendency. From January 2019 to December 2019, a refined human resources salary system reform was implemented at the Tangshan Workers' Hospital in Hebei Province, and the job transfer and transfer tendency of clinical nurses was assessed using the nurse job transfer tendency scale before and 1 year after the intervention. A total of 640 nurses completed the intervention and evaluation. The results showed that the job transfer rate following the intervention reduced to 0.22%. The total score of clinical nurse job transfer tendency was (10.80 ±â€…3.23) before the intervention and (9.66 ±â€…3.58) after 1 year of intervention, which was substantially lower (P < .001). The satisfaction scores of nurses on performance-based salary increased significantly from (67.83 ±â€…18.54) before the intervention to (80.66 ±â€…15.87) after intervention, with varying degrees of increase observed in each dimension (P < .001). The refined human resources salary system effectively reduced job transfer and transfer tendency of clinical nurses in hospital nursing management, and can be widely promoted and applied.

Tunable topological edge and corner states in an all-dielectric photonic crystal.

Topological photonics has become a new and fascinating area in recent years, which enables electromagnetic waves to propagate with negligible backscattering and excellent robustness even when encountering sharp corners or defects. But the flexible tunability of edge and corner states is challenging once the topological photonic crystals (PhCs) have been fabricated. In this paper, we propose a new all-dielectric PhC with C3 symmetry constructed by hexagonal array of petal-like aperture embedded in silicon background. The proposed configuration has much wider energy gap than its triangular counterpart, and hence is suitable for wideband and high-capacity applications. When the apertures are filled with liquid crystals (LCs), the topologically-protected edge and corner states can be regulated through changing the refractive index of the LCs under different bias voltages. Moreover, the robustness of topological protection of edge and corner states is further demonstrated. This is the first demonstration of LC based tunable valley higher-order photonic topological insulator. The tunability of the proposed topological PhCs may be beneficial for development of tunable optical waveguides, reconfigurable topological microcavities, and other intelligent topological optical/terahertz devices.

Synthesis and evaluation of the anti-inflammatory activity of novel 8-quinolinesulfonamide derivatives as TLR4/MD-2 inhibitors with efficacy in adjuvant-induced arthritis.

In this study, a series of 8-quinolinesulfonamidederivatives was synthesized, and their anti-inflammatory activity was evaluated. Among them, compound 3l was found to be the best anti-inflammatory agent, with IC50 values of 2.61 ± 0.39, 9.74 ± 0.85, and 12.71 ± 1.34 µM against NO, TNF-α and IL-1ß production respectively. And 3l could significantly prevent lipopolysaccharide (LPS)-induced expression of inflammatory mediators (iNOS and COX-2). Molecule docking results showed that 3l could bind to the LPS binding site of toll-like receptor 4 (TLR4)/MD-2, and 3l was then identified as TLR4/MD-2 inhibitor by co-immunoprecipitation (co-IP) and cellular thermal shift assay (CTESA). Preliminary mechanism studies indicated that 3l could prevent TLR4 from being activated by disrupting TLR4/MD-2 heterodimerization and TLR4 homodimerization, thereby blocking the activation of the NF-κB/MAPK signaling pathway. Furthermore, observation of rat foot swelling, joint pathology and serum inflammatory cytokine levels proved that compound 3l had a significant therapeutic effect on adjuvant-induced arthritis (AIA) in rats in vivo. These results indicated that compound 3l is a potential anti-inflammatory agent, from which more effective anti-inflammatory drugs could be developed.

Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease.

A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC50 = 0.28 ± 0.05 µM) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Aß self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu2+ and Zn2+. In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.

Design and synthesis of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives as novel GSK-3ß inhibitors and evaluation of their potential as multifunctional anti-Alzheimer agents.

Pleiotropic intervention has prominent advantages for complex pathomechanisms, such as Alzheimer's disease (AD). In this study, a series of novel 3-(4-pyridyl)-5-(4- sulfamido-phenyl)-1,2,4-oxadiazole derivatives were designed and synthesized following the multitarget-directed ligand-based strategy. All compounds were evaluated for glycogen synthase kinase 3ß (GSK-3ß) inhibition and antineuroinflammatory and neuroprotective activities. Given that abnormal glucose metabolism plays an important role in AD occurrence and development, the effects of all compounds on glucose consumption in HepG2 cells was evaluated. Compounds 5e and 10b showed good dual potency in GSK-3ß inhibition (IC50: 5e = 1.52 µM, 10b = 0.19 µM) and antineuroinflammatory potency (IC50: 5e = 0.47 ± 0.64 µM, 10b = 6.94 ± 2.33 µM). The effect of compound 10b on glucose consumption was higher than that of positive drug metformin. These compounds exerted a certain neuroprotective effect. Compound 10b dramatically reduced Aß-induced Tau hyperphosphorylation, thus inhibiting GSK-3ß at the cellular level. Notably, compounds 5e and 10b exhibited good inhibitory effects on the formation of intracellular reactive oxygen species (ROS). Moreover, these compounds displayed proper blood-brain barrier permeability and lacked neurotoxicity up to 50 µM concentration. Finally, in vivo experiments revealed that compound 10b improved cognitive impairment in scopolamine-induced mouse models. Results indicated that compound 10b deserves further study as a multifunctional lead compound.

Identification of novel CDK 9 inhibitors based on virtual screening, molecular dynamics simulation, and biological evaluation.

AIMS: Cyclin-dependent kinase 9 (CDK9) is a member of the CDK subfamily and plays a major role in the regulation of transcriptional elongation. It has attracted widespread attention as a therapeutic target for cancer. Here, we aimed to explore novel CDK 9 inhibitors by using a hybrid virtual screening strategy. MAIN METHODS: A hybrid virtual screening strategy was constructed with computer-aided drug design (CADD). First, compounds were filtered in accordance with Lipinski's rule of five and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Second, a 3D-QSAR pharmacophore model was built and used as a 3D query to screen the obtained hit compounds. Third, the hit compounds were subjected to molecular docking studies. Fourth, molecular dynamics (MD) simulations were performed on CDK9 in complex with the final hits to examine the structural stability. Finally, CDK9 kinase biochemical assay was performed to identify the biological activity of the hit compounds. KEY FINDINGS: Seven hit compounds were screened out. These hit compounds showed drug-like properties in accordance with Lipinski's rule of five and ADMET. Complexes involving the six hit compounds bound to CDK9 exhibited good structural stability in the MD simulation. Furthermore, these six hit compounds had strong inhibitory activity against CDK9 kinase. In particular, hit 3 showed the most promising activity with the percentage of 71%. SIGNIFICANCE: The six hit compounds may be promising novel CDK9 inhibitors, and the hybrid virtual screening strategy designed in this study provides an important reference for the design and synthesis of novel CDK9 inhibitors.

Design, synthesis, and biological evaluation of rutacecarpine derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease.

A series of 3-amino-substituted rutacecarpine derivatives were synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver-Burk plotting and molecular modeling illustrated that 6n bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CAS) of BuChE. Furthermore, 6n modulated Aß aggregation; chelated biometals; presented good absorption, distribution, metabolism, excretion, and toxicity properties; and showed remarkable neuroprotective activity. Previous research has shown that the optimized compound 6n has considerable potential for development as an MTDL for the treatment of AD.

An efficient algorithm for finding all possible input nodes for controlling complex networks.

Understanding structural controllability of a complex network requires to identify a Minimum Input nodes Set (MIS) of the network. Finding an MIS is known to be equivalent to computing a maximum matching of the network, where the unmatched nodes constitute an MIS. However, maximum matching is often not unique for a network, and finding all possible input nodes, the union of all MISs, may provide deep insights to the controllability of the network. Here we present an efficient enumerative algorithm for the problem. The main idea is to modify a maximum matching algorithm to make it efficient for finding all possible input nodes by computing only one MIS. The algorithm can also output a set of substituting nodes for each input node in the MIS, so that any node in the set can replace the latter. We rigorously proved the correctness of the new algorithm and evaluated its performance on synthetic and large real networks. The experimental results showed that the new algorithm ran several orders of magnitude faster than an existing method on large real networks.