Tyrosine kinase 2 inhibitors: Synthesis and applications in the treatment of autoimmune diseases.

Janus kinase (JAK), a class of non-receptor tyrosine kinases, are essential in modulating the cytokine signaling cascade of cytokines associated with immune responses. Despite their potential in the treatment of autoimmune diseases, JAK inhibitors are associated with safety concerns, regarding cytokine suppression and significant side effects. Tyrosine kinase 2 (TYK2), a prominent member of the JAK family, is central to the signaling of interleukins (ILs) and interferons (IFNs), such as IL-12, IL-23 and IFNs.

Top of tide: Nexus between organization agility, digital capability and top management support in SME digital transformation.

In the swiftly evolving business landscape, digital transformation (DT) has emerged as a crucial strategy for firms to gain a competitive edge. Despite the abundance of literature on DT in firms, there remains a dearth of empirical research that defines and analyzes crucial antecedents of small and medium-sized enterprises' (SMEs) DT from an internal perspective. To fill this research gap, this study examines the correlation between organizational agility and digital capability in cultivating SMEs' DT while also evaluating top management support as a moderating variable through the lens of internal factors of SMEs.

Development of a non-intercepting weak beam current measurement electronics for Heavy Ion Accelerator Facility in Lanzhou.

Non-destructive measurements of low-intensity charged particle beams are particularly challenging for beam diagnostics. At the Heavy Ion Accelerator Facility in Lanzhou (HIRFL), beams with weak currents below 1 µA are often provided for experiments. The detection of such low beam current is below the threshold of typical standard beam current transformers.

Exploring the processes and mechanisms by which nonprofit organizations orchestrate global innovation networks: A case study of the COVAX program.

In cocreating value with other organizations, nonprofit organizations may face multiple management challenges, posed by multistakeholder global innovation networks. Since these have not yet been systematically studied by academics, this study explores how nonprofit organizations can promote the cocreation of value in multistakeholder global innovation networks. Adopting a longitudinal single-case study approach from the perspective of network orchestration theory, this work deeply analyzes how nonprofit organizations can promote the evolution of the global innovation network of the COVID-19 vaccine under the COVAX program.

Fostering the Environmental Performance of Hotels in Pakistan: A Moderated Mediation Approach From the Perspective of Corporate Social Responsibility.

The Islamic Republic of Pakistan has been a mere victim of climate change in recent years. The country needs emergency measures at every level to mitigate environmental dilapidation. The role of enterprises in the country's environmental efforts is critical.

Development of a diagonal-cut type beam position monitor for the booster ring in the High Intensity Heavy-Ion Accelerator Facility project.

A diagonal-cut type beam position monitor (BPM) has been developed for the High Intensity Heavy-Ion Accelerator Facility (HIAF) project at the Institute of Modern Physics. Compared with other types of BPMs, the diagonal-cut type BPM has almost perfect position linearity, i.e.

Organoboron Compounds: Effective Antibacterial and Antiparasitic Agents.

The unique electron deficiency and coordination property of boron led to a wide range of applications in chemistry, energy research, materials science and the life sciences. The use of boron-containing compounds as pharmaceutical agents has a long history, and recent developments have produced encouraging strides. Boron agents have been used for both radiotherapy and chemotherapy.

Population Pharmacokinetic Analysis of Yimitasvir in Chinese Healthy Volunteers and Patients With Chronic Hepatitis C Virus Infection.

Yimitasvir is a novel, oral hepatitis C virus (HCV) non-structural protein 5A inhibitor for the treatment of chronic HCV genotype 1 infection. The objective of this analysis was to develop a population pharmacokinetic model of yimitasvir in Chinese healthy volunteers and HCV infection patients. The model was performed using data from 219 subjects across six studies.

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis.

Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection.

Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors.

We report herein the synthesis of novel ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors and the evaluation of pharmaceutical activity against five cancer cell lines (MDA-MB-231, BXPC-3, NCI-H1975, DU145 and 786O). Generally, the majority of compounds displayed strong anti-FAK enzymatic potencies (IC < 1 nM) and could effectively inhibit several class of cancer cell lines within the concentration of 3 μM in comparison with GSK2256098 as a reference. Among them, compound 4o is considered to be the most effective due to high sensitivity in antiproliferation.

Proanthocyanidins attenuate breast cancer-induced bone metastasis by inhibiting Irf-3/c-jun activation.

We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity.

Safety, Tolerability and Pharmacokinetics of Yimitasvir Phosphate Capsule, a Novel Oral Hepatitis C Virus NS5A Inhibitor, in Healthy Chinese Volunteers.

Background And Objectives: Yimitasvir is a novel oral hepatitis C virus non-structural protein 5A (NS5A) inhibitor. The aims of this first-in-human study were to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of yimitasvir in healthy adult Chinese volunteers and to assess the effect of food on yimitasvir pharmacokinetics.

Methods: Randomized, double-blind, placebo-controlled, single-ascending-dose (30, 100, 200 and 400 mg) and multiple-ascending-dose (100 and 200 mg once daily for 7 days) studies were performed in 32 and 24 subjects, respectively, in male and female adults.

The Current Status and Perspectives of Delivery Strategy for Boronbased Drugs.

Boron-containing compounds are essential micronutrients for animals and plants despite their low-level natural occurrence. They can strengthen the cell walls of the plants and they play important role in supporting bone health. However, surprisingly, boron-containing compounds are seldom found in pharmaceutical drugs.

Development of bunch shape monitor for high-intensity beam on the China ADS proton LINAC Injector II.

The development, performance, and testing of the longitudinal bunch shape monitor, namely, the Fast Faraday Cup (FFC), are presented in this paper. The FFC is an invasive instrument controlled by a stepper motor, and its principle of operation is based on a strip line structure. The longitudinal bunch shape was determined by sampling a small part of the beam hitting the strip line through a 1-mm hole.

DNA demethylation in the PTEN gene promoter induced by 5-azacytidine activates PTEN expression in the MG-63 human osteosarcoma cell line.

This study used the MG-63 osteosarcoma cell line to investigate the demethylation of the phosphate and tension homolog (PTEN) gene promoter and the change in PTEN gene expression levels, which are caused by the methylation inhibitor 5-azacytidine (5-Zac), and the association between the two. Different concentrations of 5-Zac (0, 5 and 10 μmol/l) were added into the MG-63 cell culture medium and the cells were cultured for 72 h. The following techniques were performed on the cells: Western blot analysis to detect the PTEN protein; reverse transcription-polymerase chain reaction (PCR) to detect the mRNA transcription levels of the PTEN gene; flow cytometry to detect the cell apoptotic rate; and sodium bisulfate to deal with the DNA of each group.

Cationic recognition by tert-butylcalix[4]arene-functionalized nanoprobes.

A nanoparticle-based strategy has been demonstrated using structurally-tailored tert-butylcalixarenes immobilized on gold nanoparticles to tune the guest access to the calixarene cone cavity for cationic recognition. This strategy exploits the interparticle charge-induced aggregation upon selective capture of metal cations into the nanoparticle-immobilized tert-butylcalixarenes, which produces calorimetric changes for the detection. A possible pathway for the binding of M(n+) into the t-BCA structure and the interparticle interaction is proposed for the formation of an electric double layer inducing the interparticle association responsible for the red-shifted surface plasmon resonance band of the nanoparticles.

[Treatment of fractures of extremities with expandable intramedullary nails].

Objective: To investigate the method and clinical effect of the expandable intramedullary nails on fractures of extremities.

Methods: Nineteen cases of extremities long tubular bone fractures were treated with Fixion expandable intramedullary nails.

Results: Nineteen cases were followed up for 4-18 months,all cases healed without any complications.