A Mode-Coupling Model of Colloid Thermophoresis in Aqueous Systems: Temperature and Size Dependencies of the Soret Coefficient.

Thermophoresis allows for the manipulation of colloids in systems containing a temperature gradient. A deep understanding of the phenomena at the molecular level allows for increased control and manipulation strategies. We developed a microscopic model revealing different coupling mechanisms for colloid thermophoresis under local thermodynamic equilibrium conditions. The model has been verified through comparison with a variety of previously published experimental data and shows good agreement across significantly different systems. We found five different temperature-dependent contributions to the Soret coefficient, two from bulk properties and three from interfacial interactions between the fluid medium and the colloid. Our analysis shows that the Soret coefficient for nanosized particles is governed by the competition between the electrostatic and hydration interfacial interactions, while bulk contributions become more pronounced for protein systems. This theory can be used as a guide to design thermophoretic transport, which is relevant for sensing, focusing, and separation at the microscale.

Colloid thermophoresis in the dilute electrolyte concentration regime: from theory to experiment.

Colloid thermophoresis in aqueous media is vital for numerous applications in nanoscience and life sciences. To date, a general description of colloid thermophoresis in DI water has not been determined. Here, we describe a theoretical model within the framework of the Fokker-Planck formalism and the flickering cluster concept to describe the hydration entropy effect on the thermophoretic behaviour of colloids suspended in DI water and compare this to new experimental results. We built an experimental platform to allow for rapid and robust temperature control and investigate the thermophoretic behaviour of silica microspheres with different sizes at various background temperatures for comparison. In this work, the ionic shielding effect is accounted for by using the well-known Duhr-Dhont's model, and the hydration layer effect is determined using the developed theoretical model. For the latter, our model reveals that the sign of the Soret coefficient is governed by the interplay between the binding energy and the chemical potential of water molecules, which were found to be in the same order of magnitude. We show that our analysis accurately describes the experimental behaviour of colloidal particles that opens a new avenue for developing versatile trapping and separation techniques for various colloidal particles in aqueous systems according to their size and background temperature.

Pharmacokinetics and Safety of Intravenous and Subcutaneous Auto-injector Single-dose Belimumab in Healthy Chinese Volunteers: A phase 1, Randomized, Open-label Study.

INTRODUCTION: Belimumab is a recombinant human immunoglobulin G1λ monoclonal antibody indicated as an intravenous (IV) 10 mg/kg and subcutaneous (SC) 200-mg dose for the treatment of systemic lupus erythematosus (SLE). Belimumab 10 mg/kg IV has been approved for the treatment of patients with SLE in China. This phase 1 study investigated the pharmacokinetics (PK), safety, and tolerability of belimumab 200 mg SC and the approved IV formulation in a healthy Chinese population. METHODS: This was a 13-week open-label, randomized, parallel-group study in healthy Chinese volunteers. Eligible volunteers were randomized (1:2) to receive a single dose of IV or SC (via auto-injector) belimumab 200 mg. PK and safety endpoints were evaluated using descriptive statistics. RESULTS: Thirty-six healthy Chinese volunteers were enrolled and all completed the study. Concentration-time profiles were as expected for both formulations. Overall, 130 adverse events (AEs) were reported, with 28 AEs reported in 11 (91.7%) volunteers in the IV group and 102 AEs in 24 (100%) volunteers in the SC group. Of the 130 AEs, 104 (80.0%) were considered to be treatment-related (27 [20.8% of total AEs] treatment-related AEs in the IV group; 77 [59.2% of total AEs] in the SC group). Although the occurrence of AEs was higher in the SC group, most volunteers (91.7%) experienced AEs of mild intensity. The most frequently reported AEs included injection site pain (n = 19 [79.2%]) and oropharyngeal pain (n = 5 [20.8%]) in the SC group, and positive bacterial test, upper respiratory tract infection, blood uric acid increase, white blood cell count increase, asthenia, and diarrhea (n = 2 [16.7%], each) in the IV group. CONCLUSIONS: PK profiles of 200 mg SC and IV belimumab administrations were similar to previous studies, and safety profiles were acceptable, supporting the use of the SC dose in Chinese patients with SLE. TRIAL REGISTRATION: NCT04136145.

Systemic lupus erythematosus (SLE) is a long-term autoimmune disease that affects patients' quality of life. Belimumab is an antibody used in several countries in combination with standard therapy to treat patients with SLE. Belimumab can be given monthly either via a vein (intravenous, IV) or weekly under the skin (subcutaneous, SC). In China, only the IV belimumab has been approved for the treatment of patients with SLE. Therefore, we carried out a study in healthy Chinese volunteers to compare the concentration of a single dose of IV or SC belimumab in the body over time, and to investigate the safety of SC belimumab to assist its approval in China. In our study, the concentration and safety of both administration methods were similar; however, more volunteers from the SC treatment group had urinalysis-related side effects compared with the IV treatment group. All of these side effects were of mild intensity and did not require treatment. These results suggest that SC belimumab could be used for the treatment of Chinese patients with SLE.

Age-dependent down-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 4 causes deterioration of canine sinoatrial node function.

The activity of pacemaker cells in the sinoatrial node (SAN) is an indicator of normal sinus rhythm. Clinical studies have revealed that the dysfunction of the SAN progressively increases with aging. In this study, we determined the changes in hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) expression and the relationship between aging and canine SAN dysfunction. The results of cardiac electrophysiological determination revealed that the intrinsic heart rate decreased from 168 ± 11 beats min-1 in young canines to 120 ± 9 beats min-1 in adults and to 88 ± 9 beats min-1 in aged canines. The sinus node recovery time (SNRT) increased from 412 ± 32 ms in young canines to 620 ± 56 ms in adults and to 838 ± 120 ms in aged canines. Corrected SNRT (CSNRT) increased from 55 ± 12 ms in young canines to 117 ± 27 ms in adults and to 171 ± 37 ms in aged canines. These results indicated that SAN function deteriorated with aging in the canine heart. However, histological staining illustrated that fibrosis was not significantly increased with aging in canine SAN. Real-time polymerase chain reaction indicated that the expression of HCN4 mRNA was downregulated in the elderly canine SAN. Similarly, we also verified that HCN4 protein expression within the SAN declined with aging via immunofluorescence staining and western blot analysis. Taken together, our data show that electrical remodeling, related to the down-regulation of HCN4, is responsible for the gradually increased incidence of SAN dysfunction with aging. Our results provide further evidence for explaining the mechanisms of age-related deterioration in the SAN.

Snail1 is involved in de novo cardiac fibrosis after myocardial infarction in mice.

Epithelial-mesenchymal transition (EMT) is an important mechanism of cardiac fibrosis after myocardial infarction (MI). However, it remains unclear whether Snail1, an important regulator of EMT, is involved in cardiac fibrosis. In this study, we explored the expression patterns of Snail1 and a cardiac fibrosis marker-periostin-after MI in mice and then investigated the co-expression between Snail1 and periostin after MI in mice. Our results showed that the mRNA and protein levels of Snail1 and periostin were significantly increased in the infarct area. The Snail1 expression pattern appeared to be parabolic within 14 days after MI. In addition, after MI, all Snail1-positive cells were able to express periostin. These results indicate that Snail1 is mainly activated in the infarct area and is involved in de novo cardiac fibrosis after MI in mice. Thus, it is a potential molecular target in the development of drug interventions for ventricular remodeling after MI.