Comparative pharmacokinetics of free doxorubicin and a liposomal formulation in cats following intravenous administration

Doxorubicin, a potent chemotherapeutic agent used extensively in cancer treatment, displays complex pharmacokinetic behavior, especially across various formulations. With a rising incidence of cancer cases in cats, understanding the drug’s pharmacokinetics in feline subjects remains a critical yet unexplored area. Hence, this study investigated the pharmacokinetic profile of doxorubicin after slow intravenous administration of doxorubicin hydrochloride (DOX·HCl) or doxorubicin hydrochloride pegylated liposome (DOX·HCl-PLI) in twelve cats at a single dose of 20 mg/m2. Blood samples collected at pretreatment time (0 h) and over 192 h were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The obtained pharmacokinetic parameters of doxorubicin revealed significant differences between the two formulations and were as follows: elimination half-life (T1/2λz) of 5.00 ± 3.20 h (DOX·HCl) and 17.62 ± 8.13 h (DOX·HCl-PLI), area under the concentration/time curve from 0 to last point (AUClast) of 0.67 ± 0.12 μg hr./mL (DOX·HCl) and 783.09 ± 267.29 μg hr./mL (DOX·HCl-PLI), and total body clearance (CL_obs) of 27098.58 ± 5205.19 mL/h/m2 (DOX·HCl) and 28.65 ± 11.09 mL/h/m2 (DOX·HCl-PLI). Additionally, differences were also detected in the apparent volume of distribution (Vz_obs) with 178.56 ± 71.89 L/m2 (DOX·HCl) and 0.64 ± 0.20 L/m2 (DOX·HCl-PLI), and the maximum plasma concentration (Cmax) with 2.25 ± 0.30 μg/mL (DOX·HCl) and 24.02 ± 5.45 μg/mL (DOX·HCl-PLI). Notably, low concentration of doxorubicinol, the metabolite of doxorubicin, was detected in plasma after administration of DOX·HCl, with even less present when DOX·HCl-PLI was administered. This investigation provides valuable insights into the distinct pharmacokinetic behaviors of DOX·HCl and DOX·HCl-PLI in cats, contributing essential groundwork for future studies and potential clinical applications in feline oncology

Emergent superconducting fluctuations in a compressed kagome superconductor

The recent discovery of superconductivity (SC) and charge density wave (CDW) in kagome metals AV3Sb5 (A = K, Rb, Cs) provides an ideal playground for the study of emergent electronic orders. Application of moderate pressure leads to a two-dome-shaped SC phase regime in CsV3Sb5 accompanied by the destabilizing of CDW phase; such unconventional evolution of SC may involve the pressure-induced formation of a new stripe-like CDW order resembling that in La-214 cuprate superconductors. Nonetheless, the nature of this pressure-tuned SC state and its interplay with the stripe order are yet to be explored. Here, we perform soft point-contact spectroscopy (SPCS) measurements in CsV3Sb5 to investigate the evolution of superconducting order parameter with pressure. Surprisingly, we find that the superconducting gap is significantly enhanced between the two SC domes, at which the zero-resistance temperature is suppressed and the transition is remarkably broadened. Moreover, the temperature dependence of the SC gap in this pressure range severely deviates from the conventional BCS behavior, evidencing for strong Cooper pair phase fluctuations. These findings reveal the complex intertwining of the stripe-like CDW with SC in the compressed CsV3Sb5, suggesting striking parallel to the cuprate superconductor La2-xBaxCuO4. Our results point to the essential role of charge degree of freedom in the development of intertwining electronic orders, thus provides new constraints for theories.Comment: 16 pages, 4 figure

Selection of Anti-Sulfadimidine Specific ScFvs from a Hybridoma Cell by Eukaryotic Ribosome Display

BACKGROUND:Ribosome display technology has provided an alternative platform technology for the development of novel low-cost antibody based on evaluating antibiotics derived residues in food matrixes. METHODOLOGY/PRINCIPAL FINDINGS:In our current studies, the single chain variable fragments (scFvs) were selected from hybridoma cell lines against sulfadimidine (SM(2)) by using a ribosome library technology. A DNA library of scFv antibody fragments was constructed for ribosome display, and then mRNA-ribosome-antibody (MRA) complexes were produced by a rabbit reticulocyte lysate system. The synthetic sulfadimidine-ovalbumin (SM(2)-OVA) was used as an antigen to pan MRA complexes and putative scFv-encoding genes were recovered by RT-PCR in situ following each panning. After four rounds of ribosome display, the expression vector pCANTAB5E containing the selected specific scFv DNA was constructed and transformed into Escherichia coli HB2151. Three positive clones (SAS14, SAS68 and SAS71) were screened from 100 clones and had higher antibody activity and specificity to SM(2) by indirect ELISA. The three specific soluble scFvs were identified to be the same molecular weight (approximately 30 kDa) by Western-blotting analysis using anti-E tag antibodies, but they had different amino acids sequence by sequence analysis. CONCLUSIONS/SIGNIFICANCE:The selection of anti-SM(2) specific scFv by in vitro ribosome display technology will have an important significance for the development of novel immunodetection strategies for residual veterinary drugs

High-intensity exercise to promote accelerated improvements in cardiorespiratory fitness (HI-PACE): study protocol for a randomized controlled trial

Background: African Americans have a disproportionate prevalence and incidence of type 2 diabetes compared with Caucasians. Recent evidence indicates that low cardiorespiratory fitness (CRF) level, an independent risk factor for type 2 diabetes, is also more prevalent in African Americans than Caucasians. Numerous studies in Caucasian populations suggest that vigorous exercise intensity may promote greater improvements in CRF and other type 2 diabetes risk factors (e.g., reduction of glucose/insulin levels, pulse wave velocity, and body fat) than moderate intensity. However, current evidence comparing health benefits of different aerobic exercise intensities on type 2 diabetes risk factors in African Americans is negligible. This is clinically important as African Americans have a greater risk for type 2 diabetes and are less likely to meet public health recommendations for physical activity than Caucasians. The purpose of the HI-PACE (High-Intensity exercise to Promote Accelerated improvements in CardiorEspiratory fitness) study is to evaluate whether high-intensity aerobic exercise elicits greater improvements in CRF, insulin action, and arterial stiffness than moderate-intensity exercise in African Americans. Methods/Design: A randomized controlled trial will be performed on overweight and obese (body mass index of 25–45 kg/m2) African Americans (35–65 years) (n = 60). Participants will be randomly assigned to moderate-intensity (MOD-INT) or high-intensity (HIGH-INT) aerobic exercise training or a non-exercise control group (CON) for 24 weeks. Supervised exercise will be performed at a heart rate associated with 45–55% and 70–80% of VO2 max in the MOD-INT and HIGH-INT groups, respectively, for an exercise dose of 600 metabolic equivalents of task (MET)-minutes per week (consistent with public health recommendations). The primary outcome is change in CRF. Secondary outcomes include change in insulin sensitivity (measured via an intravenous glucose tolerance test), skeletal muscle mitochondrial oxidative capacity (via near-infrared spectroscopy), skeletal muscle measurements (i.e., citrate synthase, COX IV, GLUT-4, CPT-1, and PGC1-α), arterial stiffness (via carotid-femoral pulse wave velocity), body fat, C-reactive protein, and psychological outcomes (quality of life/exercise enjoyment). Discussion: The anticipated results of the HI-PACE study will provide vital information on the health effects of high-intensity exercise in African Americans. This study will advance health disparity research and has the potential to influence future public health guidelines for physical activity

3D Microstructure Inhibits Mesenchymal Stem Cells Homing to the Site of Liver Cancer Cells on a Microchip

The cell microenvironment consists of multiple types of biophysical and biochemical factors, and represents a complex integrated system that is variable in both time and space. Studies show that changes in biochemical and biophysical factors in cell microenvironments result in significant changes in cellular forms and functions, especially for stem cells. Mesenchymal stem cells (MSCs) are derived from adult stem cells of the mesoderm and play an important role in tissue engineering, regenerative medicine and even cancer therapy. Furthermore, it is found that MSCs can interact with multiple types of tumor cells. The interaction is reflected as two totally different aspects. The negative aspect is that MSCs manifest as tumor-associated fibroblasts and could induce migration of cancer cells and promote tumor formation. On the other hand, MSCs can home to sites of the tumor microenvironment, directionally migrate toward tumor cells and cause tumor cell apoptosis. In this study, we designed and made a simple microfluidic chip for cell co-culture, and studied stem cell homing behavior in the interaction between MSCs and liver cancer cells. Moreover, by etching a three-dimensional microstructure on the base and adding transforming growth factor-β (TGF-β) in the co-culture environment, we studied the impact of biophysical and biochemical factors on stem cell homing behavior, and the causes of such impact

Using Long-Term Earth Observation Data to Reveal the Factors Contributing to the Early 2020 Desert Locust Upsurge and the Resulting Vegetation Loss

Massive desert locust swarms have been threatening and devouring natural vegetation and agricultural crops in East Africa and West Asia since 2019, and the event developed into a rare and globally concerning locust upsurge in early 2020. The breeding, maturation, concentration and migration of locusts rely on appropriate environmental factors, mainly precipitation, temperature, vegetation coverage and land-surface soil moisture. Remotely sensed images and long-term meteorological observations across the desert locust invasion area were analyzed to explore the complex drivers, vegetation losses and growing trends during the locust upsurge in this study. The results revealed that (1) the intense precipitation events in the Arabian Peninsula during 2018 provided suitable soil moisture and lush vegetation, thus promoting locust breeding, multiplication and gregarization; (2) the regions affected by the heavy rainfall in 2019 shifted from the Arabian Peninsula to West Asia and Northeast Africa, thus driving the vast locust swarms migrating into those regions and causing enormous vegetation loss; (3) the soil moisture and NDVI anomalies corresponded well with the locust swarm movements; and (4) there was a low chance the eastwardly migrating locust swarms would fly into the Indochina Peninsula and Southwest China

Inhibition of Phenol from Entering into Condensed Freshwater by Activated Persulfate during Solar-Driven Seawater Desalination

Recently, solar-driven seawater desalination has received extensive attention since it can obtain considerable freshwater by accelerating water evaporation at the air–water interface through solar evaporators. However, the high air–water interface temperature can cause volatile organic compounds (VOCs) to enter condensed freshwater and result in water quality safety risk. In this work, an antioxidative solar evaporator, which was composed of MoS2 as the photothermal material, expandable polyethylene (EPE) foam as the insulation material, polytetrafluoroethylene (PTFE) plate as the corrosion resistant material, and fiberglass membrane (FB) as the seawater delivery material, was fabricated for the first time. The activated persulfate (PS) methods, including peroxymonosulfate (PMS) and peroxodisulfate (PDS), were applied to inhibit phenol from entering condensed freshwater during desalination. The distillation concentration ratio of phenol (RD) was reduced from 76.5% to 0% with the addition of sufficient PMS or PDS, which means that there was no phenol in condensed freshwater. It was found that the Cl− is the main factor in activating PMS, while for PDS, light, and heat are the dominant. Compared with PDS, PMS can make full utilization of the light, heat, Cl− at the evaporator’s surface, resulting in more effective inhibition of the phenol from entering condensed freshwater. Finally, though phenol was efficiently removed by the addition of PMS or PDS, the problem of the formation of the halogenated distillation by-products in condensed freshwater should be given more attention in the future