Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Counting d-Orbital Vacancies of Transition-Metal Catalysts for the Sulfur Reduction Reaction.

The electrocatalytic sulfur reduction reaction (SRR) would allow the production of renewable high-capacity rechargeable lithium-sulfur (Li-S) batteries using sustainable and nontoxic elemental sulfur as a cathode material, but its slow reaction rate causes a serious shuttle effect and dramatically reduces the capacity. We found that a catalyst composed of Pd nanoparticles supported by ordered mesoporous carbon (Pd/OMC) had a high reaction rate in the SRR, and a Li-S battery assembled with this catalyst had a low shuttle constant of 0.031 h-1 and a high-rate performance with a specific capacity of 1527 mAh g-1 at 0.1 C which is close to the theoretical value. The high activity of Pd/OMC with a d-orbital vacancy of 0.87 e was predicted from a volcano relationship between the d charge for the metal and the adsorption activation entropy and reaction rate for the SRR by examining Pd, Au, Pt, Rh, and Ru transition-metal nanocatalysts. The strategy of using a single electronic structure descriptor to design high-efficiency SRR catalysts has suggested a way to produce practical Li-S batteries.

Chitosan-based hollow nanofiber membranes with polyvinylpyrrolidone and polyvinyl alcohol for efficient removal and filtration of organic dyes and heavy metals.

Due to their large specific surface area and numerous diffusion channels, hollow fibers are widely used in wastewater treatment. In this study, we successfully synthesized a chitosan (CS)/polyvinylpyrrolidone (PVP)/polyvinyl alcohol (PVA) hollow nanofiber membrane (CS/PVP/PVA-HNM) via coaxial electrospinning. This membrane demonstrated remarkable permeability and adsorption separation. Specifically, the CS/PVP/PVA-HNM had a pure water permeability of 4367.02 L·m-2·h-1·bar-1. The hollow electrospun nanofibrous membrane exhibited a continuous interlaced nanofibrous framework structure with the extraordinary advantages of high porosity and high permeability. The rejection ratios of CS/PVP/PVA-HNM for Cu2+, Ni2+, Cd2+, Pb2+, malachite green (MG), methylene blue (MB) and crystal violet (CV) were 96.91 %, 95.29 %, 87.50 %, 85.13 %, 88.21 %, 83.91 % and 71.99 %, and the maximum adsorption capacities were 106.72, 97.46, 88.10, 87.81, 53.45, 41.43, and 30.97 mg·g-1, respectively. This work demonstrates a strategy for the synthesis of hollow nanofibers, which provides a novel concept for the design and fabrication of highly efficient adsorption and separation membranes.

Recent advances and perspectives of CeO2-based catalysts: Electronic properties and applications for energy storage and conversion.

Cerium dioxide (CeO2, ceria) has long been regarded as one of the key materials in modern catalysis, both as a support and as a catalyst itself. Apart from its well-established use (three-way catalysts and diesel engines), CeO2 has been widely used as a cocatalyst/catalyst in energy conversion and storage applications. The importance stems from the oxygen storage capacity of ceria, which allows it to release oxygen under reducing conditions and to store oxygen by filling oxygen vacancies under oxidizing conditions. However, the nature of the Ce active site remains not well understood because the degree of participation of f electrons in catalytic reactions is not clear in the case of the heavy dependence of catalysis theory on localized d orbitals at the Fermi energy E F . This review focuses on the catalytic applications in energy conversion and storage of CeO2-based nanostructures and discusses the mechanisms for several typical catalytic reactions from the perspectives of electronic properties of CeO2-based nanostructures. Defect engineering is also summarized to better understand the relationship between catalytic performance and electronic properties. Finally, the challenges and prospects of designing high efficiency CeO2-based catalysts in energy storage and conversion have been emphasized.

Chitosan/polyvinylpyrrolidone/polyvinyl alcohol/carbon nanotubes dual layers nanofibrous membrane constructed by electrospinning-electrospray for water purification.

Nanofibrous membrane have great potential in the field of water purification due to the high porosity and large specific surface area. Herein, a dual layers nanofibrous membrane was prepared by combining an active layer containing carbon nanotubes (CNTs) with a porous chitosan (CS)/polyvinylpyrrolidone (PVP)/polyvinyl alcohol (PVA) nanofibrous support layer via electrospinning-electrospray technique for highly efficient heavy metal and organic pollutants removal. Incorporating CNTs into the active layer offered additional nanochannels which significantly enhanced pure water permeate flux (1533.26 L·m-2·h-1) and heavy metal ions/dyes rejection (Cu2+ 95.68 %, Ni2+ 93.86 %, Cd2+ 88.52 %, Pb2+ 80.41 %, malachite green 87.20 %, methylene blue 76.33 %, and crystal violet 63.39 %). The optimal membranes were formed with a thickness of 20 µm and a roughness of 142 nm while still showing good perm-selectivity compared with commercial PVDF membrane. Moreover, the constructed membrane exhibited good antifouling property and long-term stability during filtration process. This work provides a new strategy to fabricate advanced separation membranes for water treatment.

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective: We investigated the relationships between interleukin- (IL-) 1ß and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods: The genotype and allele frequency distribution of IL-1ß and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1ß and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results: Significant differences were detected in the distribution of IL-1ß (-511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489-5.416). The IL-1ß (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1ß level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1ß level was significantly different between IL-1ß (-511C/T) locus variants (P < 0.05). Conclusion: The IL-1ß (-511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

Preparation and performance evaluation of chitosan/polyvinylpyrrolidone/polyvinyl alcohol electrospun nanofiber membrane for heavy metal ions and organic pollutants removal.

In this work, a novel electrospun chitosan (CS)/polyvinylpyrrolidone (PVP)/polyvinyl alcohol (PVA) nanofibrous membrane was prepared to remove heavy metal ions and organic pollutants from water. The nanofiber morphologies were adjusted through the optimal electrospinning process parameters. Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) characterizations indicated that a well-crosslinked CS/PVP/PVA nanofiber film was formed. Under the optimize conditions, the obtained CS/PVP/PVA nanofiber membranes exhibited porous and uniform nanofibrous structures with an average diameter of 160 nm and a pure water permeability of 4518.91 L·m-2·h-1·bar-1. In addition, the adsorption and separation performance of CS/PVP/PVA nanofiber membranes were evaluated with Cu(II), Ni(II), Cd(II), Pb(II) and Methylene Blue (MB), Malachite Green (MG) as target ions and dyes. The results showed that the retention rate of CS/PVP/PVA nanofiber membranes for Cu(II), Ni(II), Cd(II), Pb(II), MG and MB can reach 94.20%, 90.35%, 83.33%, 80.12%, 84.01% and 69.91%, respectively. The adsorption capacities of Cu(II), Ni(II), Cd(II), Pb(II), MG and MB were 34.79, 25.24, 18.07, 16.05, 17.86 and 13.27 mg g-1. The adsorption kinetics of heavy metal ions and dyes by the nanofiber membranes can be explained by the Langmuir isotherm model and represented by the pseudo-second-order kinetic mechanism that determined the spontaneous chemisorption process. This study provides a synthetic approach to membranes for the removal of organic and heavy metal micropollutants from water.

Biocompatible near-infrared fluorescent nanoparticles for macro and microscopic in vivo functional bioimaging.

Near-infrared (NIR) imaging technology has been widely used for biomedical research and applications, since it can achieve deep penetration in biological tissues due to less absorption and scattering of NIR light. In our research, polymer nanoparticles with NIR fluorophores doped were synthesized. The morphology, absorption/emission features and chemical stability of the fluorescent nanoparticles were characterized, separately. NIR fluorescent nanoparticles were then utilized as bright optical probes for macro in vivo imaging of mice, including sentinel lymph node (SLN) mapping, as well as distribution and excretion monitoring of nanoparticles in animal body. Furthermore, we applied the NIR fluorescent nanoparticles in in vivo microscopic bioimaging via a confocal microscope. Under the 635 nm-CW excitation, the blood vessel architecture in the ear and the brain of mice, which were administered with nanoparticles, was visualized very clearly. The imaging depth of our one-photon microscopy, which was assisted with NIR fluorescent nanoprobes, can reach as deep as 500 µm. Our experiments show that NIR fluorescent nanoparticles have great potentials in various deep-tissue imaging applications.