Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG(4) to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.X111313sciescopu

Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

Autocrine and paracrine factors are produced by balding dermal papilla (DP) cells following dihydrotestosterone (DHT)-driven alterations and are believed to be key factors involved in male pattern baldness. Herein we report that the IL-6 is upregulated in balding DP cells compared with non-balding DP cells. IL-6 was upregulated 3hours after 10–100nM DHT treatment, and ELISA showed that IL-6 was secreted from balding DP cells in response to DHT. IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) were expressed in follicular keratinocytes, including matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and suppressed proliferation of matrix cells in cultured human hair follicles. Moreover, rhIL-6 injection into the hypodermis of mice during anagen caused premature onset of catagen. Taken together, our data strongly suggest that DHT-inducible IL-6 inhibits hair growth as a paracrine mediator from the DP

Palladium Catalysts for Dehydrogenation of Ammonia Borane with Preferential B−H Activation

Cationic Pd(II) complexes catalyzed the dehydrogenation of ammonia borane in the most efficient manner with the release of 2.0 equiv of H_2 in less than 60 s at 25 °C. Most of the hydrogen atoms were obtained from the boron atom of the ammonia borane. The first step of the dehydrogenation reaction was elaborated using density functional theory calculations

Controlling the Magnetic Anisotropy of the van der Waals Ferromagnet Fe3GeTe2 through Hole Doping.

Identifying material parameters affecting properties of ferromagnets is key to optimized materials that are better suited for spintronics. Magnetic anisotropy is of particular importance in van der Waals magnets, since it not only influences magnetic and spin transport properties, but also is essential to stabilizing magnetic order in the two-dimensional limit. Here, we report that hole doping effectively modulates the magnetic anisotropy of a van der Waals ferromagnet and explore the physical origin of this effect. Fe3-xGeTe2 nanoflakes show a significant suppression of the magnetic anisotropy with hole doping. Electronic structure measurements and calculations reveal that the chemical potential shift associated with hole doping is responsible for the reduced magnetic anisotropy by decreasing the energy gain from the spin-orbit induced band splitting. Our findings provide an understanding of the intricate connection between electronic structures and magnetic properties in two-dimensional magnets and propose a method to engineer magnetic properties through doping

Severe Episodic Memory Impairment in a Patient With Clinical Features Compatible With Corticobasal Degeneration

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by asymmetric parkinsonism associated with apraxia, cortical sensory loss, and alien-limb phenomenon. Neuropsychological testing in patients with CBD typically shows deficits in executive functions, praxis, language, and visuospatial functioning, but not in memory. We report a CBD patient with severely impaired memory function but relatively mild motor symptoms. Detailed neuropsychological assessment showed significant verbal and visual memory deficits accompanied by frontal executive dysfunctions. Our observations indicate that CBD can in rare cases present with severe episodic memory impairment associated with frontal executive dysfunctions in the early stage of illness

Transmission of Seasonal Outbreak of Childhood Enteroviral Aseptic Meningitis and Hand-foot-mouth Disease

This study was conducted to evaluate the modes of transmission of aseptic meningitis (AM) and hand-foot-mouth disease (HFMD) using a case-control and a case-crossover design. We recruited 205 childhood AM and 116 HFMD cases and 170 non-enteroviral disease controls from three general hospitals in Gyeongju, Pohang, and Seoul between May and August in both 2002 and 2003. For the case-crossover design, we established the hazard and non-hazard periods as week one and week four before admission, respectively. In the case-control design, drinking water that had not been boiled, not using a water purifier, changes in water quality, and contact with AM patients were significantly associated with the risk of AM (odds ratio [OR]=2.8, 2.9, 4.6, and 10.9, respectively), while drinking water that had not been boiled, having a non-water closet toilet, changes in water quality, and contact with HFMD patients were associated with risk of HFMD (OR=3.3, 2.8, 6.9, and 5.0, respectively). In the case-crossover design, many life-style variables such as contact with AM or HFMD patients, visiting a hospital, changes in water quality, presence of a skin wound, eating out, and going shopping were significantly associated with the risk of AM (OR=18.0, 7.0, 8.0, 2.2, 22.3, and 3.0, respectively) and HFMD (OR=9.0, 37.0, 11.0, 12.0, 37.0, and 5.0, respectively). Our findings suggest that person-to-person contact and contaminated water could be the principal modes of transmission of AM and HFMD

Stable and High-Power Calcium-Ion Batteries Enabled by Calcium Intercalation into Graphite

Calcium-ion batteries (CIBs) are considered to be promising next-generation energy storage systems because of the natural abundance of calcium and the multivalent calcium ions with low redox potential close to that of lithium. However, the practical realization of high-energy and high-power CIBs is elusive owing to the lack of suitable electrodes and the sluggish diffusion of calcium ions in most intercalation hosts. Herein, it is demonstrated that calcium-ion intercalation can be remarkably fast and reversible in natural graphite, constituting the first step toward the realization of high-power calcium electrodes. It is shown that a graphite electrode exhibits an exceptionally high rate capability up to 2 A g(-1), delivering approximate to 75% of the specific capacity at 50 mA g(-1) with full calcium intercalation in graphite corresponding to approximate to 97 mAh g(-1). Moreover, the capacity stably maintains over 200 cycles without notable cycle degradation. It is found that the calcium ions are intercalated into graphite galleries with a staging process. The intercalation mechanisms of the "calciated" graphite are elucidated using a suite of techniques including synchrotron in situ X-ray diffraction, nuclear magnetic resonance, and first-principles calculations. The versatile intercalation chemistry of graphite observed here is expected to spur the development of high-power CIBs.