A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.     

Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

Biodegradation of poly(lactic acid)—cassava bagasse composites produced by injection molding

Neat poly (lactic acid) (PLA) and PLA/cassava bagasse (CB) composites were used to produce seedling tubes by extrusion and injection molding. The tubes were buried in simulated soil, and their biodegradation was investigated by weight loss, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). After 180 days, the composites' biodegradation was higher than neat PLA material, and the higher the CB content, the higher the biodegradation, which caused fissures and voids in the material. The biodegradation of PLA/CB composites increased the phosphorus content in the soil after 180 days. Composites of PLA with CB, an abundant agro-industrial residue in Brazil, are promising because they can reduce the environmental impact due to CB's proper destination, and the composites' costs and biodegradation are faster than pure PLA material. Both the faster biodegradation of the tube and the higher P content are advantageous for seedling tubes.     

Suitable fixation condition for rat liver using microwave irradiation and its application to the immunohistochemistry of glutamate dehydrogenase

In 50 patients auditory threshold and brain stem evoked potential studies were carried out before and after myelography. Due to the analysis of amplitudes and latencies of auditory brain stem measurements, significant functional disorders of the hearing organ and the auditory pathway could be demonstrated. In most of the patients these functional disorders were found to be subclinical, whereas 12 patients showed alterations extending from a subjectively slight hearing loss to an audiometrically objectified acute hearing loss depending on its intensity in each case. The reasons of these functional disorders could not be clarified. An open cochlear aqueduct through which perilymph enters the subarachnoidal space leading to a secondary endolymphatic hydrops can be considered as the cause in cases where manifest symptoms develop. The changes in brain stem audiometry can be additionally explained by changes in osmolality of the inner ear fluids which may lead to the development of an endolymphatic hydrops.     

Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity

The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.     

Computer simulation of morphological changes of grain boundary precipitates growing by the ledge mechanism

A previously developed computer model was modified to simulate the growth of grain boundary precipitates which grow by the ledge mechanism. The ledges were assumed to be nucleated in the grain boundary region at constant, parabolically decreasing, and random rates and to grow under the control of volume diffusion of solute to or from the riser of ledges. At lower under coolings at which the motion of individual ledges is slow, late-nucleated ledges soon catch up with first-nucleated ones, and precipitates tend to extend along the grain boundary: the overall precipitate shape is essentially that of a grain boundary allotriomorph. At larger undercoolings, first-nucleated ledges move fast to form a protuberance similar to Widmanstätten sideplates, while late-nucleated ones stay near the grain boundary region. The transition of precipitate shape from one to the other occurs in a very narrow range of supersaturation. The results are compared with various characteristics of the growth of proeutectoid ferrite allotriomorphs and sideplates in Fe-C alloys documented in the literature.     

Photocatalytic Property and Electronic Structure of Lanthanide-based Oxysulfides

Lanthanide-based oxysulfides and sulfide, LnTaO_3.5S_0.5, Ln₁₀OS₁₄ (Ln = La, Pr, Nd, Sm) and La₄In₅S₁₃, were successively synthesized by sulfurization in a flowing H₂S. The sulfurization decreased the band-gap energies from >4 eV to <3eV, because of the formation of occupied S3p orbitals on the top of valence band. In accordance with the small band gap, the H₂ evolution from a 0.01 M Na₂S and 0.01 M Na₂SO₃ solution system was observed under irradiation of light up to >500 nm. The rate of H₂ evolution under light irradiation of >500 nm increased in the order of Ni/LaTaO_3.5S_0.5 < Ru/La₁₀OS₁₄ < Pt/La₄In₅S₁₃.     

Local droplet diameter variation in a stirred tank

The local variation of droplet diameter in a stirred tank was measured in the vicinity of the impeller and at another region. The degree of difference in droplet diameter between regions increases with the impeller speed. A correlation equation between the local difference in droplet diameter and the frequencies of coalescence and circulation of the droplet was derived according to the circulation interaction model. The degree of local difference in droplet diameter was found to be controlled strongly by the ratio of coalescence to circulation frequency.