Mechanisms of Non-Fresh Groundwater Presence at Water Tables in Highly Permeable Coastal Aquifers.

Coastal aquifers with high hydraulic conductivities on the order of 10-2 m s-1 have unconventional salinity distributions with the presence of non-fresh groundwater at the water table over a wide swath near the coast. This study aims to unravel the mechanisms underlying the phenomenon via numerical simulations for variably saturated, density-driven flow and solute transport in porous media. The simulation results indicate that the existence of non-fresh groundwater at the water table is attributed to the upward mass flux in the saturated zone near the coast, which transports solute from deeper groundwater toward the water table. With high hydraulic conductivity, the upward mass flux becomes prominent at shallower elevations because of the high Darcy flux and the shallow saline groundwater. The upward mass flux has two main drivers, upward advection by the upward flow component and transverse dispersion by the seaward flow component. The advective mass flux dominates over the transverse dispersion in the deep part of the saturated zone where only groundwater with sea water salinity exists. In contrast, the transverse dispersion becomes more pronounced than the upward advection in the shallow saturated zone just beneath the water table and in the unsaturated zone immediately above the water table. Our findings help interpret the unconventional salinity distributions observed and elucidate the unique dynamics of groundwater flow and solute transport in highly permeable coastal aquifers.

Association Between Workplace Social Support and Use of Health-Promoting Wearable Devices: A Prospective Cohort Study of Japanese Employees.

We examined the relationship between workplace environmental factors, including support from supervisors and colleagues, and the continued use of a wearable device meant to promote occupational health. One hundred employees at a Japanese manufacturing company participated in a 3-month study, and information related to their physical health status was recorded by a wearable device. We analyzed the results using the χ2 test and logistic regression analysis. We found that men aged 40-49 years and employees reporting low support from supervisors and colleagues were significantly more likely to be continuing device users. Participants with low workplace support had adjusted odds ratios approximately two to three times higher than those with high levels of support, which was significant. Employees with low workplace support were able to communicate at work, access appropriate support, and enthusiastically participate in occupational health promotion with little psychological difficulty in using the device. Occupational health promotion using wearable devices can complement traditional face-to-face occupational health promotion.

Cesium-137 stored on and discharged from banks of an agricultural canal in Iitate, Fukushima.

This study aimed to investigate the dynamics of 137Cs around banks along an agricultural canal for paddy fields in Iitate, Fukushima, Japan. Five plots (2.4-12.6 m2) on the banks were monitored intermittently during six time periods from May 2018 to November 2019. We directly collected runoff water samples discharged from the banks followed by partitioning it into particulate and dissolved fractions and determining 137Cs in them. To investigate the source of 137Cs in the runoff water, we sequentially extracted 137Cs in various chemical forms from litter samples collected on the banks. The results showed that the discharge rates of the dissolved 137Cs per unit area from the plots were lower than those observed at the downstream of the agricultural canal, whereas more than 50% of the 137Cs discharged from the plots was in the dissolved fraction. Moreover, the results indicate that 137Cs stored in the standing plants and the litter was the primary source of the dissolved 137Cs discharged into the agricultural canal. The concentrations of the water-soluble 137Cs in the litter per plot area may have been retained by the sufficiently higher concentrations of 137Cs in litter in other chemical forms and those in the standing plants, which are the source of the litter.

Two-dimensional ground-state mapping of a Mott-Hubbard system in a flexible field-effect device.

A Mott insulator sometimes induces unconventional superconductivity in its neighbors when doped and/or pressurized. Because the phase diagram should be strongly related to the microscopic mechanism of the superconductivity, it is important to obtain the global phase diagram surrounding the Mott insulating state. However, the parameter available for controlling the ground state of most Mott insulating materials is one-dimensional owing to technical limitations. Here, we present a two-dimensional ground-state mapping for a Mott insulator using an organic field-effect device by simultaneously tuning the bandwidth and bandfilling. The observed phase diagram showed many unexpected features such as an abrupt first-order superconducting transition under electron doping, a recurrent insulating phase in the heavily electron-doped region, and a nearly constant superconducting transition temperature in a wide parameter range. These results are expected to contribute toward elucidating one of the standard solutions for the Mott-Hubbard model.

Bone Regeneration with a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma.

Mesenchymal stem cells (MSCs) have the potential to directly differentiate into osteogenic cells and efficiently regenerate bone tissue. Adipose-derived stem cells (ASCs) have the potential to differentiate into an osteogenic lineage, too. In addition, ASCs can be readily harvested in large numbers with low donor-site morbidity. Meanwhile, recent reports have demonstrated that platelet-rich plasma (PRP) contains a variety of growth factors and may be a powerful biological autologous cocktail of growth factors for tissue engineering.We have shown that ASC/PRP admixture had dramatic effects on bone regeneration in a rat calvarial defect model, not only through the osteogenic potential of ASCs, but also through the release of cytokines by platelets in PRP, which, in turn, support ASCs.In this chapter, we introduce the bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model.

Current status of bone regeneration using adipose-derived stem cells.

Many bone regeneration therapies have been developed for clinical use and have variable outcomes and serious limitations. The goal of bone regeneration is to repair a bone defect in a stable and durable manner. Cellular strategies play an important role in bone tissue engineering. Clinical factors important for successful bone regeneration are the recruitment of cells to the defect site and the production of a suitable extracellular matrix consistent with bone tissues. Adipose-derived stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort. They are multipotent somatic stem cells and have a strong potential to differentiate and secrete growth factors. In this review, we discuss the osteogenic potential of ASCs with/without several types of scaffolds in vivo and their clinical application for bone regeneration.

A Low-Level Carbon Dioxide Laser Promotes Fibroblast Proliferation and Migration through Activation of Akt, ERK, and JNK.

BACKGROUND: Low-level laser therapy (LLLT) with various types of lasers promotes fibroblast proliferation and migration during the process of wound healing. Although LLLT with a carbon dioxide (CO2) laser was also reported to promote wound healing, the underlying mechanisms at the cellular level have not been previously described. Herein, we investigated the effect of LLLT with a CO2 laser on fibroblast proliferation and migration. MATERIALS AND METHODS: Cultured human dermal fibroblasts were prepared. MTS and cell migration assays were performed with fibroblasts after LLLT with a CO2 laser at various doses (0.1, 0.5, 1.0, 2.0, or 5.0 J/cm2) to observe the effects of LLLT with a CO2 laser on the proliferation and migration of fibroblasts. The non-irradiated group served as the control. Moreover, western blot analysis was performed using fibroblasts after LLLT with a CO2 laser to analyze changes in the activities of Akt, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK), which are signaling molecules associated with cell proliferation and migration. Finally, the MTS assay, a cell migration assay, and western blot analysis were performed using fibroblasts treated with inhibitors of Akt, ERK, or JNK before LLLT with a CO2 laser. RESULTS: In MTS and cell migration assays, fibroblast proliferation and migration were promoted after LLLT with a CO2 laser at 1.0 J/cm2. Western blot analysis revealed that Akt, ERK, and JNK activities were promoted in fibroblasts after LLLT with a CO2 laser at 1.0 J/cm2. Moreover, inhibition of Akt, ERK, or JNK significantly blocked fibroblast proliferation and migration. CONCLUSIONS: These findings suggested that LLLT with a CO2 laser would accelerate wound healing by promoting the proliferation and migration of fibroblasts. Activation of Akt, ERK, and JNK was essential for CO2 laser-induced proliferation and migration of fibroblasts.

Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.

BACKGROUND: Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons. RESULTS: The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group. CONCLUSION: The study findings demonstrate that the application of ASCs results in significant improvement in the pathological findings associated with tendinopathy and the normalization of collagen ratios within the affected tendon. CLINICAL RELEVANCE: Subcutaneous adipose tissue can be harvested easily, and ASC administration might have the potential to rapidly treat tendinopathy.

Coadministration of adipose-derived stem cells and control-released basic fibroblast growth factor facilitates angiogenesis in a murine ischemic hind limb model.

OBJECTIVE: Adipose-derived stem cells (ASCs) have angiogenic potential owing to their differentiation into endothelial cells and their release of angiogenic growth factors to elicit paracrine effects. In addition, control-released basic fibroblast growth factor (bFGF) sustained with a gelatin hydrogel also supports effective angiogenesis. We sought to determine if coadministration of ASCs and control-released bFGF into murine ischemic limbs facilitates angiogenesis. METHODS: Levels of growth factors in the conditioned media of ASCs cultured with or without control-released bFGF were measured by enzyme-linked immunosorbent assays. A murine ischemic hind limb model was generated and intramuscularly injected with the following: gelatin hydrogel (group 1), a high number of ASCs (group 2), control-released bFGF (group 3), a small number of ASCs and control-released bFGF (group 4), and a high number of ASCs and control-released bFGF (group 5). Macroscopic and microscopic vascular changes were evaluated until day 7 by laser Doppler perfusion imaging and histologic analyses, respectively. RESULTS: Secretion of hepatocyte growth factor, vascular endothelial growth factor, and transforming growth factor-ß1 was enhanced by control-released bFGF. Vascular improvement was achieved in groups 4 and 5 according to laser Doppler perfusion imaging. Hematoxylin and eosin staining and CD31 immunohistochemical staining demonstrated an increase in the vascular density, vessel diameter, and thickness of vessel walls in groups 4 and 5. Cells positively stained for CD146, α-smooth muscle actin, and transforming growth factor-ß1 were observed around vessel walls in groups 4 and 5. CONCLUSIONS: These findings suggest that coadministration of ASCs and control-released bFGF facilitates angiogenesis in terms of vessel maturation in a murine ischemic hind limb model.

Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness.

Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells (ASCs) are a particularly attractive autologous cell source for various therapeutic purposes. ASCs retain a high proliferation capacity in vitro and have the ability to undergo extensive differentiation into multiple cell lineages. Moreover, ASCs secrete a wide range of growth factors that can stimulate tissue regeneration. Therefore, the clinical use of ASCs is feasible. However, the potential of ASCs differs depending on the donor's medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells. Therefore, to ensure the success of regenerative medicine, tissue engineering methods must be improved by the incorporation of factors that increase the proliferation and differentiation of stem/progenitor cells when autologous cells are used. Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, has recently been identified as a biological material that could be applied to tissue regeneration. Thus, co-transplantation of ASCs and PRP represents a promising novel approach for cell therapy in regenerative medicine. In this review, we describe the potential benefits of adding PRP to ASCs and preclinical and clinical studies of this approach in various medical fields. We also discuss the mechanisms of PRP action and future cell-based therapies using co-transplantation of ASCs and PRP.

Inflammatory responses and potencies of various lipopolysaccharides from bacteria and cyanobacteria in aquatic environments and water supply systems.

Inflammatory substances derived from indigenous bacteria in aquatic environments or water systems are of great concern. Lipopolysaccharides (LPSs), one of the major inflammatory substances in water, are usually identified using Limurus amoebocyte lysate (LAL) assay on the basis of their endotoxic activity, but endotoxin levels do not accurately represent their inflammatory potency in humans. In this investigation, the cellular endotoxin contents of pure-cultured bacteria/cyanobacteria, which are frequently detected in water sources and distribution systems, and of indigenous bacteria in a river and in biologically activated carbon (BAC) effluent, were investigated. The indigenous bacteria showed the highest endotoxin contents exceeding 10(-3)EU/cell. The LPSs were then purified from those samples, and their inflammatory potencies were examined using a human monocytic cell line. The LPSs from Acinetobacter lwoffii culture, the river water, and the BAC effluent sample revealed a unique cytokine secretion pattern; they induced both IL-8 and TNF-α more strongly than the other tested bacterial LPSs. These results suggest that natural bacterial/cyanobacterial flora in aquatic environments and water distribution systems have the potential to induce relatively strong inflammatory responses in humans; therefore, further accumulation of data on water quality from the perspective of not just endotoxins but inflammatory potency is needed.

Direct and indirect effects of a combination of adipose-derived stem cells and platelet-rich plasma on bone regeneration.

A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro. After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-ß1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo. These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.

Effect of Control-released Basic Fibroblast Growth Factor Incorporated in ß-Tricalcium Phosphate for Murine Cranial Model.

BACKGROUND: ß-Tricalcium phosphate (ß-TCP) is used clinically as a bone substitute, but complete osteoinduction is slow. Basic fibroblast growth factor (bFGF) is important in bone regeneration, but the biological effects are very limited because of the short half-life of the free form. Incorporation in gelatin allows slow release of growth factors during degradation. The present study evaluated whether control-released bFGF incorporated in ß-TCP can promote bone regeneration in a murine cranial defect model. METHODS: Bilateral cranial defects of 4 mm in diameter were made in 10-week-old male Sprague-Dawley rats treated as follows: group 1, 20 µl saline as control; group 2, ß-TCP disk in 20 µl saline; group 3, ß-TCP disk in 50 µg bFGF solution; and group 4, ß-TCP disk in 50 µg bFGF-containing gelatin hydrogel (n = 6 each). Histological and imaging analyses were performed at 1, 2, and 4 weeks after surgery. RESULTS: The computed tomography value was lower in groups 3 and 4, whereas the rate of osteogenesis was higher histologically in group 4 than in the other groups. The appearance of tartrate-resistant acid phosphate-positive cells and osteocalcin-positive cells and disappearance of osteopontin-positive cells occurred earlier in group 4 than in the other groups. CONCLUSIONS: These findings suggest that control-released bFGF incorporated in ß-TCP can accelerate bone regeneration in the murine cranial defect model and may be promising for the clinical treatment of cranial defects.

Comparison of inflammatory responses in human cells caused by lipopolysaccharides from Escherichia coli and from indigenous bacteria in aquatic environment.

The endotoxic activities of lipopolysaccharides (LPSs) in water samples are usually determined using a Limulus amoebocyte lysate (LAL) assay, but it is known that the determined activities do not always represent their inflammatory potency in humans. In this investigation, the inflammatory responses in three different human cells stimulated with Escherichia coli LPS, keratinocyte, CD14(+) monocyte, and THP-1, were compared using cytokine secretion as biomarkers to develop novel in vitro assay systems for detecting changes in inflammatory potencies of endotoxins in aquatic environment. Only THP-1 with 6-h stimulation showed dose-dependent responses in the range of normal endotoxin levels in aquatic environment. Then, the inflammatory potency of environmental LPS, which was purified from river water, was tested using THP-1. The levels and patterns of cytokine secretion after the environmental LPS stimulation were completely different from E. coli LPS. Interleukin 8 (IL-8) secretions after the environmental LPS stimulation were approximately 10-fold higher than those after E. coli LPS stimulation. The environmental LPS also induced much higher levels of TNF-α secretions in THP-1. These results suggest that a diversity of LPS structures in aquatic environment could contribute to stronger and different inflammatory responses. This investigation indicated that the proposed THP-1 assay system could be useful for detecting the changes in inflammatory potencies caused by aquatic bacteria.

Increased riboflavin production from activated bleaching earth by a mutant strain of Ashbya gossypii.

The production of riboflavin from vegetable oil was increased using a mutant strain of Ashbya gossypii. This mutant was generated by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Riboflavin production was 10-fold higher in the mutant compared to the wild-type strain. The specific intracellular catalase activity after 3 d of culture was 6-fold higher in the mutant than in the wild-type strain. For the mutant, riboflavin production in the presence of 40 mM hydrogen peroxide was 16% less than that in the absence of hydrogen peroxide, whereas it was 56% less for the wild-type strain. The isocitrate lyase (ICL) activity of the mutant was 0.26 mU/mg of protein during the active riboflavin production phase, which was 2.6-fold higher than the wild-type strain. These data indicate that the mutant utilizes the carbon flux from the TCA cycle to the glyoxylate cycle more efficiently than the wild-type strain, resulting in enhanced riboflavin production. This novel mutant has the potential to be of use for industrial-scale riboflavin production from waste-activated bleaching earth (ABE), thereby transforming a useless material into a valuable bioproduct.