Aims/hypothesis
As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy.
Methods
Abundance of miR-21 was examined ...in diabetic kidneys from
db/db
mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in
db/db
mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21.
Results
In
db/db
mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with
db/m
+
mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of
db/db
mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting
Smad7
may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways.
Conclusions/interpretation
Inhibition of miR-21 might be an effective therapy for diabetic nephropathy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
► A metal hydrogen storage vessel equipped with finned heat pipes. ► Effects of heat pipes were shown experimentally using LaNi5 as the storage media. ► The absorption time was reduced more than half ...compared to that without heat pipe. ► The desorption time for hydrogen discharge was increased by 44%.
Heat transfer is a critical factor affecting the performance of metal hydrogen storage tanks. Many studies have proposed inner tubular heat exchangers for increasing the heat transfer rate between the metal powders and the exterior environment of the tanks. However, connecting cooling and heating fluid tubes to the storage tanks can be a tedious task, especially for large-scale hydrogen storage systems with a large array of tanks. This study presents a novel design for a metal hydride vessel equipped with heat pipes. These heat pipes enhance heat transfer for hydrogen charge and discharge without the need for tubing through the metal bed. This study experimentally demonstrates the effects of using heat pipes to enhance heat transfer in a hydrogen storage tank using LaNi5 as the storage media and comparing tanks with and without heat pipes. Results show that heat pipes can enhance the hydrogen storage rates in both absorption and desorption. The absorption time was reduced more than half with a 10atm hydrogen supply pressure, and the desorption time for hydrogen discharge at 1L/min was increased by 44%.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background. The present study tested the hypothesis that disruption of Smad7 function may accelerate renal fibrosis and inflammation. Methods. This was investigated in a unilateral ureteral ...obstruction (UUO) model induced in wild-type (WT) and Smad7ΔE1 mice in which functional Smad7 is disrupted by deleting exon I in the Smad7 gene. Renal fibrosis and inflammation after UUO were examined by histology, real-time PCR, western blot analyses and immunohistochemistry. Results. Seven days after UUO, severe tubulointerstitial fibrosis developed in WT mice as evidenced by a marked increase in α-SMA, collagen I and III extracellular matrix. This was associated with a significant upregulation of renal TGF-β1 and CTGF and activation of Smad2/3. Interestingly, compared to WT UUO mice, Smad7ΔE1 mice with UUO exhibited a further increase in TGF-β/Smad2/3-dependent renal fibrosis. Moreover, compared to WT UUO mice, deletion of the Smad7 gene also sustained NF-κB activation and thus enhanced further renal inflammation such as macrophage infiltration and upregulation of TNF-α, MCP-1, OPN and ICAM-1. Conclusion. Smad7 is a critical negative regulator of TGF-β/Smad2/3 and NF-κB signalling and plays a negative regulating role in both renal fibrosis and inflammation after UUO. Results from this study further support the notion that Smad7 may be a therapeutic agent for kidney diseases.
•Particle formation from solute precipitation of a liquid droplet was investigated using a simulative approach.•A model comprises the same and full set of equations that account for the entire ...process of droplet drying.•The volume of fluid method was adopted to capture the gas–liquid–solid interfaces.•The particle produced manifests either a solid or hollow structure as part of the solution determined by the operating conditions.•The influence of ambient temperature on the final structure of the precipitate particle was studied.
The formation of solid and hollow particles from solute precipitation of a liquid droplet was investigated using a simulative approach. The simulation model describes the evolution of the solute concentration, temperature gradient, and size change of the droplet and includes the vapor concentration and temperature gradient in the air surrounding the droplet. The volume of fluid (VOF) method was adopted to capture the gas–liquid–solid interface. The entire drying process was analyzed using a sodium chloride aqueous droplet as an example. The influence of ambient temperature on the final structure of the precipitate particle was studied. Two distinct particle structures were discussed. The droplet solidifies into a solid particle when the ambient temperature is low, and into a hollow shape when the ambient temperature is high. The mechanisms underlying these two particle structures were discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The use of direct-write dip-pen nanolithography (DPN) to generate covalently anchored, nanoscale patterns of oligonucleotides on both metallic and insulating substrates is described. Modification of ...DNA with hexanethiol groups allowed patterning on gold, and oligonucleotides bearing 5′-terminal acrylamide groups could be patterned on derivatized silica. Feature sizes ranging from many micrometers to less than 100 nanometers were achieved, and the resulting patterns exhibited the sequence-specific binding properties of the DNA from which they were composed. The patterns can be used to direct the assembly of individual oligonucleotide-modified particles on a surface, and the deposition of multiple DNA sequences in a single array is demonstrated.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
South East Asia has the highest rate of lowland forest loss of any tropical region, with logging and deforestation for conversion to plantation agriculture being flagged as the most urgent threats. ...Detecting and mapping logging impacts on forest structure is a primary conservation concern, as these impacts feed through to changes in biodiversity and ecosystem functions. Here, we test whether high-spatial resolution satellite remote sensing can be used to map the responses of aboveground live tree biomass (AGB), canopy leaf area index (LAI) and fractional vegetation cover (FCover) to selective logging and deforestation in Malaysian Borneo. We measured these attributes in permanent vegetation plots in rainforest and oil palm plantations across the degradation landscape of the Stability of Altered Forest Ecosystems project. We found significant mathematical relationships between field-measured structure and satellite-derived spectral and texture information, explaining up to 62% of variation in biophysical structure across forest and oil palm plots. These relationships held at different aggregation levels from plots to forest disturbance types and oil palms allowing us to map aboveground biomass and canopy structure across the degradation landscape. The maps reveal considerable spatial variation in the impacts of previous logging, a pattern that was less clear when considering field data alone. Up-scaled maps revealed a pronounced decline in aboveground live tree biomass with increasing disturbance, impacts which are also clearly visible in the field data even a decade after logging. Field data demonstrate a rapid recovery in forest canopy structure with the canopy recovering to pre-disturbance levels a decade after logging. Yet, up-scaled maps show that both LAI and FCover are still reduced in logged compared to primary forest stands and markedly lower in oil palm stands. While uncertainties remain, these maps can now be utilised to identify conservation win–wins, especially when combining them with ongoing biodiversity surveys and measurements of carbon sequestration, hydrological cycles and microclimate.
•Map degradation of forests in Borneo based on biophysical attributes•Linking RapidEye-derived reflectance and texture data to field measured structure•Beta-logistic regression models explained up to 62% of structure variation.•Up-scaled maps reveal high spatial variation in the impacts of previous logging.•Maps will be utilised to identify high-conservation-value forests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Cryptococcosis is caused by either Cryptococcus neoformans or C. gattii. While cryptococcal meningoencephalitis is caused mostly by C. neoformans in immunocompromised patients, the risk factors ...remain unclear for patients with no known immune defect. Recently, anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies were detected in the plasma of seven "immunocompetent" cryptococcosis patients, and the cryptococcal strains from these patients were reported as C. neoformans (three strains), C. gattii (one strain), and Cryptococcus (three strains not identified to the species level). We identified all three strains that had not been identified to the species level as C. gattii. Notably, the three strains that were reported as C. neoformans but were unavailable for species confirmation originated from Sothern California and Thailand where C. gattii is endemic. Most clinical laboratories designate C. neoformans without distinguishing between the two species; hence, these three strains could have been C. gattii. Since C. gattii infects more immunocompetent patients than C. neoformans, we pursued the possibility that this antibody may be more prevalent in patients infected with C. gattii than in those infected with C. neoformans. We screened the plasma of 20 healthy controls and 30 "immunocompetent" patients with cryptococcal meningoencephalitis from China and Australia (multiple ethnicities). Anti-GM-CSF autoantibodies were detected only in the plasma of seven patients infected by C. gattii and one healthy volunteer and in none infected by C. neoformans. While plasma from these C. gattii patients completely prevented GM-CSF-induced p-STAT5 in normal human peripheral blood mononuclear cells (PBMCs), plasma from one healthy volunteer positive for anti-GM-CSF autoantibodies caused only partial blockage. Our results suggest that anti-GM-CSF autoantibodies may predispose otherwise immunocompetent individuals to meningoencephalitis caused by C. gattii but not necessarily to that caused by C. neoformans. IMPORTANCE Cryptococcal meningoencephalitis is the most serious central nervous system (CNS) infection caused by Cryptococcus neoformans or C. gattii. Cryptococcus primarily infects immunocopromised patients but is also sporadically encountered in otherwise "immunocompetent" patients with no known risk. In a recent study, anti-GM-CSF autoantibodies were detected in the plasma of seven otherwise immunocompetent patients with cryptococcal meningoencephalitis. Four of seven (57%) cryptococcal isolates from these patients were identified as C. gattii, while three strains were unavailable for species confirmation. We collected plasma from 30 otherwise healthy patients with CNS cryptococcosis in China and Australia (multiethnic) and analyzed the samples for the presence of anti-GM-CSF autoantibodies. The results suggest that anti-GM-CSF autoantibodies are a risk factor for CNS infection by C. gattii but not C. neoformans. GM-CSF may have a specific role in host defense against C. gattii, thereby elevating the importance of determining the level of anti-GM-CSF autoantibodies which can impact clinical management.
Alzheimer's disease (AD) and vascular dementia are the major causes of cognitive disorders worldwide. They are characterized by cognitive impairments along with neuropsychiatric symptoms, and that ...their pathogeneses show overlapping multifactorial mechanisms. Although AD has long been considered the most common cause of dementia, individuals afflicted with AD commonly exhibit cerebral vascular abnormalities. The concept of mixed dementia has emerged to more clearly identify patients with neurodegenerative phenomena exhibiting both AD and cerebral vascular pathologies-vascular damage along with β-amyloid (Aβ)-associated neurotoxicity and τ-hyperphosphorylation. Cognitive impairment has long been commonly explained through a 'neuro-centric' perspective, but emerging evidence has shed light over the important roles that neurovascular unit dysfunction could have in neuronal death. Moreover, accumulating data have been demonstrating astrocytes being the essential cell type in maintaining proper central nervous system functioning. In relation to dementia, the roles of astrocytes in Aβ deposition and clearance are unclear. This article emphasizes the multiple events triggered by ischemia and the cytotoxicity exerted by Aβ either alone or in association with endothelin-1 and receptor for advanced glycation end products, thereby leading to neurodegeneration in an 'astroglio-centric' perspective.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•A high-and-rapid-response capacitive humidity sensor of AAO is made from low-cost commercial 1050 Al alloy.•Performance is enhanced by increasing water adsorption ratio and electrode area of AAO ...with lower thickness.•Large-area AAO increases the capacitance value to 984.2 nF at RH 80 % for a much higher S/N ratio.•AAO at 20 V provides larger adsorption ratio for higher response of 5013 % about 3.5 time the 40 V one.•The shallow pores benefit to reduce response-recovery time to 9–11 s due to shorter diffusion distance.
Anodic aluminum oxide (AAO) is a well-known nanoporous material and a template for nanotechnology application. The AAO based humidity sensor is traditionally fabricated using low-temperature (0–10 °C) two-step anodization in oxalic acid at 40 V from the expensive high-purity aluminum of small-area as well with low response and low intensity. Here, one-step anodizing commercial large-area low-purity aluminum 1050 alloy was realized for high-performance humidity sensor by hybrid-pulse anodization in 0.3 M oxalic acid at 20 V at 25 °C that merits low cost, short fabrication time and high-and-rapid capacitive response. The performance enhancement is attributed to the increased total pore area adsorption ratio and the electrode area of AAO with lower thickness to make much more water vapor molecules adsorb onto the wall surface of pores for sensing with high capacitance, response and short response-recovery time. The low-thickness pores make water molecules adsorb onto and desorb from the pores surface more quickly because of shorter diffusion path. Also, a small-area sample of traditional 40 V AAO is used as a reference for comparison. A shorter anodization time of 55 min is also fabricated for understanding the thickness effect on the response-recovery time. The large-area AAO humidity sensor of 16 cm2 at 20 V exhibits high response (above 5000 %, 3.5 times the traditional reference) and quick response-recovery time (9 s). The high-and-rapid-response enhancement mechanism of AAO capacitive humidity sensor is established.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We sought to define age-related geometric changes of the aortic arch and determine their relationship to central aortic stiffness and left ventricular (LV) remodeling.
The proximal aorta has been ...shown to thicken, enlarge in diameter, and lengthen with aging in humans. However, no systematic study has described age-related longitudinal and transversal remodeling of the aortic arch and their relationship with LV mass and remodeling.
We studied 100 subjects (55 women, 45 men, average age 46 ± 16 years) free of overt cardiovascular disease using magnetic resonance imaging to determine aortic arch geometry (length, diameters, height, width, and curvature), aortic arch function (local aortic distensibility and arch pulse wave velocity PWV), and LV volumes and mass. Radial tonometry was used to calculate central blood pressure.
Aortic diameters and arch length increased significantly with age. The ascending aorta length increased most, with age leading to aortic arch widening and decreased curvature. These geometric changes of the aortic arch were significantly related to decreased ascending aortic distensibility, increased aortic arch PWV (p < 0.001), and increased central blood pressures (p < 0.001). Increased ascending aortic diameter, lengthening, and decreased curvature of the aortic arch (unfolding) were all significantly associated with increased LV mass and concentric remodeling independently of age, sex, body size, and central blood pressure (p < 0.01).
Age-related unfolding of the aortic arch is related to increased proximal aortic stiffness in individuals without cardiovascular disease and associated with increased LV mass and mass-to-volume ratio independent of age, body size, central pressure, and cardiovascular risk factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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