Abstract
Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we ...show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of
Txndc5
markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFβ1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFβ1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of
Txndc5
mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.
Light detection and ranging (LiDAR) is used to estimate tree, stand, and forest characteristics across large geographic areas. In the province of Nova Scotia, an enhanced forest inventory (EFI) was ...developed to provide high-resolution spatial forest inventory estimates across the landscape. For various forest attributes, independent LiDAR-based relationships were built leading to mathematical and biological inconsistency among forest attribute estimates. A systems approach, composed of allometric equations describing the relationships between volume per unit area, Lorey’s average height, basal area, quadratic mean diameter, and density, is developed to address these inconsistencies. Previous results showed that applying the systems approach provided reasonable and compatible estimates and eliminated inconsistency issues among forest attributes. This study evaluates application of the systems approach applied to eastern Nova Scotia using field data from a network of permanent sample plots and recent LiDAR acquisitions. The independent EFI estimates had inconsistencies of greater than 100% for basal area and implied stand-level form factor. These inconsistencies were eliminated using the systems approach. Results show that the systems approach can be scaled to larger landscape areas and that long-term field data can be leveraged to fit the allometric systems producing mathematically and biologically consistent estimates.
This study aims to explore the expression pattern and prognostic significance of miR-33a in non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy.
MiR-33aexpression in NSCLC was ...analyzed in silico using the GEO database and was subsequently confirmed by quantitative RT-PCR in 147 NSCLC biopsies. Among these, 32 of these biopsies were paired with adjacent non-neoplastic tissues. The survival analysis of NSCLC by Kaplan-Meier estimates was stratified based on miR-33a expression. In addition, multivariate survival analysis in corresponding groups of NSCLC patients was conducted by Cox proportional hazards regression model.
The in silico analysis of miR-33a expression in NSCLC resulted to its down-regulation in different tumor types. The expression level of miR-33a was lower in each grade of NSCLC tumor biopsies than in normal lung tissues. Univariate and multivariate survival analysis further established that low miR-33a expression was an important risk factor for overall survival and disease free survival in NSCLC patients.
Our study implied that miR-33a expression levels may have an essential role in NSCLC progression, and could act as a specific and sensitive biomarker for NSCLC patients who have undergone adjuvant chemotherapy.
Using a two-phase sampling approach with systematic selection of large samples of covariates followed by a sampling with probability proportional to prediction (3P sampling) process to subsample ...field measures of the parameters of interest can be an efficient design to sample larger forest areas. To assist in obtaining predictions for each sample plot consistently and rapidly, we propose using a 360degrees spherical camera. In this study, three covariates derived from spherical images were evaluated: (i) basal area (PBA); (ii) sum of squared heights per hectare (PSHT); and (iii) stem fraction (PSF). These covariates were used to estimate volume. Sample simulations showed no biases in volume estimates for any of the three covariates. Overall, PSF had the lowest standard error percentages across different simulated sample sizes (10% for five subsamples to 2.5% for 50 subsamples), even though it had the lowest correlations with field volume (correlation = 0.30-0.31). This may be a result of the relatively consistent stand conditions within the study site. Based on our results, standard errors of 5% were obtainable with measurement fractions of about 25% of the number of image-based predictions when using PSF or PBA and 75% when using PSHT.
Hsa-MicroRNA-124a-3p (hsa-miR-124-3p) is involved in tumor progression in certain malignant tumors. However, its function and clinical implication in hepatocellular carcinoma (HCC) have not yet been ...illustrated. In this study, we explored the expression and prognostic value of hsa-miR-124-3p in patients with HCC. Hsa-miR-124-3p expression in HCC was analyzed in silico, which was subsequently confirmed by quantitative PCR in 155 HCC biopsy samples. Overall survival (OS) and disease-free survival in HCC patients was evaluated by Kaplan–Meier survival analysis, and univariate and multivariate Cox proportional hazard models were used. The in silico results demonstrated that hsa-miR-124-3p was reduced in cell lines and tissues of HCC, and hsa-miR-124-3p expression was lower in HCC tumor samples than in normal liver tissues. Moreover, a decrease in hsa-miR-124-3p expression was closely correlated with tumor diameter (≥ 5 cm) and number of lesions (multiple). Lower hsa-miR-124-3p expression was shown to be correlated with a shorter OS and poor prognosis in HCC. Our findings demonstrate that hsa-miR-124-3p might be a potential target for the diagnosis and prognosis of HCC.
With 75 known species, the freshwater fish genus Sinocyclocheilus is the largest cavefish radiation in the world and shows multiple adaptations for cave‐dwelling (stygomorphic adaptations), which ...include a range of traits such as eye degeneration (normal‐eyed, micro‐eyed and eyeless), depigmentation of skin, and in some species, the presence of “horns”. Their behavioural adaptations to subterranean environments, however, are poorly understood. Wall‐following (WF) behaviour, where an organism remains in close contact with the boundary demarcating its habitat when in the dark, is a peculiar behaviour observed in a wide range of animals and is enhanced in cave dwellers. Hence, we hypothesise that wall‐following is also present in Sinocyclocheilus, possibly enhanced in eyeless species compared to eye bearing (normal‐/micro‐eyed species). Using 13 species representative of Sinocyclocheilus radiation and eye morphs, we designed a series of assays, based on pre‐existing methods for Astyanax mexicanus behavioural experiments, to examine wall‐following behaviour under three conditions. Our results indicate that eyeless species exhibit significantly enhanced intensities of WF compared to normal‐eyed species, with micro‐eyed forms demonstrating intermediate intensities in the WF distance. Using a mtDNA based dated phylogeny (chronogram with four clades A–D), we traced the degree of WF of these forms to outline common patterns. We show that the intensity of WF behaviour is higher in the subterranean clades compared to clades dominated by normal‐eyed free‐living species. We also found that eyeless species are highly sensitive to vibrations, whereas normal‐eyed species are the least sensitive. Since WF behaviour is presented to some degree in all Sinocyclocheilus species, and given that these fishes evolved in the late Miocene, we identify this behaviour as being ancestral with WF enhancement related to cave occupation. Results from this diversification‐scale study of cavefish behaviour suggest that enhanced wall‐following behaviour may be a convergent trait across all stygomorphic lineages.
Sinocyclocheilus, a genus of 75 species of freshwater cavefish, is an emerging model system in evolutionary studies. We studied a behaviour, called “wall‐following,” where fish stay close to the cave walls in absence of light. We show that eyeless species exhibited heightened wall‐following behaviour compared to their sighted counterparts, with small‐eyed species falling in between. We also mapped this behaviour on a phylogenetic tree, discovering a pattern where cave‐dwelling clades showed stronger wall‐following than free‐living ones. Wall‐following is prevalent in all Sinocyclocheilus species and, given the evolutionary history of the genus, is considered an ancestral behaviour that intensified with cave adaptation.
Cu7S4/reduced graphene oxide (rGO) photocatalysts are attracting increasing interest because of their low cost and environmental friendliness. In this study, Cu7S4/rGO nanocomposites with high ...visible-light photocatalytic activity were successfully synthesized via biological and chemical methods. The prepared Cu7S4/rGO nanocomposites exhibited exceptional photocatalytic activity for methyl green (MG) reduction. In particular, the nanocomposites photocatalyst with A-N (biosynthesis with Na2S as the sulfur source) provided the best photocatalytic performance, and could degrade 98.3% MG within 100 min. Their photocatalytic activity sequence is in the following order: A-N (98.3%) > A-U (biosynthesis with CuSO4 as the copper source) (97.8%) > A-C (biosynthesis with CH4N2S as the sulfur source) (97.7%) > A-180 (96.7%) (chemical synthesis at 180 °C in a steel autoclave) > Cu7S4 (69.8%). After five repeated tests, the photocatalyst used in this study showed excellent stability. The photocatalytic activity enhancement can be attributed to Cu7S4 combined with rGO, which can enhance the active center and increase electron transfer. This study provides a novel method for the preparation of a photocatalyst that can quickly and effectively solve dye pollution, and reduce other pollutants. Additionally, the photocatalyst is expected to be used in the fields of photocatalysis, water decomposition and solar cells.
Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial ...sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (
/
) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in
mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in
mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.
•A relative density measure is developed for two species-rich, complex forests in Taiwan.•A simple relative density management diagram is presented.•Random noise regression corrected the lack of ...species-specific specific gravities values.•Random noise regression augmented low sample sizes.•Random noise regression improved statistical and preserved parameter estimates.
Stand Density Index (SDI) is a numerical value that captures intensity of competition within forest stands. It is a tool for managing density of trees, controlling crown development and maintaining degree of forest health through decisions made on initial planting density and thinning schedules. However, classical Reineke’s SDI (Reineke, 1933) has been found to be unsuitable for mixed species and structurally complex forest stands. Alternative measures of SDI are being explored. Natural forests in Taiwan cover an area of approximately 1.5 million ha with 75% classified as mixed species forests. Current SDI research in Taiwan focuses on single-species natural and plantation forests such as Chamaecyparis formosensis and Cryptomeria japonica forests. No study has investigated and developed SDI for mixed species natural forests in Taiwan. Because management of these forests is crucial for conservation and protection against soil erosion, it is necessary to develop SDI for these forests to establish management guidelines. Therefore, relative SDI was developed for cypress- and pine-dominated forests using data from the 4th Taiwan National Forest Inventory following the approach by Ducey and Knapp (2010) which uses intersections between the mixed-species equation and previously-published density equations to establish a relative SDI model. Plots with at least 30% of basal area per hectare of target species were used for model fitting. During model fitting, it was discovered that the lack of species-specific specific gravity estimates played an important role in model significance. Lastly, three different relative SDI models for each forest type were produced that provide preliminary estimates of minimum, mean and maximum relative SDI for forest stands. The major result from this study was that relative SDI could be tentatively calculated and graphically presented for the mixed-species and structurally complex cypress and pine forests that allows a manager to design silvicultural strategies to meet forest management objectives.
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