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Recently, cognitive impairments (CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35 ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with CI and patients with normal cognition (CN). We found altered gut microbial communities and a lower ratio of Firmicutes/ Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future. [ABSTRACT FROM AUTHOR]

In this study, low-iron Zn–Fe alloy coatings and pure Zn coatings, with or without trivalent chromium passivation treatment, were electrodeposited onto a sintered NdFeB magnet from a weak acid chloride bath. The surface morphology and structure of the coatings were then examined using the X-ray diffraction, a scanning electron microscope and 3D white-light interfering surface analysis. Meanwhile, the electrodeposition behavior and anti-corrosive properties of the coatings were investigated using cyclic voltammetry, potentiodynamic polarization, electrochemical impedance spectroscopy, and natural salt spray tests. The results indicate that a passivated Zn–Fe alloy coating with a 0.9 wt.% Fe content provided much better corrosion resistance than a pure Zn coating and could provide both anodic protection and physical barrier function in the NdFeB substrates. The Fe element in Zn–Fe alloy coating was predominantly in solid solution in η-phase and small amounts in elemental form, which was beneficial to acquire a compact coating and passivation film. Finally, the passivated Zn–Fe alloy coating withstood 210 h against a neutral 3.5 wt.% NaCl salt spray without any white rust, which was 3–4 times longer than the pure Zn coating. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons (MNs). Previously, studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia. And oligodendrocytes (OLs) have only recently been highlighted. Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells (OPCs) was observed in ALS patients. The selective ablation of mutant SOD1 (the dysfunctional superoxide dismutase) from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model (SOD1G37R). In this study, we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS. Particularly, we examined the insufficient local energy supply from OLs to axons, impaired differentiation from OPCs into OLs mediated by oxidative stress damage, and inflammatory injury to the OLs. Since increasing evidence depicted that ALS is not a disease limited to MNs damage, exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets. [ABSTRACT FROM AUTHOR]

The ultrafine grain with the effective grain size of 1.10 μm was fabricated by intercritical deformation on low-carbon microalloyed steel, which was finer than the deformation induced ferrite transformation (DIFT) at 1.55 μm. During intercritical deformation, the DIFT process was enhanced, showing a colony distribution of the refined grains. Meanwhile, the continuous dynamic recrystallization of pro-eutectoid ferrite was developed by both the subgrains progressively trapping dislocations and the serrated boundary pinching off the elongated grains. These processes were directly observed through the grain average misorientation maps of electron back-scattered diffraction and confirmed by transmission electron microscopy micrographs. [ABSTRACT FROM AUTHOR]

Computer vision provides a real-time, non-destructive, and indirect way of horticultural crop yield estimation. Deep learning helps improve horticultural crop yield estimation accuracy. However, the accuracy of current estimation models based on RGB (red, green, blue) images does not meet the standard of a soft sensor. Through enriching more data and improving the RGB estimation model structure of convolutional neural networks (CNNs), this paper increased the coefficient of determination (R2) by 0.0284 and decreased the normalized root mean squared error (NRMSE) by 0.0575. After introducing a novel loss function mean squared percentage error (MSPE) that emphasizes the mean absolute percentage error (MAPE), the MAPE decreased by 7.58%. This paper develops a lettuce fresh weight estimation method through the multi-modal fusion of RGB and depth (RGB-D) images. With the multimodal fusion based on calibrated RGB and depth images, R2 increased by 0.0221, NRMSE decreased by 0.0427, and MAPE decreased by 3.99%. With the novel loss function, MAPE further decreased by 1.27%. A MAPE of 8.47% helps to develop a soft sensor for lettuce fresh weight estimation. [ABSTRACT FROM AUTHOR]

In this paper, the welding thermal cycle process of deep-sea pipeline steel was investigated by welding thermal simulation. The microstructure evolution, crystallology and second-phase precipitation behavior of the soft zone of the heat-affected zone (HAZ) were characterized and analyzed by combining scanning electron microscopy, electron back-scattered diffraction, transmission electron microscopy and hardness testing. The results show that HAZ softening appeared in the fine-grained zone with a peak temperature of 900–1000 °C for deep-sea pipeline steel, the base metal microstructure of which was the polygonal ferrite and acicular ferrite. Using V microalloying and low welding heat input could effectively decrease the softening of the HAZ fine-grained region, which was achieved by reducing the effective grain size, increasing the proportion of the dislocation substructures, and precipitating the nanoscale second-phase particles. [ABSTRACT FROM AUTHOR]

In the transition towards green energy, long distance transportation of gaseous hydrogen by pipeline is considered to be an economically attractive solution. For safe transportation of hydrogen, it is important to conduct relevant mechanical tests in representative hydrogen environments and working conditions of pipelines to demonstrate acceptable hydrogen embrittlement resistance of the steel. One important issue is the testing condition for the ratio of gaseous hydrogen volume over specimen surface area required in mechanical testing since this has not been specified in any testing standards and codes or investigated. This study investigated this issue by performing slow strain rate tensile (SSRT) testing of an X52 pipeline steel in gaseous hydrogen with different ratios of hydrogen volume/specimen surface area, R v/s , ml/mm2. It was found that, with increasing R v/s ratio, the area reduction of the steel decreased and hydrogen embrittlement sensitivity increased in the range of the R v/s ratios investigated. The saturating R v/s ratio appeared to be ∼2.0 beyond which the effect of R v/s ratio on hydrogen embrittlement sensitivity was relatively small. The macroscopic and microscopic observations on both the fracture and side surfaces of the SSRT tested specimens also found that the tendency to cleavage fracture increased with increasing R v/s ratio. The results of the ab initio molecular dynamics (AIMD) simulations performed also predicted a dependence of hydrogen embrittlement on hydrogen volume when R v/s ratio is relatively small. • The effect of the ratio of gaseous hydrogen volume over specimen surface area, R v/s , on HE was investigated the first time in the world. • The threshold R v/s ratio, beyond which the influence of the R v/s ratio on hydrogen embrittlement sensitivity is small, was determined. • Tendency to cleavage fracture increased with increasing R v/s ratio. • The increased tendency to hydrogen embrittlement under higher R v/s ratios was verified by the AIMD simulations. [ABSTRACT FROM AUTHOR]

The effect of intercritical annealing temperature (IAT) on the multiphase microstructure evolution of 0.02C-7Mn steel was investigated using scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), X-ray diffraction (XRD), and transmission electron microscope (TEM), as well as Thermo-Calc and Dictra software simulations. The results indicated that an hexagonal closed-packed phase (ε-martensite) mainly appeared on reversed austenite by air cooling after the steel was annealed between 650 °C to 675 °C for 1 h. The multiphase microstructure contained retained austenite (RA), athermal ε-martensite, annealed martensite, and athermal α-martensite, but both their content and morphology strongly depended on the IAT. In contrast to athermal ε-martensite, RA mainly existed after annealing at 600 °C to 650 °C. The maximum volume fraction of RA is 24.32% after annealing at 650 °C, while it was 28.54% for athermal ε-martensite after annealing at 675 °C. RA displayed a granular and thin lath-like morphology after annealing at 620 °C and a larger granular and coarse lath-like morphology after annealing at 650 °C. The athermal ε-martensite morphology was granular and lath-like at 650 °C, and block-like at 675 °C. Decreasing the C and Mn contents, and increasing the lath size of reversed austenite decreased the thermal stability and the stacking fault energy (SFE), which induced martensitic transformation with increasing IAT. As a result, the reversed austenite remained at low IAT, transformed into athermal ε-martensite at medium IAT, and induced athermal α-martensite at high IAT. • A thermal ε-martensite appeared during the air cooling of reversed austenite in 0.02C-7Mn steel. • Content and morphology of multiphase microstructure strongly depended on the annealing temperature. • The decreasing and heterogeneousC and Mn decreased thermal stability, which induced martensitic transformation. • Athermal martensitic transformation was due to the negativeSFE (n=2). [ABSTRACT FROM AUTHOR]

Background: Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, diferentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. Results: We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium infux and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3−/− mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3−/− mice exhibit the reverse efect. Conclusions: We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may afect multiple tissues, including the brain [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most widespread neurodegenerative disorder in the world. It has been reported that exosomes derived from mesenchymal stem cells (MSCs) can contribute to the recovery of PD. However, the underlying mechanism remains poorly defined. In this study, proteomics and time-series analysis showed that exosomes derived from MSCs can keep human brain microvascular endothelial cells (HBMECs) in a transcriptionally active state, which may be beneficial for angiogenesis. Next, we found that MSCderived exosomes can promote the angiogenesis of HBMECs by increasing the expression of ICAM1, and alleviate the damage caused by 1-methyl-4-phenylpyridinium (MPP+) in these cells. Accordingly, when ICAM1 was knocked down, the tube formation ability of HBMECs was obviously decreased. In addition, ICAM1 was found to promote the angiogenesis of HBMECs by activating the SMAD3 and P38MAPK signaling pathways. In a PD mouse model, MSC-derived exosomes were found to contribute to the recovery of PD by promoting ICAM1-related angiogenesis. These findings demonstrate that the exosome-ICAM1-SMAD3/P38MAPK axis can promote the angiogenesis of HBMECs, with possible therapeutic potential for PD. [ABSTRACT FROM AUTHOR]

The effect of both Nb content and heat input on the softening phenomenon of the heat-affected zone (HAZ) of low-alloy high-strength steel was studied through welding thermal simulation experiments. The microstructure evolution, density variation of geometrically necessary dislocation, microhardness distribution and the second phase precipitation behavior in HAZ was characterized and analyzed by combining the optical microscope, scanning electron microscope, high-resolution transmission electron microscope with microhardness tests. The results showed that the softening appeared in the fine-grain HAZ (FGHAZ) of the low-alloy high-strength steel with the polygonal ferrite and bainite microstructure. With an increase in Nb content, the FGHAZ softening was inhibited even with high heat input; however, the hardness shows little variation. On the one hand, the increase in the Nb content increased the volume fraction of high-strength bainite in the FGHAZ. On the other hand, the remarkable strengthening was produced by the equally distributed precipitation nanoparticles. As a result, the two factors were the main reason for the solution of the FGHAZ softening problem in the low-alloyed high-strength steel with the mixed microstructure of ferrite and bainite. [ABSTRACT FROM AUTHOR]

Metastasis is the major cause of death in colorectal cancer (CRC) patients. Inhibition of metastasis will prolong the survival of patients with CRC. Cancer cells bring their own soil, cancer-associated fibroblasts (CAFs), to metastasize together, promoting the survival and colonization of circulating cancer cells. However, the mechanism by which CAFs metastasize remains unclear. In this study, CAFs were derived from adipose mesenchymal stem cells (MSCs) after co-culture with CRC cell lines. Transwell assays showed that CAFs have stronger migration and invasion abilities than MSCs. In a nude mouse subcutaneous xenograft model, CAFs metastasized from the primary tumour to the lung and promoted the formation of CRC metastases. The expression of HIF-1α was upregulated when MSCs differentiated into CAFs. Inhibition of HIF-1α expression inhibited the migration and invasion of CAFs. Western blot and ChIP assays were used to identify the genes regulated by HIF-1α. HIF-1α regulated the migration and invasion of CAFs by upregulating miR-210 transcription. Bioinformatics analysis and luciferase reporter assays revealed that miR-210 specifically targeted the 3'UTR of VMP1 and regulated its expression. Downregulation of VMP1 enhanced the migration and invasion of CAFs. In vivo, inhibition of miR-210 expression in CAFs reduced the metastasis of CAFs and tumour cells. Therefore, the HIF-1α/miR-210/VMP1 pathway might regulate the migration and invasion of CAFs in CRC. Inhibition of CAF metastasis might reduce CRC metastasis. [ABSTRACT FROM AUTHOR]

Angiogenesis is a complicated and sequential process that plays an important role in different physiological processes. Mesenchymal stem cells (MSCs), which are pluripotent stem cells, are widely used for the treatment of ischemic and traumatic diseases, and exosomes derived from these cells can also promote angiogenesis. Therefore, we aimed to uncover mechanisms to improve MSC exosome-mediated angiogenesis. For this study, we isolated human adipose-derived MSCs (hAD-MSCs) and assessed differentiation ability and markers. Cells were divided into hypoxia-treated MSCs (H-MSCs) and normoxia-treated MSCs (N-MSC), and exosomes were extracted by ultrafiltration. Exosomes (100 μg/mL) from H-MSCs and N-MSCs were added to human umbilical vein endothelial cells (HUVECs). Exosome uptake and the ability of endothelial cells to form tubes were detected in real time. Protein samples were collected at different time points to detect the expression of inhibitors (Vash1) and enhancers (Angpt1 and Flk1) of angiogenesis; we also assessed their related signaling pathways. We found that exosomes from the hypoxia group were more easily taken up by HUVECs; furthermore, their angiogenesis stimulatory activity was also significantly enhanced compared to that with exosomes from the normoxia group. HUVECs exposed to exosomes from H-MSCs significantly upregulated angiogenesis-stimulating genes and deregulated angiogenesis-inhibitory genes. The expression of vascular endothelial growth factor (VEGF) and activation of the protein kinase A (PKA) signaling pathway in HUVECs were significantly increased by hypoxia-exposed exosomes. Moreover, a PKA inhibitor was shown to significantly suppress angiogenesis. Finally, we concluded that hypoxia-exposed exosomes derived from hAD-MSCs can improve angiogenesis by activating the PKA signaling pathway and promoting the expression of VEGF. These results could be used to uncover safe and effective treatments for traumatic diseases. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact. However, the relationship between these markers and the severity of dementia, as well as the development of the disease, should be further studied. Objective: Compare the CSF level of total tau (T-tau) and phosphorylated tau at threonine 231 ( P-tau231 ) between patients with moderate to severe Alzheimer's disease (AD) and those with vascular dementia (VD) at baseline, and 6 month follow-up. Observe the differences between patients with AD and control group, as well as the changes as the disease develops. Methods: There were 11 patients with moderate AD (10 ≤ MMSE ≤ 20), 10 patients with severe AD (MMSE ≤ 9), and 7 age-matched patients with severe VD at baseline, among which 7 AD patients and 6 VD patients completed the 6 months follow-up. CSF levels of T-tau, P-tau231 were measured with sandwich ELISA. Result: At baseline, the concentrations of the CSF level of T-tau were 470.08 (263.58) pg/mL in the AD group and 208.76 (42.24) pg/mL in the VD group. This difference was statistically significant (Z= -3.369, p <0.001). The concentrations of CSF level of P-tau231 were 90.94 (49.86) pg/mL in the AD group and 42.96 (13.10) pg/ mL in the VD group. This difference was also statistically significant (Z = -3.237, p <0.001). Compared to patients with severe VD, the concentration of CSF T-tau in patients with severe AD was significantly higher (Z= -2.830, p = 0.005), as well as the concentration of CSF P-tau231 (Z = -2.392, p = 0.017). The concentration of CSF P-tau231 in the patients with moderate AD was significantly higher than that in the patients with severe VD (Z = -2.605, p = 0.009). At the 6 months follow-up, there were no statistically significant differences in the changes of CSF T-tau and CSF P-tau231 concentrations between the AD group and VD group. Conclusion: The CSF level of T-tau and P-tau231 in the AD patients was significantly higher than that in the VD patients. The concentration of CSF P-tau231 in the moderate AD patients was significantly higher than that in the patients with severe AD. During the 6 months follow-up, the changes of the CSF concentrations of T-tau and P-tau231 between AD group and VD group were not statistically significant. [ABSTRACT FROM AUTHOR]

In this study, the series temperature Charpy impact and drop-weight tear test (DWTT) were investigated, the misorientation angles among structural boundaries where the cleavage crack propagated were identified, and angles of {100} cleavage planes between adjacent grains along the cleavage crack propagated path were calculated in five directions (0°, 30°, 45°, 60°, and 90° to the rolling direction) of high-grade pipeline steel. Furthermore, the effective grain size (grain with misorientation angles greater than 15°) was redefined, and the quantitative influences of the redefined effective grain size on Charpy impact and DWTT is also discussed synthetically. The results showed that the microstructure presented a typical acicular ferrite characteristic with some polygonal ferrite and M-A islands (composed of martensite and retained austenite), and the distribution of the high-angle grain boundaries were mainly distributed in the range of 45°–65° in different directions. The Charpy impact energy and percent shear area of DWTT in the five directions increased with refinement of the redefined effective grain size, composed of grains with {100} cleavage planes less than 35° between grain boundaries. The ductile-to-brittle transition temperature also decreased with the refining of the redefined effective grain size. The redefined effective grain boundaries can strongly hinder fracture propagation through electron backscattered diffraction analysis of the cleavage crack path, and thus redefined effective grain can act as the effective microstructure unit for cleavage. [ABSTRACT FROM AUTHOR]