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Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Abstract PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.

The impact of contact between two elastic–plastic bodies is highly complex, with no established theoretical contact model currently available. This study investigates the problem of an elastic–plastic sphere impacting an elastic–plastic half-space at low speed and low energy using the finite element method (FEM). Existing linear contact loading laws exhibit significant discrepancies as they fail to consider the impact of elasticity and yield strength on the elastic–plastic sphere. To address this limitation, a novel linear contact loading law is proposed in this research, which utilizes the concept of equivalent contact stiffness rather than the conventional linear contact stiffness. The theoretical expressions of this new linear contact loading law are derived through FEM simulations of 150 sphere and half-space impact cases. The segmental linear characteristics of the equivalent contact stiffness are identified and fitted to establish the segmental expressions of the equivalent contact stiffness. The new linear contact loading law is dependent on various factors, including the yield strain of the half-space, the ratio of elastic moduli between the half-space and sphere, and the ratio of yield strengths between the half-space and sphere. The accuracy of the proposed linear contact loading law is validated through extensive Finite Element Method simulations, which involve an elastic–plastic half-space being struck by elastic–plastic spheres with varying impact energies, sizes, and material combinations.

Beryllium resources in China are concentrated in Xinjiang, Inner Mongolia, Sichuan and Yunnan, mainly including two types: granite pegmatite and aerogenetic hydrothermal vein. Associated beryllium resources are the majority, while beryllium consumption depends heavily on imports. Thus, strengthening the technical research on beneficiation and comprehensive utilization of domestic beryllium resources, realizing its efficient and reasonable development are significant measures to ensure the safety of those resources. This paper introduces the current situation of domestic beryllium resources, including general situation, types, distribution, development and utilization, mineral processing technology and reagents, expounds the core problems and solutions in the process of beryllium ore beneficiation, and puts forward that the research on new high-efficiency flotation reagents is the technical key to improve the beneficiation index of beryllium ore. Simultaneously, in view of the reality of low grade and multiple coassociated valuable components of beryllium ore in China, it is pointed out that the cascade comprehensive utilization of resources is an important direction for the development of beryllium ore beneficiation.

Abstract Visualizing latent evidence at a crime scene has gained popularity in the field of forensic science during the past few years. Thus, this study designs and develops a one-click device for the rapid visualization and extraction of latent evidence through multimodal light source integration and light-guiding technology. Our device exhibits multispectral and angle timing functions for storing the captured evidence images. Furthermore, the geometric registration, feature extraction, feature optimization, and feature integration of the evidence images are processed by a backend system, and the images are then presented. Overall, this study enhances the standard and the technical content of evidence extraction and simplifies the evidence extraction process. In addition to the rapid handling of the scenes captured at a crime scene, the one-click device has other notable advantages, such as fast imaging, portability, being independent of the environmental conditions and the operator’s technical capabilities, and zero pollution to ensure the repeatability of material evidence extraction. Compared with the original optical forensics equipment, the spectrum and angle of our system are more extensive.

Objective: It is indisputable that the functional connectivity of the brain network in juvenile myoclonic epilepsy (JME) patients is abnormal. As a mathematical extension of the traditional network model, the multilayer network can fully capture the fluctuations of brain imaging data with time, and capture subtle abnormal dynamic changes. This study assumed that the dynamic structure of JME patients is abnormal and used the multilayer network framework to analyze the change brain community structure in JME patients from the perspective of dynamic analysis.Methods: First, functional magnetic resonance imaging (fMRI) data were obtained from 35 JME patients and 34 healthy control subjects. In addition, the communities of the two groups were explored with the help of a multilayer network model and a multilayer community detection algorithm. Finally, differences were described by metrics that are specific to the multilayer network.Results: Compared with healthy controls, JME patients had a significantly lower modularity degree of the brain network. Furthermore, from the level of the functional network, the integration of the default mode network (DMN) and visual network (VN) in JME patients showed a significantly higher trend, and the flexibility of the attention network (AN) also increased significantly. At the node level, the integration of seven nodes of the DMN was significantly increased, the integration of five nodes of the VN was significantly increased, and the flexibility of three nodes of the AN was significantly increased. Moreover, through division of the core-peripheral system, we found that the left insula and left cuneus were core regions specific to the JME group, while most of the peripheral systems specific to the JME group were distributed in the prefrontal cortex and hippocampus. Finally, we found that the flexibility of the opercular part of the inferior frontal gyrus was significantly correlated with the severity of JME symptoms.Conclusion: Our findings indicate that the dynamic community structure of JME patients is indeed abnormal. These results provide a new perspective for the study of dynamic changes in communities in JME patients.

In this study, silicon coating was deposited on melt-infiltrated SiC composites using atmospheric plasma spraying and then annealed at 1100 and 1250 °C for 1–10 h to investigate the effect of annealing on the layer. The microstructure and mechanical properties were evaluated using scanning electron microscopy, X-ray diffractometry, transmission electron microscopy, nano-indentation, and bond strength tests. A silicon layer with a homogeneous polycrystalline cubic structure was obtained without phase transition after annealing. After annealing, three features were observed at the interface, namely β-SiC/nano-oxide film/Si, Si-rich SiC/Si, and residual Si/nano-oxide film/Si. The nano-oxide film thickness was ≤100 nm and was well combined with SiC and silicon. Additionally, a good bond was formed between the silicon-rich SiC and silicon layer, resulting in a significant bond strength improvement from 11 to >30 MPa.

Abstract Purpose Colon cancer (CC) is a very common gastrointestinal tumor that is prone to invasion and metastasis in the late stage. This study aims to observe the expression of Na+/Ca2+ exchangers (NCXs) and analyze the correlation between NCXs and the prognosis of CC. Methods Specimens of 111 stage II–IV CC patients were collected. We used western blotting, qPCR, and immunohistochemical staining to observe the distributions and expression levels of NCX isoforms (NCX1, NCX2, and NCX3) in CC and distal normal tissues. Cox proportional hazards models were used to assess prognostic factors for patients. Results The expression of NCXs in most tumor specimens was lower than that in normal tissues. The NCX expression levels in tumor tissues from the primary tumor, local lymph node metastasis sites, and distant liver metastasis sites were increasingly significantly lower than those in normal tissues. The results of the Kaplan-Meier survival curves showed that the downregulation of any NCX isoform was closely related to the worse prognosis of advanced CC. Conclusion NCXs can be used as independent prognostic factors for CC. Our research results are expected to provide new targets for the treatment of CC.

Abstract To reduce the friction coefficient of cobalt-cemented tungsten carbide (WC-12Co) wear-resistant coatings, graphene was compounded into WC-12Co powder via wet ball milling and spray granulation. Self-lubricating and wear-resistant graphene coatings were prepared via detonation gun spraying. The presence, morphologies, and phase compositions of graphene in the powders and coatings that are obtained through different powder preparation processes were analyzed. The analysis was performed using the following technologies: energy-dispersive X-ray-spectroscopy (EDXS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The mechanical properties of the coatings were studied using a microhardness tester and a universal drawing machine. The friction and wear properties of the coatings were studied using an SRV-4 friction and wear tester. The results showed that the graphene content in the WC-12Co coating modified with graphene was higher than that without modification; graphene was embedded in the structure in a transparent and thin-layer state. The adhesive strength of this coating at approximately 25 °C was approximately 60.33 MPa, and the hardness was approximately 984 HV0.3. After high-temperature treatment, the adhesive strength and hardness of the graphene oxide (GO)/WC-12Co coating decreased slightly (the lowest adhesive strength of 53.16 MPa was observed after treatment at 400 °C, and the lowest hardness of approximately 837 HV0.3 was observed after treatment at 300 °C). Compared to the friction coefficient (0.6) of the WC-12Co coating obtained at room temperature, the friction coefficient of the GO/WC-12Co coating was decreased by approximately 50% of that value. The graphene-modified coating was continuously exposed to the wear tracks on the surface of the contacting materials during friction, and a lubricating film was formed in the microareas in which the wear tracks were present. The coating exhibited improved self-lubricating and wear-resistant effects compared to the unmodified WC-12Co coating. The results of this study demonstrated that graphene could be effective in self-lubrication and wear-reduction in a temperature range of 100–200 °C, as a friction coefficient of 0.3 was maintained.

Parkinson’s disease (PD) is the second most common neurodegenerative disease, of which the histopathological hallmark is the formation of Lewy bodies consisting of α-synuclein as the major component. α-Synuclein can sequester DNA Methyltransferase 1 (DNMT1), the maintenance DNA methylation enzyme, from the nucleus and into the cytoplasm, leading to global DNA hypomethylation in human brain. As DNA methylation is a major epigenetic modification that regulates gene expression and there is no specific database storing PD associated methylation information, PDmethDB (Parkinson’s Disease Methylation Database) aims to curate PD associated methylation information from literature to facilitate the study of the relationship between PD and methylation. Currently, PDmethDB contains 97,077 PD methylation associated entries among 12,308 molecules, 37,944 CpG sites, 31 tissues and 3 species through a review of about 1600 published papers. This includes information concerning the gene/molecule name, CpG site, methylation alteration, expression alteration, tissue, PMID, experimental method, and a brief description about the entry. PDmethDB provides a user-friendly interface to search, browse, download and submit data. PDmethDB supports browsing by molecule, species, tissue, gene region, methylation alteration and experimental methods. PDmethDB also shows the entry gene interaction network including protein–protein interactions and miRNA-targets interactions with a highlight of PD associated genes from DisGeNET database. PDmethDB aims to facilitate the understanding of the relationship between PD and methylation.Database URL: https://ageing.shinyapps.io/pdmethdb/

To reduce the brittleness of Fe-Al intermetallic compound coatings, FeNiCrAl powder wire for high-speed electric arc spraying is developed by integrating Ni and Cr into an Fe-Al intermetallic compound. The corresponding FeNiCrAl coating is prepared via high-speed electric arc spraying technology. A 3Cr13 coating is selected as the material for comparison, and the friction and wear properties of the two coatings are investigated from 200 °C to 800 °C. The friction coefficient variations and friction surface topography patterns of the two coatings are analyzed via X-ray diffractometry (XRD), hardness testing, and scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS). The phase compositions of the materials on the wear surfaces are analyzed via X-ray photoelectron energy spectrometry (XPS). The results show that after the friction coefficient of the FeNiCrAl coating reaches its peak value at 400 °C, it declines with increasing temperature, and its wear volume is less than that of the 3Cr13 coating. An XPS-based wear surface composition analysis and SEM wear scar topography results show that the FeNiCrAl coating produces not only Fe, Ni and Cr oxides but also Ni-Al intermetallic compounds during high-temperature friction. After the friction coefficient of the FeNiCrAl coating reaches its peak at 800 °C, more Al2O3 is formed around the Fe3Al, and these compounds aggregate to form a protective film that effectively prevents further intrusion of O ions. A dense oxide layer covers the wear surface, and the formation of hard-phase chemical compounds improves the wear resistance and bearing capability of the coating. Keywords: FeNiCrAl coating, High-speed electric arc spraying, Lamellar structure, Oxide, High-temperature friction

Abstract Background Blood-based gene expression or epigenetic biomarkers of Parkinson’s disease (PD) are highly desirable. However, accuracy and specificity need to be improved, and methods for the integration of gene expression with epigenetic data need to be developed in order to make this feasible. Methods Whole blood gene expression data and DNA methylation data were downloaded from Gene Expression Omnibus (GEO) database. A linear model was used to identify significantly differentially expressed genes (DEGs) and differentially methylated genes (DMGs) according to specific gene regions 5′—C—phosphate—G—3′ (CpGs) or all gene regions CpGs in PD. Gene set enrichment analysis was then applied to DEGs and DMGs. Subsequently, data integration analysis was performed to identify robust PD-associated blood biomarkers. Finally, the random forest algorithm and a leave-one-out cross validation method were performed to construct classifiers based on gene expression data integrated with methylation data. Results Eighty-five (85) significantly hypo-methylated and upregulated genes in PD patients compared to healthy controls were identified. The dominant hypo-methylated regions of these genes were significantly different. Some genes had a single dominant hypo-methylated region, while others had multiple dominant hypo-methylated regions. One gene expression classifier and two gene methylation classifiers based on all or dominant methylation-altered region CpGs were constructed. All have a good prediction power for PD. Conclusions Gene expression and methylation data integration analysis identified a blood-based 53-gene signature, which could be applied as a biomarker for PD.

Background: microRNAs have been reported to play critical roles in cancer and to have potential as diagnostic biomarkers. During miRNA biogenesis, one strand of the miRNA hairpin precursor is preferentially selected as a functionally mature miRNA, while the other strand is typically degraded. Arm switching occurs when the strand preference is changed. This preference can be different and can change dynamically depending upon the species, tissue types, or development stages. Due to recent advances in next-generation sequencing methods, arm switching has been observed in a variety of cancers. Methods: A tumour miRNA-Seq dataset was collected from The Cancer Genome Atlas (TCGA). The support vector machine (SVM) method combined with 5-fold cross validation was applied to select the best combination of arm-switched miRNA tumour markers. Survival analysis was also applied to identify patient survival associated miRNA markers. Findings: We observed 51 arm-switched miRNAs and of these, 7 were associated with patient survival. Twenty-three 1-combination arm switching miRNAs with excellent diagnostic value were identified. Interestingly, ovarian cancer showed a significant difference in arm switching pattern compared with 32 other cancers. Interpretation: These results suggest that arm switching miRNAs could be used as potential biomarkers for various cancers. Fund: This work was partially supported by the National Natural Science Foundation of China (no. 61472158, 61572227), and University of Macau Faculty of Health Sciences (MYRG2016-00101-FHS). Keywords: microRNA, Arm switching, Pan-cancer, Biomarker, SVM, Survival analysis

MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson’s disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic Caenorhabditis elegans (C. elegans) nematodes overexpressing pan-neuronally human α-synuclein wild-type (WT) (HASNWT OX) or mutant (HASNA53T OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASNA53T OX compared with WT. Genetic crosses of HASNA53T OX PD animal models with tdp-1 null mutants, the C. elegans ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes T28F4.5, C34F6.1, C05C10.3, camt-1, and F54D10.3 were predicted to be targeted by cel-miR-1018, cel-miR-355-5p (C34F6.1 and C05C10.3), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.

Achieving magnesium-rare earth alloys with excellent mechanical properties remains a challenging goal in the aerospace industry. The integrated extrusion and equal channel angular pressing were employed to refine grain and improve the mechanical properties of Mg-xNd-2.0Sm-0.4Zn-0.4Zr alloys. The effect of Nd element on microstructure and mechanical properties of the extruded and subsequently aged alloys were carried out by varying the amount of the Nd element from 0 wt.% to 2.5 wt.%. The optical microscopy results indicated that the grain size was remarkably refined by the addition of Nd element. The grain size decreased from 29.7 μm to 10.9 μm with increasing of the Nd element from 0 wt.% to 2.5 wt.%. The transmission electron microscopy results showed that the nano-scaled basal lamellar precipitates, prismatic lamellar precipitates and granular precipitates were formed in α-Mg matrix. The amount of the precipitates increased significantly by the addition of Nd. Moreover, the strength of the alloys significantly improved with Nd. Superior strength and considerable plasticity were obtained as the content of Nd element reached 2.0 wt.%, while the tensile strength of the Mg-2.0Nd-Sm-Zn-Zr alloy (315 ± 5 MPa) increased by 35.8% with respect to the Nd-free alloy (232 ± 3 MPa).

Residual stresses model comprehensively considers the three main sources of residual stress during the coating deposition process: quenching stress, thermal stress and phase transformation-induced stress. With the deposited layer temperature, coating thickness, number of deposited layers and relevant workpiece dimensions as the input, the model can easily calculate the final residual stress distribution in the coating. Moreover, the thermal–mechanical behavior during the coating deposition process was revealed through experimental and theoretical analysis of coatings. The results showed that the coating fabricated within the range of 65.2–122.5 °C have relatively low residual stresses, ensuring relatively high service reliability. Keywords: High-speed electric arc spraying, Residual stress, Coating, Crankshaft, Theoretical analysis