Persulfate-based advanced oxidation processes (PS-AOPs) have emerged as a highly promising approach for remediating organic-contaminated soil. However, the substantial cost associated with the large injection volume of persulfate and the potential ecological risks arising from sulfate accumulation in the post-remediated soil have hindered the widespread application of this technology. To address these challenges, this study proposed a novel and environmental-friendly approach based on the reversible regeneration of ammonium persulfate (APS) through electrochemical synthesis, with the aim of realizing cyclic utilization of APS. Through our in-depth investigation, we have scrutinized the performance and kinetic behaviors of Fe2+-APS in the remediation of organic-contaminated soil, utilizing NAP as the target. By identifying the decisive factors for electrochemical regeneration of APS, we have also unraveled the underlying mechanisms governing the electrochemical synthesis of APS. Experimental results demonstrate an impressive degradation rate of 76.39
In order to improve the transverse alignment accuracy of the control network in Chinese Spallation Neutron Source (CSNS) Linac, a 200-m stretched wire-based system was established in the tunnel. A wire position sensor based on bi-telecentric technology (tWPS) was specially designed to obtain the offset with respect to the stretched wire. A control network adjustment algorithm with additional wire constraints has been developed. The laser tracker measured station by station in a free station way, and measured the control network and the fiducials of the tWPS at the same time. The offset observation equation was combined with the angle observation equation and distance observation equation of the laser tracker for joint solution. As a result, the transverse accuracy of the control network was improved from 0.061 mm without wire constraint to 0.028 mm with wire constraint, which indicates that the addition of wire constraints can indeed effectively improve the transverse accuracy of the longitudinal control network.
The environmental pollution caused by antibiotics is becoming more and more serious. Outer membrane proteins (OMPs) play key roles in the resistance of bacteria to antibiotics. Transcriptomic profiles of Esherichia coli treated with different types of antibiotics revealed the pathways and response mechanisms of OMP-related genes up- or down-regulated following antibiotics treatment. Among all the 4497 genes, 73 OMPs were screened. In gentamicin- or ampicillin-treated groups, 51 or 23 genes were differentially expressed, respectively. The results of protein-protein interaction networks showed that ompA , chiP , phoE , and cusC were overlapped hub genes in both groups. Considering the scores of nodes calculated by cytoHubba, OmpA was the key one among the OMPs through the calculation of Cytoscape. Finally, the knockout and overexpression mutants and complementation strain of ompA were constructed. The results of drug resistance to 4 types of antibiotics analysis confirmed the role of ompA in the resistance of E. coli to antibiotics. This work provides direct evidence for the role of outer membrane proteins, especially OmpA, in drug resistance of E. coli to different types of antibiotics. The findings in this study can lead to new strategies for improving the effectiveness of antibiotics.
A previous study, based on human single-cell RNA sequencing data and cellular and mice models, has shown that HES1 and KLF6 are driver genes of skin aging, exerting geroprotective effects. To evaluate whether there are genetic and epigenetic risk factors linked to skin aging mediated by HES1 and KLF6 in the real world, we conducted a large-scale population cohort study in China comprising 3,375 participants. We used the validated skin aging score SCINEXATMto evaluate skin aging and collected data on genotype, DNA methylation, and lifestyle questionnaire. We then analyzed 332 SNPs and 368 CpGs located near HES1 and KLF6, or regulating their expression (eQTL and eQTM), to investigate their association with the skin aging phenotypes. We found 9 SNPs located 10-23kb downstream of HES1 can downregulate HES1 and alleviate solar elastosis, while 5 SNPs can decrease HES1 expression and increase the number of pigment spots on the cheek. Furthermore, cg10480300 and cg06048750 located on KLF6 are associated with skin aging traits, including solar elastosis and evenness of pigment spots on the forearm, as well as lifestyle factors such as BMI and food deficiency. Mediation analysis showed that cg06048750 mediates the association between BMI, food deficiency, and evenness of pigment spots on the forearm (indirect effect of -0.001 and 0.007 respectively, both P<0.05), while cg10480300 mediates the association between BMI and solar elastosis (indirect effect=-0.001, P<0.05). In summary, our findings shed light on the potential genetic and epigenetic regulatory role of HES1 and KLF6 in the manifestation of skin aging.
Objective: Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics. Methods: A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system. Results: In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis (P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS (P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old (OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 (OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow (OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation (OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion: Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.
Previous studies showed that life stress negatively impacts skin, but the relevant mechanism is poorly understood. Here, we recruited 60 stressed and 60 relaxed people (19-29 years old) to study how stress affects the skin. Each volunteer completed a 31-items life stress questionnaire, 24-items skin questionnaire, 14-items skin trait testing, and provided a sample of suction blister fluid for quantifying 36 skin cytokines, and roofs for DNA methylome and transcriptome analysis. We found that the stressed group had more severe skin dullness than the relaxed group (P=7.36×10-6). There was no significant difference in skin cytokines between the two groups, while the stressed group had an altered skin methylome and transcriptome profile. We detected 289 differentially methylated probes (DMPs) and 10 differential expression genes. Integration of methylation and expression data revealed 7 functional epigenetic modules (P<0.05), which were involved in the glutamatergic synapse, axon guidance pathway, etc. In line with previous studies on plasma/salivary, we found that life stress also affects the glutamatergic synapse in the skin. Interestingly, the expression level of SERPINA1 was significantly associated with a DMP (r=-0.29, p=0.004, in TSS1500 of SERPINA1), and with skin dullness (β=1.88, P=0.03). SERPINA1 reportedly influences the morning plasma/salivary cortisol, a life stress marker. This study provided important insight into the impact of life stress on skin, and shed light on the relevant molecular mechanism.
In this work, first principle calculation is applied to establish systematic ground state elastic property data of three typical cubic monocarbides (Titanium carbide (TiC), Vanadium carbide (VC) and Niobium carbide (NbC)). The bulk modulus, Young’s modulus, shear modulus, and Poisson’s ratio are determined from the Voigt-Reuss-Hill approximation method and compared with other published data. The micro-Vickers hardness is also predicted, the hardness data is compared to published data. The anisotropy in elastic properties of the carbides is studied through calculating the universal elastic anisotropic index; percent anisotropy in compressibility and shear as well as the shear anisotropic factors on the specific crystal planes. A python program is developed to integrate first principle calculation in Materials Studio data and establish the directional anisotropy in elastic properties in 3D space and projection on key crystal planes. 3D constructions and plane projection of the elastic properties based on the maximum, minimum and averaged values approaches is used to present and compare the anisotropy feature of the carbides. The data for E, G and Poisson’s ratio is comparatively analysed and discussed, and future direction in developing systematic data through physical modelling is discussed.
Background: Apart from the central role of activated JAK/STAT signaling pathway, ASXL1 mutations are the most recurrent additional mutations in myeloproliferative neoplasms (MPNs) and occurred much more common in myelofibrosis (MF) than essential thrombocythemia (ET) and polycythemia vera (PV) patients. However, the mechanism of the association with ASXL1 mutations and bone marrow (BM) fibrosis remains unknown. Aims: To investigate the role of ASXL1 mutations in MF acceleration and explore the underlying mechanism. Methods: We studied the clinical data of 302 consecutive MF patients in our hospital. For mouse model study, Vav1-Cre mice, Asxl1flox/flox and Jak2V617F/+ knockin alleles were used to achieve hematopoietic cell-specific Jak2V617F/+/Asxl1flox/flox (Asxl1-/-Jak2VF), Jak2V617F/+ (Jak2VF), and Asxl1flox/flox (Asxl1-/-) mice. Integrated analysis of RNAseq, transposase-accessible chromatin using sequencing (ATAC-Seq) and chromatin immunoprecipitation (ChIP)-seq were performed to explore the underlying mechanism. Results: 98 of 302 (32.5%) patients harbored ASXL1 mutations. ASXL1 mutations are correlated with higher monocyte counts, increasing CD34+ cells in peripheral blood (PB), larger spleen sizes, and higher MF grades. Consistent with clinical findings, Asxl1-/-Jak2VF mice showed lower platelet counts, higher monocyte counts and c-kit+ cells in PB compared with Jak2VF mice. Hematopoietic stem and progenitor cells (HSPCs) compartment analysis revealed increased granulocyte/macrophage progenitors (GMPs), and megakaryocyte /erythroid progenitors (MEPs) in spleens of Asxl1-/-Jak2VF, not in BM compared with Jak2V617F mice (Figure 1A), in line with increased spleen weights of Asxl1-/-Jak2VF mice (Figure 1B). Histology analysis revealed reticulin infiltration in BM of Asxl1-/-Jak2VF mice, not in other age-matched genotypes. Both ASXL1MT MF patients and Asxl1-/-Jak2VF mice showed increased monocytes/macrophages in BM (Figure 1C-D), accounting for more severe inflammation in ASXL1MT MF patients and mouse models. In vitro differentiation assay revealed monocyte/ macrophage differentiation bias of Asxl1-/-Jak2VF HSPCs (Figure 1E). In fibrosis driving cells analysis, ASXL1MT MF patients showed comparable mesenchymal stromal cells (MSCs) derived myofibroblasts while increased monocyte derived fibrocytes in BM compared with ASXL1WT MF patients (Figure 1F). In vitro fibrocyte differentiation assay (Figure 1G) and flow cytometry analysis confirmed increased fibrocytes in BM of Asxl1-/-Jak2VF mice compared with other genotypes. Mechanismly, Asxl1 deletion in Jak2VF HSPCs leads to enhancer activation of polycomb group (PcG) target genes, such as Egr1(Figure 1H). The upregulation of Egr1, which was validated in mouse models and patients (Figure 1I-J), in turn accounts for increased HSPCs commitment to monocyte/macrophage lineage (Figure 1K). Moreover, Egr1 induces the activation of Tnfa(Figure 1L) and thereby further drives the differentiation of monocytes to fibrocytes (Figure 1M). Accordingly, combined TNFR antagonist (R-7050) with ruxolitinib significantly reduces fibrocytes production in vitro in Asxl1-/-Jak2VF mice and ASXL1MT MF patients (Figure 1N-O). Image:Summary/Conclusion: Our study illustrated the crucial role of ASXL1 mutation in MPN phenotypes and BM fibrosis. ASXL1 mutations activate the EGR1-TNFA axis in MPNs, leading to monocyte/macrophage mediated inflammation and fibrocyte induced BM fibrosis. Ruxolitinib along with TNFR antagonist may ameliorate fibrocytes, providing an attractive theoretical approach for antifibrosis treatment.
The development of DNA nanotechnology make it possible to artificially generate complex nucleic acid nanostructures with controllable sizes and shapes. DNA origami emerges as an effective and versatile approach to construct two- and three-dimensional programmable nanostructures, and represents a milestone in the development of structural DNA nanotechnology. Due to its high degree of controllable geometry, spatial addressability, easy chemical modification and good biocompatibility, DNA origami has great potentials for applications in many fields. In this review, we briefly summarize the applications of DNA origami in antigen-antibody interaction, targeted drug delivery and the synthesis of biomaterials.
A multi-slit (MS) Very Small Angle Scattering (VSANS) instrument is now under construction on Beam Line 14 in China Spallation Neutron Source (CSNS). It is an upgrade of traditional SANS that extends the measurement length scale up to 1 micrometer. Success of the instrument depends on the precise alignment of the millimeter width MSs over more than 12 m. A prototype system has been built to rehearse the alignment of the 12 MSs. A traditional laser tracker is firstly chosen to align the 12 MSs coarsely to about ±100μm, which is less than the required accuracy of ±25μm. Then a laser-based non-contact alignment technique is used. When the expanded laser beam images MS directly to a high-resolution CCD, relative positions of each MS perpendicular to the beam line can be further aligned precisely. The transverse deviation of the 12 MSs can be kept within ±5μm. High accuracy of the technique guarantees the success of the VSANS instrument, and can be applicable to other systems that need high lateral precision over long distance.