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Abstract Background At present, fat transplantation is widely used in the plastic surgery industry, but the long-term preservation rate of transplanted fat decreases because of complications such as oil cysts due to the inability in macrophages to metabolize absorption. In cell-assisted lipotransfer technology, adipose-derived stem cells (ASCs) can influence the inflammatory response of grafts through the immunoregulation in macrophages, and the lipid metabolism in macrophages plays an important role in this process. Therefore, we hypothesized ASCs could improve the retention rate of fat grafts by regulating the progress of lipid metabolism in macrophages. Methods We established fat transplantation and ASC-assisted fat transplantation model in C57BL/6 mice in vivo, and bone marrow-derived macrophages cocultured with apoptotic adipocytes were treated with or without ASCs in vitro. Graft retention, tissue structure, fibrosis, macrophage phenotype transformation, lipid deposition, mitochondrial morphology, oxygen consumption rate (OCR), fatty acid β-oxidation (FAO) level, and ATP production were assessed. Additionally, fat transplantation and ASC-assisted fat transplantation model was treated with etomoxir which inhibits mitochondrial FAO. Macrophages pretreated with etomoxir were co-cultured with apoptotic adipocytes and treated with or without ASCs. The method aboved was used for detection and verification. Results In vivo, ASC-assisted fat transplantation improved macrophage mitochondrial expression and FAO level, promoted the early transformation of M2 macrophages, reduced the long-term lipid deposition of macrophages, and improved the retention rate of fat grafts. In vitro, ASCs up-regulated the level of mitochondrial FAO, OCR and ATP production in macrophages, reduced lipid deposition of macrophages and promoted M2 macrophages polarization by paracine function. The ability of ASCs in group pretreated with etomoxir to reduce the foaming of macrophages, promote the transformation to M2 macrophages, and improve the retention rate of fat transplantation was weakened. Conclusions ASCs increased the retention rate of transplanted fat by upregulating mitochondrial FAO to promote M2 polaration in macrophages. In addition, ASCs up-regulate mitochondrial FAO by paracrine effect to reduce foam cells formation and promote M2 transformation in macrophages in vitro.

Accurate determination of the inverse kinematics for the drilling arm of a drilling and anchoring robot is crucial in achieving automatic support in coal mine roadways. Addressing issues such as poor accuracy, limited real-time performance, and susceptibility to local optima, this study presents a novel approach for solving the inverse kinematics problem of an unconventional mechanical arm by combining Monte Carlo random sampling method and Newton iteration method. Initially, a kinematics model is established based on the structure of the drilling arm, and individual coordinate systems are defined for each joint to enable forward kinematics solutions. The Monte Carlo method is employed to determine the motion space of the drill boom. By subdividing the motion space into smaller cubes with a defined step size, a mapping relationship is established between the spatial coordinates of these cubes and the corresponding joint variable values. Using the transformation matrix associated with a given target space point, an index function is employed to identify the relevant small cubes. The points within these cubes, which are closest to the target space point, are calculated, and their corresponding joint variable values are used as initial values. The Newton iteration method is then introduced, utilizing the iterative formula for multivariate functions to determine the variation of each joint variable. The inverse kinematics solution for the unconventional manipulator is obtained through iterative cycles. The simulation results show that, compared with Newton-Raphson iterative method based on random initial values and the particle swarm optimization algorithm, the corresponding average angle error of the calculation results of this method is reduced by 64.98% and 57.34%, and the average time consumption is reduced by 35.90% and 22.33%, respectively, thereby enhancing solution accuracy and real-time performance. The feasibility and effectiveness of the proposed Monte Carlo and Newton iteration method for solving the inverse kinematics problem in unconventional manipulators are verified. Overall, this research provides evidence supporting the practicality and efficiency of the proposed Monte Carlo random sampling method and Newton iteration method for accurate inverse kinematics solutions in unconventional manipulators.

Mitophagy, a selective form of autophagy, plays a crucial role in maintaining optimal mitochondrial populations, normal function, and intracellular homeostasis by monitoring and removing damaged or excess mitochondria. Furthermore, mitophagy promotes mitochondrial degradation via the lysosomal pathway, and not only eliminates damaged mitochondria but also regulates programmed cell death-associated genes, thus preventing cell death. The interaction between mitophagy and various forms of cell death has recently gained increasing attention in relation to the pathogenesis of clinical diseases, such as cancers and osteoarthritis, neurodegenerative, cardiovascular, and renal diseases. However, despite the abundant literature on this subject, there is a lack of understanding regarding the interaction between mitophagy and cell death. In this review, we discuss the main pathways of mitophagy, those related to cell death mechanisms (including apoptosis, ferroptosis, and pyroptosis), and the relationship between mitophagy and cell death uncovered in recent years. Our study offers potential directions for therapeutic intervention and disease diagnosis, and contributes to understanding the molecular mechanism of mitophagy.

Aiming at the problems of low intelligence of current tunneling equipment, difficulty in describing over-excavation, under-excavation and abnormal collision in tunneling process, and difficulty in adapting traditional automatic cutting and memory cutting technology to complex geological conditions, a digital twin-driven virtual teaching memory cutting control method for cantilever roadheader is proposed. By analyzing the research situation of digital twin technology in the field of intelligent coal mining, the overall scheme of memory cutting control system of cantilever roadheader driven by digital twin is designed, and the key technology of memory cutting of cantilever roadheader under complex working conditions is studied. Firstly, the characteristics of digital twin and virtual reality technology are fully utilized to study the virtual teaching strategy under complex working conditions. Based on the Unity3D platform, the virtual twin model of the working face and equipment with the same size of the corresponding entity, the kinematics model of the cutting unit and the virtual collision detection model are established. The virtual model movement is controlled through the intelligent interactive interface at the virtual end, and the teaching trajectory is designed and optimized according to the worker’s experience, so that it can be used as the target expected trajectory of trajectory tracking to make up for the excessive dependence on the worker’s experience caused by the traditional underground manual teaching due to the harsh working conditions. Secondly, in order to improve the quality of section forming, the control method of teaching trajectory tracking and reproduction in memory automatic cutting stage is studied. The dynamic model of cutting part is established by Lagrange method, and the tracking control accuracy of end effector to teaching trajectory is improved by combining iterative learning with sliding mode control. Finally, the simulation control platform of the memory cutting of the cantilever roadheader is built. Through the real-time data transmission and interaction between the virtual space and the physical space and between the modules, the three-dimensional visual simulation of the memory cutting virtual teaching and trajectory tracking control process is completed in the virtual space, and then the memory automatic cutting trajectory tracking control command is generated and sent to the end effector of the physical entity of the cantilever roadheader to drive it to carry out the section forming cutting according to the teaching trajectory. At the same time, the physical sensor collects the pose data of the cantilever roadheader fuselage and the cutting arm, and reversely drives the virtual model to move synchronously. The closed-loop control of robot virtual model and physical entity is realized. On this basis, the virtual and real synchronization of the system, the motion consistency between the virtual prototype and the physical prototype, and the trajectory tracking and reproduction control accuracy are verified. The experimental results show that the system data transmission delay is low, which can ensure the virtual and real consistency and synchronization, and the trajectory tracking control accuracy meets the actual use requirements. This method provides a new idea for memory cutting and intelligent control of tunneling equipment.

Abstract Abnormal alternative splicing (AS) caused by alterations in spliceosomal factors is implicated in cancers. Standard models posit that splice site selection is mainly determined by early spliceosomal U1 and U2 snRNPs. Whether and how other mid/late-acting spliceosome components such as USP39 modulate tumorigenic splice site choice remains largely elusive. We observed that hepatocyte-specific overexpression of USP39 promoted hepatocarcinogenesis and potently regulated splice site selection in transgenic mice. In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner. USP39 depletion deregulated hundreds of AS events, including the oncogenic splice-switching of KANK2. Mechanistically, we developed a novel RBP-motif enrichment analysis and found that USP39 modulated exon inclusion/exclusion by interacting with SRSF6/HNRNPC in both humans and mice. Our data represented a paradigm for the control of splice site selection by mid/late-acting spliceosome proteins and their interacting RBPs. USP39 and possibly other mid/late-acting spliceosome proteins may represent potential prognostic biomarkers and targets for cancer therapy.

Abstract Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic reprogramming of CSCs has emerged as a promising strategy for inducing the transition from malignancy to benignity. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is required for DNA methylation inheritance. Here, we investigated the role and mechanism of UHRF1 in regulating CSC properties and evaluated the impact of UHRF1 targeting on HCC. Hepatocyte-specific Uhrf1 knockout (Uhrf1 HKO ) strongly suppressed tumor initiation and CSC self-renewal in both diethylnitrosamine (DEN)/CCl4-induced and Myc-transgenic HCC mouse models. Ablation of UHRF1 in human HCC cell lines yielded consistent phenotypes. Integrated RNA-seq and whole genome bisulfite sequencing revealed widespread hypomethylation induced by UHRF1 silencing epigenetically reprogrammed cancer cells toward differentiation and tumor suppression. Mechanistically, UHRF1 deficiency upregulated CEBPA and subsequently inhibited GLI1 and Hedgehog signaling. Administration of hinokitiol, a potential UHRF1 inhibitor, significantly reduced tumor growth and CSC phenotypes in mice with Myc-driven HCC. Of pathophysiological significance, the expression levels of UHRF1, GLI1, and key axis proteins consistently increased in the livers of mice and patients with HCC. These findings highlight the regulatory mechanism of UHRF1 in liver CSCs and have important implications for the development of therapeutic strategies for HCC.

IntroductionFood allergies have a substantial impact on patient health, but their mechanisms are poorly understood, and strategies for diagnosing, preventing, and treating food allergies are not optimal. This study explored the levels of and relationship between IL-17A and IFN-γ in the saliva of children with food allergies, which will form the basis for further mechanistic discoveries as well as prevention and treatment measures for food allergies.MethodsA case–control study with 1:1 matching was designed. Based on the inclusion criteria, 20 case–control pairs were selected from patients at the Skin and Allergy Clinic and children of employees. IL-17A and IFN-γ levels in saliva were measured with a Luminex 200 instrument. A general linear model was used to analyze whether the salivary IL-17A and IFN-γ levels in the food allergy group differed from those in the control group.ResultsThe general linear model showed a significant main effect of group (allergy vs. healthy) on the levels of IL-17A and IFN-γ. The mean IL-17A level (0.97 ± 0.09 pg/ml) in the food allergy group was higher than that in the healthy group (0.69 ± 0.09 pg/ml). The mean IFN-γ level (3.0 ± 0.43 pg/ml) in the food allergy group was significantly higher than that in the healthy group (1.38 ± 0.43 pg/ml). IL-17A levels were significantly positively related to IFN-γ levels in children with food allergies (r=0.79) and in healthy children (r=0.98).DiscussionThe salivary IL-17A and IFN-γ levels in children with food allergies were higher than those in healthy children. This finding provides a basis for research on new methods of diagnosing food allergies and measuring the effectiveness of treatment.

Emulsion is of great concern in the process of crude oil production. In the later stages of heavy oil reservoir development, the crude oil produced on the surface exists in the form of emulsion, accompanied by sand production. Some sand particles are transported to the surface with the fluid. It is necessary to determine the mechanism by which the type and size of clay particles affect the performance of emulsions in order to aid in demulsification. Therefore, the effects of different clay particles and sizes on the shape and stability of the emulsion and stability was studied. The research results show that emulsion droplets with added montmorillonite contain more clay particles in their interior compared to droplets with added kaolin and illite systems. The diameter of the droplets in the montmorillonite system is larger and mostly ranges between 10–12 μm. The proportion of droplets with a diameter of 12–20 μm in the kaolin and illite systems is smaller than that in the montmorillonite system. When the same type of clay particles are added, with the increase in particle size, the late-stage water volume and viscosity of the montmorillonite system are the highest. The range of water volume is 6.38–7.3 mL, and the viscosity slightly increases within the range of .07–.66 mPa·s. When the clay particles are 8–10 μm, the viscosity increase of each system also gradually becomes smaller. The molecular dynamics simulation results show that the effects of adding clay particles on the root mean square displacement in different directions are z-axis > y-axis > x-axis. The addition of clay particles in the system has a lower crude oil migration speed compared to the blank system, ranging from .0001 to .0003 Å2 /ps. The addition of clay particles mainly affects the root mean square displacement of oil droplets in the vertical direction. Through this study, the effects of different clay particles on the emulsion of heavy oil have been preliminarily determined, providing guidance for the treatment of heavy oil emulsions. [ABSTRACT FROM AUTHOR]

Low temperatures stress is one of the important factors limiting rice yield, especially during rice anther development, and can cause pollen sterility and decrease grain yield. In our study, low-temperature stress decreased pollen viability and spikelet fertility by affecting the sugar, nitrogen and amino acid contents of anthers. We performed RNA-seq and ISO-seq experiments to study the genome-wide transcript expression profiles in low-temperature anthers. A total of 4,859 differentially expressed transcripts were detected between the low-temperature and control groups. Gene ontology enrichment analysis revealed significant terms related to cold tolerance. Hexokinase and glutamate decarboxylase participating in starch and sucrose metabolism may play important roles in the response to cold stress. Using weighted gene co-expression network analysis, nine hub transcripts were found that could improve cold tolerance throughout the meiosis period of rice: Os02t0219000-01 (interferon-related developmental regulator protein), Os01t0218350-00 (tetratricopeptide repeat-containing thioredoxin), Os08t0197700-00 (luminal-binding protein 5), Os11t0200000-01 (histone deacetylase 19), Os03t0758700-01 (WD40 repeat domain-containing protein), Os06t0220500-01 (7-deoxyloganetin glucosyltransferase), Pacbio.T01382 (sucrose synthase 1), Os01t0172400-01 (phospholipase D alpha 1), and Os01t0261200-01 (NAC domain-containing protein 74). In the PPI network, the protein minichromosome maintenance 4 (MCM4) may play an important role in DNA replication induced by cold stress.