Diverse potential of secretome from natural killer cells and monocyte-derived macrophages in activating stellate cells.

Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune cells from the circulation toward areas of inflammation. After infiltration, monocytes differentiate into monocyte-derived macrophages (MoMF) which are functionally distinct from resident KC. We herein aim to compare the in vitro signatures of polarized macrophages and activated hepatic stellate cells (HSC) with ex vivo-derived disease signatures from human NASH. Furthermore, to shed more light on HSC activation and liver fibrosis progression, we investigate the effects of the secretome from primary human monocytes, macrophages, and NK cells on HSC activation. Interleukin (IL)-4 and IL-13 treatment induced transforming growth factor beta 1 (TGF-ß1) secretion by macrophages. However, the supernatant transfer did not induce HSC activation. Interestingly, PMA-activated macrophages showed strong induction of the fibrosis response genes COL10A1 and CTGF, while the supernatant of IL-4/IL-13-treated monocytes induced the upregulation of COL3A1 in HSC. The supernatant of PMA-activated NK cells had the strongest effect on COL10A1 induction in HSC, while IL-15-stimulated NK cells reduced the expression of COL1A1 and CTGF. These data indicate that other factors, aside from the well-known cytokines and chemokines, might potentially be stronger contributors to the activation of HSCs and induction of a fibrotic response, indicating a more diverse and complex role of monocytes, macrophages, and NK cells in liver fibrosis progression.

A New Method of Predicting the Parameters of the Rotational Friction Welding Process Based on the Determination of the Frictional Heat Transfer in Ti Grade 2/AA 5005 Joints.

The article presents an original approach to determining the basic parameters of rotational friction welding (RFW) based on the analysis of friction heat transfer at the faying surfaces. Dissimilar Ti Grade 2/AA 5005 joints were used to demonstrate the method. The work established that for the analyzed joint, the optimum temperature at the faying surface that allow for a good quality weld to be obtained should be ~505 °C. On this basis, a map of optimal parameters was developed to achieve this temperature. This approach could potentially allow for more precise control of the welding process, leading to better joint quality and performance. The paper includes both a description of the technological process of friction welding and an attempt to explain the mechanism of the phenomena occurring in the welding area. The numerical calculations presented in the article were carried out using the ADINA System v. 9.8.2, which allows for the consideration of heat friction in the axial symmetric thermo-mechanical model. Frictional resistance was determined by the temperature-dependent friction coefficient. The assumed thermo-mechanical model required the determination of elastic-plastic properties versus temperature for the analyzed materials. The simulations of the friction welding were carried out for the different welding parameters and time. The different variants of friction welding were modelled.

Transcriptomic profiling of induced steatosis in human and mouse precision-cut liver slices.

There is a high need for predictive human ex vivo models for non-alcoholic fatty liver disease (NAFLD). About a decade ago, precision-cut liver slices (PCLSs) have been established as an ex vivo assay for humans and other organisms. In the present study, we use transcriptomics by RNASeq to profile a new human and mouse PCLSs based assay for steatosis in NAFLD. Steatosis as quantified by an increase of triglycerides after 48 h in culture, is induced by incremental supplementation of sugars (glucose and fructose), insulin, and fatty acids (palmitate, oleate). We mirrored the experimental design for human vs. mouse liver organ derived PCLSs and profiled each organ at eight different nutrient conditions after 24 h and 48 h time in culture. Thus, the provided data allows a comprehensive analysis of the donor, species, time, and nutrient factor specific regulation of gene expression in steatosis, despite the heterogeneity of the human tissue samples. Exemplified this is demonstrated by ranking homologous gene pairs by convergent or divergent expression pattern across nutrient conditions.

Tribological Aspects of Sheet Titanium Forming.

Friction, wear, and lubrication are inherent to all metal-forming processes. Unfortunately, they are particularly troublesome when forming titanium materials, which tend to form titanium buildup on the working surfaces of the forming tools. Lubrication is one of the most effective ways to separate contacting surfaces and eliminate galling, thus reducing tool wear. The paper presents the tribological aspects of titanium sheets forming using environmentally friendly lubricants with the addition of boric acid. The lubricant's effectiveness was assessed on the basis of technological tests, such as the strip drawing test, the Erichsen cupping test, and the formation of spherical drawn parts in industrial conditions. Moreover, the results of the numerical simulation of forming a titanium hat-shaped part are presented. Numerical calculations of forming processes were performed using the PamStamp 2G system based on the finite element method. Both experiments and numerical analyses showed the positive effect of lubricants with boric acid on sheet titanium forming.

Numerical and Experimental Analysis of Titanium Sheet Forming for Medical Instrument Parts.

The paper analyses the forming of the surgical instrument handles made of Grade 2 titanium sheets. Sheet metal forming is a technology ensuring high strength and light weight of products. Replacing stainless steels with titanium further reduces instrument weight and additionally provides the required resistance to corrosive environments typical for surgeries. The low instrument weight is important to prevent fatigue of surgeons and allow them to maintain high operational accuracy during long term surgeries. The numerical analysis of the technological process was performed in order to adapt it to forming tool handles using titanium sheets instead of steel sheets. The numerical calculations were experimentally verified. It was found that, in the case of titanium handles, it is necessary to use a blank holder in the first forming operation to eliminate sheet wrinkling in the flange area. The shape and dimensional accuracy of the drawn part after trimming were high enough and the 4th forming operation became unnecessary. Moreover, the process modification included lubrication using rapeseed oil with the addition of boric acid, which effectively prevents the galling of titanium on the working surfaces of the steel tools and ensures a more uniform distribution of plastic strains in the drawn part.

Evaluation of Usefulness of AlCrN Coatings for Increased Life of Tools Used in Friction Stir Welding (FSW) of Sheet Aluminum Alloy.

The study presents the results of examinations of wear in tools made of 1.2344 steel without and with an anti-wear coating in the process of welding overlap joints of sheet metal made of 7075-T6 aluminum alloy using friction stir welding (FSW) technology. A commercial anti-wear AlCrN coating (Balinit® Alcrona Pro by Oerlikon Balzers Coating Poland Sp. z o.o., Polkowice, Poland) was examined, applied using physical vapor deposition (PVD) and used to improve tool life in metalworking processes. Wear tests for the tools were conducted in industrial conditions at specific parameters of the friction stir welding process. Tool wear was evaluated through examination of the tool working surface. The results of the static tensile strength tests and metallographic examinations of the joints were used to evaluate the effect of tool wear and the coating impact on joint quality. The results obtained in the study show that the tool made of 1.2344 steel was intensively worn after the welding of a joint with the length of 200 m, increasing the risk associated with further use of the tool and suggesting the tool's low durability. The use of the AlCrN coating led to an increase in tool life. The coating limits the process of tool wear and can be used as an anti-wear coating for tools used in the FSW of aluminum alloys.

The Effect of Withdrawal Rate on Crystal Structure Perfection, Microstructure and Creep Resistance of Single Crystal Castings Made of CMSX-4 Nickel-Based Superalloy.

This study focuses on the evaluation of the crystal structure perfection in the single crystal made of CMSX-4 nickel superalloy and its effect on creep resistance. Single crystal castings were manufactured by directional solidification process at the withdrawal rate of 1, 3, 5 and 7 mm/min. Light (LM) and electron (SEM, TEM) microscopy, X-ray diffraction and Mossbauer spectroscopy were used for evaluation of the microstructure and crystal structure perfection. Castings were also subjected to creep tests. The best creep resistance was obtained for the casting manufactured at the withdrawal rate of 3 mm/min, characterized by the highest crystal structure perfection compared to the other castings examined.

Application of Inner Radiation Baffles in the Bridgman Process for Flattening the Temperature Profile and Controlling the Columnar Grain Structure of Directionally Solidified Ni-Based Superalloys.

The technique of flattening the temperature profile and controlling the formation of both the dendritic microstructure and grain structure in the directional solidification of nickel-based superalloy casting, using the novel inner radiation baffles (IRBs) in the Bridgman process, is presented in this paper. These baffles matched to the shape of mold and were placed horizontally along its height at various distances from the casting base. The plate castings of CMSX-4 superalloy were fabricated without and with the use of IRBs, withdrawing the mold at the rate of 6 mm/min from the heating to the cooling area of the industrial Bridgman furnace. Thermal analysis of the directional solidification of castings was carried out using the ProCAST software for a process where the various designs of the radiation baffle were applied. The results of the solidification conditions, the shape of liquidus and solidus isotherms, and grain structure obtained for the IRBs were compared with those reached for the standard ring-shaped (AERB) or perfectly adjusted (PARB) radiation baffles. The use of IRB resulted in flattening of the temperature distribution and decrease of the curvature of liquidus and solidus isotherms, as well as an increase of temperature gradient and cooling rate, compared with the process where AERB was only used. Consequently, primary dendrite arm spacing (PDAS) reached similar values across the width of casting and equaled to approximately 370 µm, reducing its average value by 26%, compared with the standard process. The change in predicted axial temperature gradient in casting was not found when thermophysical properties of molybdenum IRBs were used. The increase in graphite IRBs number in mold from seven to 14 caused the reduction of inhomogeneity of axial temperature gradient along the casting height.