Comprehensive analysis of juvenile idiopathic arthritis patients' immune characteristics based on bulk and single-cell sequencing data.

Background: The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients via bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed. Results: Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA. Conclusion: In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.

Comparative Study on Micro-Grinding Performance of 2.5D Cf/SiCs, 2.5D SiCf/SiCs, and SiC Ceramics.

To investigate the micro-grinding process and performance of 2.5D Cf/SiC composites and 2.5D SiCf/SiC composites in depth, single-factor micro-grinding experiments were conducted by using SiC ceramics as a comparison. Differences in the material removal process, surface microstructure, surface roughness, and grinding force of the three materials under the same grinding parameters were comparatively analyzed. The results indicate that crack propagation is severe during the micro-grinding process of SiC ceramics. The ground surface is uneven, accompanied by pit defects and large surface roughness Ra. However, the presence of reinforcing fibers and interfaces in the two types of composites can inhibit crack propagation or change their extension directions. Therefore, their surfaces are smooth and flat after grinding, with small defects and low surface roughness Ra. In addition, the grinding processes of the two composites are both related to fiber orientation. There are differences in crack propagation paths and fiber fracture positions in the weft fiber layer and the radial fiber layer, which result in different forms of grinding defects. During micro-grinding, the real-time force signals of 2.5D Cf/SiC composites and 2.5D SiCf/SiC composites are relatively stable, while the signals of SiC ceramics have a large number of spikes. The average micro-grinding force of the three materials is: SiC ceramics > 2.5D SiCf/SiC composites > 2.5D Cf/SiC composites.

Tool Wear Mechanism and Grinding Performance for Different Cooling-Lubrication Modes in Grinding of Nickel-Based Superalloys.

Tool wear introduced during grinding nickel-based superalloys was identified as a significant factor affecting the production quality of aero-engine industries concerning high service performance and high precision. Moreover, uncertainties derived from the various cooling-lubrication modes used in grinding operations complicated the assessment of grinding preformation. Therefore, this work investigated the tool wear mechanisms in grinding nickel-based superalloys that adopted five cooling-lubrication modes and investigated how the wear behaviors affected grinding performance. Results showed that chip-deposits covered some areas on the tool surface under dry grinding and accelerated the tool failure, which produced the highest values of tangential force, 7.46 N, and normal force, 14.1 N. Wedge-shape fractures induced by indentation fatigue were found to be the predominant wear mechanism when grinding nickel-based superalloys under flood cooling mode. The application of minimum quantity lubrication-palm oil (MQL-PO), MQL-multilayer graphene (MQL-MG), and MQL-Al2O3 nanoparticles (MQL-Al2O3) formed lubricity oil-film on the tool surface, which improved the capacity of lubrication in the tool-workpiece contact zone and provided 37%, 30%, and 52% higher coefficient of friction than dry mode, respectively. The results of this study demonstrate that lubricated oil-film produced by MQL modes reduces the possibility of fractures of cubic boron nitride (CBN) grits to some extent.

Impact of resampling interpolation FIR filter in the practical Kramers-Kronig receiver.

The practical Kramers-Kronig (KK) receiver has been a competitive receiving technique in the data-center, medium reach, and even long-haul metropolitan networks. Nevertheless, an extra digital resampling operation is required at both ends of the KK field reconstruction algorithm due to the spectrum broadening caused by adopting the nonlinear function. Generally, the digital resampling function can be implemented by using linear interpolation (LI-ITP), the Lagrange cubic interpolation (LC-ITP), the spline cubic interpolation (SC-ITP), time-domain anti-aliasing finite impulse response (FIR) filter method (TD-FRM) scheme, and fast Fourier transform (FFT)-based scheme. However, the performance and the computational complexity analysis of different resampling interpolation schemes in the KK receiver have not been thoroughly investigated yet. Different from the interpolation schemes of conventional coherent detection, the interpolation function of the KK system is followed by the nonlinear operation, which will broaden the spectrum significantly. Due to the frequency-domain transfer function of different interpolation schemes, the broadened spectrum will have a potential spectrum aliasing, which will cause serious inter-symbol interference (ISI) and further impair the KK phase retrieval performance. We experimentally investigate the performance of different interpolation schemes under different digital up-sampling rates (i.e. the computational complexity) as well as the cut-off frequency, the tap number of the anti-aliasing filter, and the shape factor of the TD-FRM scheme in a 112-Gbit/s SSB DD 16-QAM system over 1920-km Raman amplification (RFA)-based standard single-mode fiber (SSMF). The experimental results involve that the TD-FRM scheme outperforms other interpolation schemes and the complexity is reduced by at least 49.6%. In fiber transmission results, take 20% soft decision-forward error correction (SD-FEC) of 2×10-2 as the threshold, the LI-ITP and LC-ITP schemes only reach 720-km while others can reach up to 1440-km.

Effect of Initial Temperature on the Microstructure and Properties of Stellite-6/Inconel 718 Functional Gradient Materials Formed by Laser Metal Deposition.

Stelite-6/Inconel 718 functionally gradient materials (FGM) is a heat-resisting functional gradient material with excellent strength performance under ultra-high temperatures (650-1100 °C) and, thus, has potential application in aeronautic and aerospace engineering such as engine turbine blade. To investigate the effect of initial temperature on the microstructure and properties of laser metal deposition (LMD) functional gradient material (FGM), this paper uses the LMD technique to form Stelite-6/Inconel 718 FGM at two different initial temperatures: room temperature and preheating (300 °C). Analysis of the internal residual stress distribution, elemental distribution, microstructure, tensile properties, and microhardness of 100% Stelite-6 to 100% Inconel 718 FGM formed at different initial temperatures in a 10% gradient. The experimental results prove that the high initial temperature effectively improves the uneven distribution of internal residual stresses. Preheating slows down the solidification time of the melt pool and facilitates the escape of gases and the homogeneous diffusion of elements in the melt pool. In addition, preheating reduces the bonding area between the gradient layers, enhancing the metallurgical bonding properties between the layers and improving the tensile properties. Compared with Stellite-6/Inconel 718 FGM formed at room temperature, the mean yield strength, mean tensile strength, and mean elongation of Stellite-6/Inconel 718 FGM formed at 300 °C are increased by 65.1 Mpa, 97 MPa, and 5.2%. However, the high initial temperature will affect the hardness of the material. The average hardness of Stellite-6/Inconel 718 FGM formed at 300 °C is 26.9 HV (Vickers hardness) lower than that of Stellite-6/Inconel 718 FGM formed at 20 °C.

Analysis of Multigene Mutations in Lung Adenocarcinoma in Zunyi.

OBJECTIVE: Driver gene mutation in lung adenocarcinoma patients in Zunyi and its relationship with clinical features were probed in this investigation. METHODS: In total, with 244 patients with lung adenocarcinoma as study subjects, including 141 males and 103 females, amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was utilized for detecting multigene mutations. Subsequently, the relationship between gene mutation and clinical characteristics was analyzed. RESULTS: The total mutation rate of driver genes was 65.17%, including 48.36% EGFR, 6.15% KRAS, 5.74% ALK, 2.05% HER-2, 1.23% ROS1, 0.82% RET, 0.41% NRAS, and 0.41% BRAF. Among EGFR mutations, 47.46% were EGFR-19-deletion, 42.37% EGFR-21-L858R mutation, 4.24% EGFR-20-T790M mutation, 2.54% EGFR-21-L861Q mutation, 2.54% EGFR-20-insertion, and 0.85% EGFR-18-G719X mutation. Both female patients and nonsmoking patients with lung adenocarcinoma had a higher rate of EGFR mutation. Additionally, 15 patients with multiple mutations in EGFR, including 13 patients with 2 mutations in EGFR and 2 patients with 3 mutations in EGFR, were found. CONCLUSION: Among driver gene mutations in patients with lung adenocarcinoma in Zunyi, EGFR mutation has the highest incidence, followed by ALK fusion and KRAS mutation. Although both mutations and multisite mutations in the other driver genes account for a low proportion, they still have great clinical significance. Multigene mutation detection contributes to the rapid screening of patients with lung adenocarcinoma who respond to targeted therapy.

Effect of Laser Remelting on Cladding Layer of Inconel 718 Superalloy Formed by Laser Metal Deposition.

The brittle phase (Laves) of Inconel 718 parts formed by laser metal deposition (LMD) represents a bottleneck of the engineering applications. In order to investigate effectiveness of laser remelting (LR) technology on suppressing the formation of Laves phase, different laser scanning speeds of the LR process were adopted to build and remelt the single-pass cladding layers. The evolution of phase composition, microstructural morphology, and hardness of the LMD and LMD + LR specimens were analyzed. The experimental results show that different laser scanning speeds can obviously change the microstructural evolutions, Laves phase, and hardness. A low laser scanning speed (360 mm/min) made columnar dendrite uninterruptedly grow from the bottom to the top of the cladding layer. A high laser scanning speed (1320 mm/min) has a significant effect on refining Laves phase and reducing Nb segregation. When the laser scanning speed of LR process is equal to that of LMD, the cladding layers can be completely remelted and the content of Laves phase of the LMD + LR layer is 22.4% lower than that of the LMD layer. As the laser scanning speed increases from 360 to 1320 mm/min, the mean primary dendrite arm spacing (PDAS) values of the remelting area decrease from 6.35 to 3.28 µm gradually. In addition, the low content of Laves phase and porosity contribute to the growth of average hardness. However, the laser scanning speed has a little effect on the average hardness and the maximum average hardness difference of the LMD and LMD + LR layers is only 12.4 HV.

Experimental Investigation on Machinability of Aluminum Alloy during Dry Micro Cutting Process Using Helical Micro End Mills with Micro Textures.

Aluminum alloy material is widely used in the electronics, weapons, aviation and aerospace industries, due to its medium strength, good corrosion resistance, good toughness and excellent oxidation properties. With the trend of product miniaturization, micro cutting has become the mainstream technique for fabricating micro parts and components, so it is very meaningful and vital to work on removing the cutting fluid from the micro cutting process and make it totally sustainable and eco-friendly. In this work, an attempt has been made to fabricate micro textures onto the rear surface of helical micro end mills with diameters of less than 1 mm. Micro textures in the form of grooves were fabricated using a noncontact low speed wire electrical discharge turning technique. Dry micro cutting experiments were carried out on an aluminum alloy material using helical micro end mills with micro textures and the dry micro cutting surface quality and tool wear have been investigated. The influence of dry micro cutting parameters on the surface roughness parameters were also investigated. Experimental results showed that the Sa and Sq can be reduced to be about 1.56 µm and 2.08 µm, respectively. Contrasting results indicate that the implantation of micro textures does not deteriorate the dry micro cutting surface but improves the machined surface consistency of an aluminum alloy workpiece. The tool wear on helical micro end mills with micro textures involved in the dry micro cutting process of Al 6061 mainly include rear frictional wear, oxidation wear and diffusion wear.

Diabetes and multidrug-resistance gene mutation: tuberculosis in Zunyi, Southwest China.

BACKGROUND: The aim of this study was to clarify the characteristics of gene mutation related to multidrug-resistance (MDR) of tuberculosis (TB) and diabetes in Zunyi. METHODS: A total 763 patients with TB were screened for TB-DNA, TB-RNA, and acid-fast staining (all were positive). They were divided into the tuberculosis (TB) group and the diabetes mellitus-tuberculosis (DM-TB) group. We compared and analyzed the MDR gene rpoB, KatG, and inhA characteristics of gene mutations in the two groups by polymerase chain reaction (PCR)-reverse dot hybridization, and collected relevant clinical data to explore its correlation with the occurrence of multidrug resistance. RESULTS: Multidrug resistance occurred in 32 of the 525 patients in the TB group, and extensive drug resistance occurred in 15 of the 207 patients in the DM-TB group. In the DM-TB group, the mutation rates of ropBS531L and ropB531 (both 53.33%) were lower than those of the TB group (both 59.38%) in rifampicin resistance mutations. Most of the mutations were at the KatG315N site, conferring isoniazid resistance. CONCLUSIONS: The mutation sites of multidrug-resistant patients in Zunyi are mainly ropB531 and ropBS531L mutations, which are prone to co-occurrence; patients with MDR-TB alone are prone to mutations at the KatG315N site, while patients with diabetes and MDR-TB are more likely to have inhA15M site mutations.

Numerical and Experimental Analysis of Material Removal and Surface Defect Mechanism in Scratch Tests of High Volume Fraction SiCp/Al Composites.

This paper addresses a comprehensive and further insight into the sensitivity of material removal and the surface defect formation mechanism to scratch depth during single-grit scratch tests of 50 vol% SiCp/Al composites. The three-dimensional (3D) finite element model with more realistic 3D micro-structure, particle-matrix interfacial behaviors, particle-particle contact behaviors, particle-matrix contact behaviors and a Johnson-Holmquist-Beissel (JHB) model of SiC was developed. The scratch simulation conducted at scratch velocity 10 mm/min and loading rate 40 N/min revealed that the scratch depth plays a crucial role in material removal and the surface forming process. Brittle fracturing of SiC particles and surface defects become more deteriorative under a large scratch depth ranging from 0.0385 to 0.0764 µm. The above phenomenon can be attributed to the influence of scratch depth on SiC particles' transport; the increase in the amount of SiC particle transport resulting from an increase of scratch depth raises the occurrence of particle-particle collision which provides hard support and shock for the scratched particles; therefore, brittle fracturing gradually becomes the major removal mode of SiC particles as the scratch depth increases. On the deteriorative surface, various defects are observed; i.e., lateral cracks, interfacial debonding, cavies filled with residually broken particles, etc. The von Mises stress distribution shows that SiC particles bear vast majority of load, and thus present greater stress than the surrounding Al matrix. For example: their ratio of 3 to 30 under the scratch depth of 0.011 mm. Namely, SiC particles impede stress diffusion within the Al matrix. Finally, the SEM images of the scratched surface obtained from the single-grit scratch experiments verify the numerical analysis's results.

Tubeimoside I suppresses diabetes-induced bone loss in rats, osteoclast formation, and RANKL-induced nuclear factor-κB pathway.

Type 2 diabetes mellitus is often companied with osteoporosis, a process which involves osteoclast activation. In this study, we found tubeimoside I, a natural compound isolated from the Chinese medicinal herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), significantly ameliorated the decrease of bone mass in type 2 diabetes-induced osteoporosis in rats. It appears that tubeimoside I exerts this protecting effect through inhibiting osteoclast formation and function. Futhermore, our study showed that tubeimoside I inhibits NF-κB transcriptional activation and degradation of IκBα. Collectively, our results reveal that tubeimoside I attenuates osteoclastogenesis through down-regulating NF-κB signaling pathway, and is a potential candidate for the treatment of bone-destructive diseases like type 2 diabetic osteoporosis.

Analytical Investigation of the Micro Groove Surface Topography by Micro-Milling.

Micro-milling is an emerging processing technology for machining micro- and high-precision three dimensional parts that require the use of various materials (with sizes ranging from tens of micrometers to a few millimeters) in the field of advanced manufacturing. Therefore, it can be applied to manufacture the micro parts, but new challenges are raised about parts with high surface quality. Herein, both surface formation and micro machined surface roughness models are studied, with the aim of solving complicated problems regarding the quality of surface finish when micro-milling metallic materials. From a theoretical point of view, the first model for surface formation processes considering the strain gradient plasticity theory was built in the area around the cutting edge, and the minimum uncut chip thickness equation was derived. The model accounts for the properties of the work material in tertiary and quaternary zones on the minimum chip thickness. A second model for micro machined surface roughness based on the relationship of kinematics between cutting process and cutter edge was also developed, which takes the influences of tool run out into account. Both proposed models were introduced to analyze the tendency of surface roughness for micro grooves. Both models were also used to justify experimental results. The results show that the developed surface roughness model could be useful in predicting both roughness parameters and trends as a function of cutting parameters.