Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL-12 and IL-18, and innate immune stimuli such as ligation of TLRs. The secretion of IL-18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL-18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL-18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38/PI3K/AKT pathway, and that the activatedNK cells mediate HSC death in a TRAIL-involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38/PI3K/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression

Methods of grinding power signal acquisition and dynamic power monitoring database establishment

The grinding power monitoring experimental platform was built with PPC−3 power sensor and NI 9203 acquisition card. An intelligent grinding process decision-making system driven by monitored power data was developed based on LabVIEW software to promote green, efficient and intelligent grinding. In order to overcome the problems of huge amount of bottom process monitoring data (i.e. grinding dynamic power signals collected online) of the decision-making system, mixture with noise and unclear typical characteristics, a method of feature extraction of grinding power signals and establishment of relational database is proposed. The type Ⅱ Chebyshev low-pass filter was used to filter and improve the signal-to-noise ratio of grinding power signals. The peak and the valley characteristic points of power signals were extracted and marked in time domain based on the peak and the valley searching method, and the head and the tail correction and interpolation correction were carried out to ensure the integrity and accuracy of grinding power data. At the same time, the working state of grinding process was marked based on binarization, and the dynamic flow data was converted into string and stored in the cells of relational database. The grinding test results of bearing steel show that the database establishment method can accurately extract the grinding power characteristics and transform 2090000 dynamic data points into 2×52998 cell data, the data volume is reduced to 5.07% of the source data, which significantly reduces the storage scale of data and speeds up the access speed of grinding database

Study on a Novel Strategy for High-Quality Grinding Surface Based on the Coefficient of Friction

Surface quality has a significant impact on the service life of machine parts. Grinding is often the last process to ensure surface quality and accuracy of material formation. In this study, a high-quality surface was developed by determining the coefficient of friction in grinding a quartz fiber-reinforced silica ceramic composite. By processing the physical signals in the grinding process, a multi-objective function was established by considering grinding parameters, i.e., surface roughness, coefficient of friction, active energy consumption, and effective grinding time. The weight vector coefficients of the sub-objective functions were optimized through a multi-objective evolutionary algorithm based on the decomposition (MOEA/D) algorithm. The genetic algorithm was used to optimize the process parameters of the multi-objective function, and the optimal range for the coefficient of friction was determined to be 0.197~0.216. The experimental results indicated that when the coefficient of friction tends to 0.197, the distribution distance of the microscopic data points on the surface profile is small and the distribution uniformity is good. When the coefficient of friction tends to 0.216, the surface profile shows a good periodic characteristic. The quality of a grinding surface depends on the uniformity and periodicity of the surface’s topography. The coefficient of friction explained the typical physical characteristics of high-quality grinding surfaces. The multi-objective optimization function was even more important for the subsequent high-quality machining of mechanical parts to provide guidance and reference significance

Low-Band-Gap Conjugated Polymers of Dithieno[2,3‑<i>b</i>:7,6‑<i>b</i>]carbazole and Diketopyrrolopyrrole: Effect of the Alkyl Side Chain on Photovoltaic Properties

Four donor–acceptor (D–A) conjugated polymers of dithieno­[2,3-<i>b</i>;7,6-<i>b</i>]­carbazole (DTC) and diketopyrrolopyrrole, which have different alkyls on the nitrogen atom in the DTC unit and are named as <b>P-C8C8</b>, <b>P-C5C5</b>, <b>P-C12</b>, and <b>P-C10</b>, respectively, have been synthesized for studying the effect of the alkyl side chains on the optoelectronic properties of the polymers. All polymers are soluble in various organic solvents and exhibit identical optical band gaps (<i>E</i>_g^opt) of ∼1.3 eV and highest occupied molecular orbital energy levels of ∼−5.1 eV. Organic thin-film transistors and bulk heterojunction polymer solar cells (BHJ PSCs) with phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM) as the electron-accepting material were fabricated via solution spin-casting. Compared to the polymers substituted by branched alkyl chains, the polymers with straight alkyl chains show higher hole mobility. Of these polymers, <b>P-C10</b> exhibits the highest field effect mobility up to 0.011 cm²/V·s. The alkyl chain on the DTC unit has a strong impact on the film morphology of polymer:PC₇₁BM blends. Severe phase separation was found for polymers containing branched alkyl chains, and those with straight alkyl chains formed uniform films featuring fine phase separation. An open-circuit voltage (<i>V</i>_oc) of 0.72 V, a short-circuit current density (<i>J</i>_sc) of 13.4 mA/cm², a fill factor (FF) of 62%, and a power conversion efficiency (PCE) of 5.9% were demonstrated for BHJ PSCs based on the <b>P-C10</b>:PC₇₁BM [1:3 (w/w)] blend film

Interface-Induced Crystalline Ordering and Favorable Morphology for Efficient Annealing-Free Poly(3-hexylthiophene): Fullerene Derivative Solar Cells

A simple approach to fabricate high-efficiency annealing-free poly­(3-hexylthiophene): [6,6]-phenyl C₆₁-butyric acid methyl ester (P3HT:PCBM) solar cells is reported by using p-type CuI to substitute PEDOT:PSS as anode buffer layer. It is found that the P3HT:PCBM blend films deposited on CuI surface show different orientation of crystalline P3HT domains and phase separation from those deposited on PEDOT:PSS surface. A nanoscale phase separation of P3HT and PCBM with domain sizes about 10–30 nm is formed for the P3HT:PCBM blend films deposited on CuI surface. Absorption and grazing incidence X-ray diffraction (GIXRD) experiments indicate that the CuI layer not only induces the self-organization of P3HT chains into well-ordered structure but also results in the vertical orientation of π–π stacking planes of P3HT with respect to the substrate which is favorable for the hole collection in polymer solar cells. Hole-transport investigation discloses that hole mobility of the as-spincast P3HT:PCBM blend film on CuI surface is increased with 3 orders of magnitude compared to the P3HT:PCBM film deposited on PEDOT:PSS. A power conversion efficiency of 3.1% for the as-spincast P3HT:PCBM solar cell with CuI buffer layer is about 4-fold enhancement compared to 0.83% of the control device with PEDOT:PSS, and is comparable to the reported P3HT:PCBM solar cells subjected to post thermal treatments. This work implies that interfacial engineering is a promising approach for manipulating morphology of active layer and can potentially simplify the process and shorten the fabrication time of polymer solar cells in low-cost roll-to-roll manufacturing

Face-On and Edge-On Orientation Transition and Self-Epitaxial Crystallization of All-Conjugated Diblock Copolymer

The orientation transition and self-epitaxial crystallization of all-conjugated diblock copolymers poly­(<i>p</i>-phenylene)-<i>block</i>-(3-hexylthiophene) (PPP-<i>b</i>-P3HT) were systematically investigated by <i>in situ</i> temperature-resolved two-dimensional grazing incidence X-ray diffraction (2D GIXD) in step-by-step heating and cooling process. B39T18 was selected; the results of 2D GIXD showed that the PPP block crystal adopted a face-on orientation while the crystallization of P3HT block was hindered in as-casted films. Three different molecular orientations transition were obtained in self-epitaxial crystallization circles. First, P3HT crystallize with edge-on during the heating process and induced the PPP blocks crystallized with edge-on during the cooling process. Then, the as-casted film was heated in the melting temperature region of PPP blocks and isothermally crystallized. The partial melting of PPP blocks promoted the P3HT blocks crystallize in a face-on due to the steric limitation effect; PPP blocks crystallized with a face-on via the self-epitaxy during cooling. Furthermore, the face-on transformed to thermodynamically stable edge-on in the melt annealing process

Printable Highly Conductive Conjugated Polymer Sensitized ZnO NCs as Cathode Interfacial Layer for Efficient Polymer Solar Cells

We report a facile way to produce printable highly conductive cathode interfacial layer (CIL) for efficient polymer solar cells (PSCs) by sensitizing ZnO nanocrystals (NCs) with a blue fluorescent conjugated polymer, poly­(9, 9-bis-(6′-diethoxylphosphorylhexyl) fluorene) (PFEP). Herein, PFEP plays dual distinctive roles in the composite. Firstly, PFEP chains can effectively block the aggregation of ZnO NCs, leading to uniform and smooth film during solution processing via assembly on ZnO NC surfaces through their pending phosphonate groups. Secondly, PFEP can greatly improve the conductivity of ZnO NCs by charge transfer doping, that is the charge transfer from the sensitizer driven by electron-chemical potential equilibrium, which could be even more pronounced under light illumination because of light excitation of PFEP sensitizer. The increased conductivity in ZnO-PFEP layer renders more efficient electron transport and extraction compared to pristine ZnO layer. This ZnO-PFEP CIL was successfully applied to PSCs based on three polymer donor systems with different band-gaps, and efficiency enhancements from 44 to 70% were observed compared to those PSCs with pristine ZnO CIL. The highest efficiency of 7.56% was achieved in P­(IID-DTC):PC₇₀BM-based PSCs by using ZnO-PFEP film as CIL. Moreover, the enhanced conductivity due to the charge-transfer doping effect allows thick ZnO-PFEP film to be used as CIL in high-performance PSCs. Both the high conductivity and good film-forming properties of ZnO-PFEP CIL are favorable for large-scale printable PSCs, which is also verified by high-efficiency PSCs with ZnO-PFEP CIL fabricated using doctor-blading, a large-scale processing technique. The work provides an efficient printable cathode interfacial material for efficient PSCs

High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

<div><h3>Background</h3><p>Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort.</p> <h3>Methodology/Principal Findings</h3><p>Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group.</p> <h3>Conclusions</h3><p>At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates.</p> </div

Phylogenetic tree constructed by the neighbor-joining method based on allele frequencies of HLA-A and HLA-B loci shows the relationships of our cohorts with other populations.

<p>Uyghur Cohort included our Uyghur HIV-1 positive and negative groups. Han Cohort included our Han HIV-1 positive and negative groups.</p