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C-plane sapphire (α-Al 2 O 3) is a commonly used substrate material for integrated circuits and Light-emitting diodes (LEDs). Efficient, stable, and low-damage lapping processes are used to ensure surface smoothness and meet application requirements. Fixed abrasive pads (FAPs) are typically used for the lapping of sapphire substrates, but the pads are prone to be glazed or even failed. In this study, loose alumina grains were used for in-situ reconditioning of fixed diamond abrasive pads. The material removal rate and surface roughness of the lapped sapphire substrate were calculated, the types and size distributions of the wear debris were analyzed, the surface morphology of the FAP after lapping was examined, and an online monitoring system was used to track the friction coefficient between the FAP and the sapphire substrate. In order to determine the ideal size and concentration of loose grains and to reveal the in-situ reconditioning mechanisms for the fixed diamond abrasive pads, the effects of the size and concentration of loose alumina grains in the lapping slurry on the in-situ reconditioning of the FAP were investigated. This was done by examining the wear behavior of loose alumina grains during the lapping processes of sapphire substrates. • In-situ reconditioning mechanism for fixed abrasive pads based on the wear behavior of loose grains is discussed. • Loose alumina abrasives improve lapping efficiency and stability of fixed diamond abrasive pads. • Three-body wear of alumina grains on the pad enhances self-conditioning ability of fixed diamond abrasive pads. • Size of loose alumina grains should be close to the maximum protrusion height of the diamond abrasives. [ABSTRACT FROM AUTHOR]

Due to its low thermal expansion coefficient and superior water/oxygen isolation properties, smooth 304 stainless steel may become the main substrate material for flexible organic light-emitting diode (FOLED) screens. However, in order to achieve a nano-scale smooth surface, 304 stainless steel substrates must undergo chemical mechanical polishing (CMP). A new type of polishing slurry consisting of hydrogen peroxide and ferric chloride was used to polish 304 stainless steel in our work. The material removal rate exceeds 700 nm/min and the surface roughness is below 5 nm after polishing using the optimized ratio of hydrogen peroxide and ferric chloride. Furthermore, the influence of the Fenton-like reaction between hydrogen peroxide and ferric chloride on chemical mechanical polishing 304 stainless steel is revealed by analyzing the concentration of Fe2+ ion and Fe element in the waste polishing slurry. A Fenton-like reaction occurs, including 2Fe3+ + Fe → 3Fe2+ and 2Fe2+ + H2O2 + 2H+ → 2Fe3+ + 2H2O, which enhances the polishing effect by metal-catalyzed oxidation. Hydrogen peroxide not only acts as an initiator of the Fenton reaction, but also as an inhibitor of the Fenton-like reaction, as it can react with hydroxyl radicals to generate peroxyl radicals. [ABSTRACT FROM AUTHOR]

Schizophrenia, as a stressful diagnosis, profoundly impacts the whole family, especially people with schizophrenia and their caregivers. This study tested the potential mediating role of expressed emotion in the association between mental health stigma and quality of life in caregiver‐patient dyads. Using a 2‐wave longitudinal design with a 6‐month interval between assessments, 161 dyads of patients with schizophrenia and their family caregivers (one patient and one caregiver) completed measures of mental health stigma, expressed emotion, and quality of life. The results showed that patients' self‐stigma had no significant actor or partner effect on expressed emotion or quality of life. In contrast, caregivers' stigmatizing attitudes toward patients had a significant partner effect on patients' perception of caregivers' expressed emotion and quality of life. The mediating effect of patients' perception of caregivers' expressed emotion in the association between caregivers' stigmatizing ideas toward patients and patients' quality of life was significant. By focusing on the interdependence of patients and their caregivers, this study highlights the role of caregivers' stigmatizing attitudes toward patients and patients' perception of caregivers' expressed emotion on patients' quality of life. Psychoeducation and interventions should not only aim to reduce the self‐stigma of people with schizophrenia but also their caregivers' stigmatizing ideas toward patients. Family interventions targeted at reducing the EE level of caregivers and patients' perception of caregivers' EE would also benefit the adaptation and quality of life of people with schizophrenia and their caregivers. [ABSTRACT FROM AUTHOR]

Signal‐amplified imaging of microRNAs (miRNAs) is a promising strategy at the single‐cell level because liquid biopsy fails to reflect real‐time dynamic miRNA levels. However, the internalization pathways for available conventional vectors predominantly involve endo‐lysosomes, showing nonideal cytoplasmic delivery efficiency. In this study, size‐controlled 9‐tile nanoarrays are designed and constructed by integrating catalytic hairpin assembly (CHA) with DNA tile self‐assembly technology to achieve caveolae‐mediated endocytosis for the amplified imaging of miRNAs in a complex intracellular environment. Compared with classical CHA, the 9‐tile nanoarrays possess high sensitivity and specificity for miRNAs, achieve excellent internalization efficiency by caveolar endocytosis, bypassing lysosomal traps, and exhibit more powerful signal‐amplified imaging of intracellular miRNAs. Because of their excellent safety, physiological stability, and highly efficient cytoplasmic delivery, the 9‐tile nanoarrays can realize real‐time amplified monitoring of miRNAs in various tumor and identical cells of different periods, and imaging effects are consistent with the actual expression levels of miRNAs, ultimately demonstrating their feasibility and capacity. This strategy provides a high‐potential delivery pathway for cell imaging and targeted delivery, simultaneously offering a meaningful reference for the application of DNA tile self‐assembly technology in relevant fundamental research and medical diagnostics. [ABSTRACT FROM AUTHOR]

Background and aims: Mucosal‐associated invariant T (MAIT) cells are innate‐like lymphocytes that display a critical role in various liver diseases. However, the role of MAIT cells in cholestatic liver fibrogenesis remains obscure. Our study aims to assess the contribution of MAIT cells and underlying mechanisms during this process. Methods: Cholestatic murine models using MAIT cell‐deficient (MR1−/−) and wild‐type (WT) mice were established by feeding a 0.1% 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐enriched diet or bile duct ligation (BDL). Liver samples were collected to determine the severity of fibrosis. Lymphocytes of the liver were isolated for analysing the phenotype and function of MAIT cells. Cell co‐culture experiments were performed to investigate the cross‐talk between MAIT and NK cells. Results: Liver MAIT cells were more activated with increased cytokines in cholestatic mice models than in control mice, although their frequency was decreased. MAIT cell deficiency led to severe liver inflammation and fibrosis with more activated HSCs in cholestatic mice. In addition, MR1−/− mice had an increased frequency of NK cells with higher expression of stimulatory receptors relative to WT mice. Paradoxically, activated MAIT cells significantly promoted the anti‐fibrotic ability of NK cells by enhancing their cytotoxicity against HSCs in co‐culture experiments. Importantly, this effect depended on direct cell–cell contact and TNF‐α produced by MAIT cells. Conclusion: Our findings indicate that MAIT cells ameliorate cholestatic liver fibrosis by enhancing the cytotoxicity of NK cells against HSCs. An in‐depth understanding of the MAIT cell‐mediated regulatory effect will provide more valuable immunotherapy strategies to treat liver fibrosis. [ABSTRACT FROM AUTHOR]

Multicomponent reactions provide a fast and efficient tool to construct various high-value molecules in the field of synthetic chemistry. Herein, we report a novel electrochemical oxidative four-component reaction for the synthesis of α-amino amides via C(sp3)–H bond activation. The active intermediate generated by the difunctionalization of isocyanide undergoes intermolecular rearrangement rather than the easier intramolecular rearrangement. This may be caused by a six-member ring transition state. In addition, under metal-free and external oxidant-free conditions, large-scale synthesis and good functional group tolerance indicated the potential applicability of this methodology. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that DAB2IP inhibits cancer progression, while HSP90AA1 promotes cancer progression. However, the specific regulatory mechanism of DAB2IP and HSP90AA1 in colorectal cancer (CRC) is not clear. Our aim is to investigate the role and mechanism of DAB2IP and HSP90AA1 in the development of CRC.Methods: We used bioinformation to analyze the interaction between DAB2IP and HSP90AA1 and predict their downstream pathways. Then, a series of in vitro and in vivo experiments were conducted to reveal the role of DAB2IP and HSP90AA1 in the invasion and metastasis of colorectal cancer, and flow cytometry was used to explore their effects on apoptosis.Results: Loss of DAB2IP was associated with poor prognosis of CRC. In contrast, elevated expression of HSP90AA1 was associated with the malignant behavior of CRC. The present study demonstrated a negative correlation between DAB2IP and HSP90AA1. Using bioinformatic analysis, we scanned SRP9 which was highly expressed in CRC, as a co-related gene of DAB2IP and HSP90AA1. Mechanistically, DAB2IP promoted apoptosis through HSP90AA1/SRP9/ASK1/JNK signaling axis in CRC.Conclusions: These findings provide evidence that DAB2IP-based therapy may enhance the anticancer effect of HSP90AA1 inhibitors, and combined targeting of DAB2IP and HSP90AA1 may be a powerful treatment strategy to combat CRC. [ABSTRACT FROM AUTHOR]

Telomerase is considered a biomarker for the early diagnosis and clinical treatment of cancer. The rapid and sensitive detection of telomerase activity is crucial to biological research, clinical diagnosis, and drug development. However, the main obstacles facing the current telomerase activity assay are the cumbersome and time-consuming procedure, the easy degradation of the telomerase RNA template and the need for additional proteases. Therefore, it is necessary to construct a new method for the detection of telomerase activity with easy steps, efficient reaction and strong anti-interference ability. Herein, an efficient, enzyme-free, economical, sensitive, fluorometric detection method for telomerase activity in one-step, named triggered-DNA (T-DNA) nanomachine, was created based on target-triggered DNAzyme-cleavage activity and catalytic molecular beacon (CMB). Telomerase served as a switch and extended few numbers of (TTAGGG) n repeat sequences to initiate the signal amplification in the T-DNA nanomachine, resulting in a strong fluorescent signal. The reaction was a one-step method with a shortened time of 1 h and a constant temperature of 37 °C, without the addition of any protease. It also sensitively distinguished telomerase activity in various cell lines. The T-DNA nanomachine offered a detection limit of 12 HeLa cells μL−1, 9 SK-Hep-1 cells μL−1 and 3 HuH-7 cells μL−1 with a linear correlation detection range of 0.39 × 102–6.25 × 102 HeLa cells μL−1 for telomerase activity. In conclusion, our study demonstrated that the triggered-DNA nanomachine fulfills the requirements for rapid detection of telomerase activity in one-step under isothermal and enzyme-free conditions with excellent specificity, and its simple and stable structure makes it ideal for complex systems. These findings indicated the application prospect of DNA nanomachines in clinical diagnostics and provided new insights into the field of DNA nanomachine-based bioanalysis. [Display omitted] • A DNA nanomachine for one-step highly efficient detection of telomerase activity. • Signal amplification requires transient not continuous participation of telomerase. • The reaction time was shortened to 1 h with enzyme-free at a constant temperature. • The LOD was 12 HeLa cells μL−1 with extensive detection range. [ABSTRACT FROM AUTHOR]

DNA nanotechnology, developing rapidly in recent years, has unprecedented superiorities in biological application-oriented research including high programmability, convenient functionalization, reconfigurable structure, and intrinsic biocompatibility. However, the susceptibility to nucleases in the physiological environment has been an obstacle to applying DNA nanostructures in biological science research. In this study, a new DNA self-assembly strategy, mediated by double-protonated small molecules instead of classical metal ions, is developed to enhance the nuclease resistance of DNA nanostructures while retaining their integrality and functionality, and the relative application has been launched in the detection of microRNAs (miRNAs). Faced with low-abundance miRNAs, we integrate hybrid chain reaction (HCR) with DNA self-assembly in the presence of double-protonated small molecules to construct a chemiluminescence detection platform with nuclease resistance, which utilizes the significant difference of molecular weight between DNA arrays and false-positive products to effectively separate of reaction products and remove the detection background. This strategy attaches importance to the nucleic acid stability during the assay process via improving nuclease resistance while rendering the detection results for miRNAs more authentic and reliable, opening our eyes to more possibilities for the multiple applications of customized DNA nanostructures in biology, including bioassay, bioimaging, drug delivery, and cell modulation. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent and inflammation-associated cancers. The tumor microenvironment (TME) plays an essential role in HCC development and metastasis, leading to poor prognosis. The overall TME immune cells infiltration characterizations mediated by immune-related genes (IRGs) remain unclear. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of HCC patients and TME cell infiltration characterization as well as responses to immunotherapy. Methods: We obtained differentially expressed immune-related genes (DE IRGs) between normal liver tissues and liver cancer tissues from The Cancer Genome Atlas (TCGA) database. To identify the prognostic genes and establish an immune risk signature, we performed univariable Cox regression survival analysis and the Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the DE IRGs by robust rank aggregation method. Cox regression analysis was used to identify independent prognostic factors in HCC. We estimated the immune cell infiltration in TME via CIBERSORT and immunotherapy response through TIDE algorithm. Results: We constructed an immune signature and validated its predictive capability. The immune signature included 7 differentially expressed IRGs: BIRC5, CACYBP, NR0B1, RAET1E, S100A8, SPINK5, and SPP1. The univariate and multivariate cox analysis showed that the 7-IRGs signature was a robust independent prognostic factor in the overall survival of HCC patients. The 7-IRG signature was associated with some clinical features, including gender, vascular invasion, histological grade, clinical stage, T stage. We also found that the 7-IRG signature could reflect the infiltration characterization of different immunocytes in the tumor microenvironment (TME) and had a good correlation with immune checkpoint molecules, revealing that the poor prognosis might be partly due to immunosuppressive TME. The Tumour Immune Dysfunction and Exclusion (TIDE) analysis data showed that the 7-IRG signature had great potential for indicating the immunotherapy response in HCC patients. The mutation analysis demonstrated a significant difference in the tumor mutation burden (TMB) between the high- and low-risk groups, partially explaining this signature's predictive value. Conclusion: In a word, we constructed and validated a novel, immune-related prognostic signature for HCC patients. This signature could effectively indicate HCC patients' survival and immunotherapy response. And it might act as potential immunotherapeutic targets for HCC patients. [ABSTRACT FROM AUTHOR]

This article details the design, implementation, and evaluation of mindful agency coaching and motivational interviewing interventions to develop undergraduate students' positive learning dispositions. A quasi-experimental design was employed in the study involving three groups: one control group, one intervention group of mindful agency coaching only (MA group), and another intervention group of mindful agency coaching plus motivational interviewing (MA+MI group). The main findings show that compared with the control group, the two intervention groups achieved significant improvements in mindful agency, self-efficacy, and emotional intelligence. However, there was no significant difference between the two intervention groups in posttests. Moreover, participants' improvement in mindful agency fully mediated the postintervention increases in self-efficacy, emotional intelligence, and metacognition. It can be concluded that mindful agency coaching and motivational interviewing are promising coaching approaches for undergraduate students to become mindful, resilient, and self-determined learners. [ABSTRACT FROM AUTHOR]

With proliferation of social media, image has become ubiquitous giving rise to the demand and importance of image semantic analysis and retrieval to access information quickly on social media. However, even with humongous information available, there are certain categories of images which are important for certain applications but are very scarce. Convolutional neural network is an effective method to extract high-level semantic features for image database retrieval. To overcome the problem of over-fitting when the number of training samples in dataset is limited, this paper proposes an image database retrieval algorithm based on the framework of transfer learning and feature fusion. Based on the fine-tuning of the pre-trained Convolutional Neural Network (CNN), the proposed algorithm first extracts the semantic features of the images. Principal Component Analysis (PCA) is then applied for dimension reduction and to reduce the computational complexity. Last, the semantic feature extracted from the CNN is fused with traditional low-level visual feature to improve the retrieval accuracy further. Experimental results demonstrated the effectiveness of the proposed method for image database retrieval. [ABSTRACT FROM AUTHOR]

• A concentrating solar collector system is applied to the actual production in a solar greenhouse. • Solar heat is delivered directly via a ground air pipe in the solar greenhouse. • Higher soil temperature rise is achieved owing to dual surface and ground heat sources. • A green, low-carbon, and pollution-free soil disinfection method is realized. Soil disinfection is a necessary step in solar greenhouses because of the soil borne diseases and pests caused by the continuous cultivation. However, the traditional physical soil disinfection methods lead to high energy consumption and high carbon emissions, chemical soil disinfection methods cause great soil pollution. Therefore, this study proposed a novel soil disinfection system that can avoid soil pollution and achieve solar-powered physical disinfection of planting soil. The proposed system collects solar energy with the trough compound parabolic concentrating solar collector system. The collected solar heat is continuously delivered by airflow to the heat exchange pipes buried in the soil. As a result, the soil temperature can be raised to the required level for a certain period to suppress the growth of weeds and kill pests and pathogenic bacteria. In this study, the variation trend of soil temperature in the actual greenhouse was measured in the field and compared with the calculation results. After 5 consecutive sunny days of continuous operation of the solar collector system, the maximum soil temperature on the surface, at the depth of 0.15 m and 0.3 m were 59 °C, 48.6 °C, and 43.4 °C, respectively. The duration of soil at a certain temperature can also reflect the disinfection effect, and the longest cumulative hours with the soil temperature at a depth of 0.15 m above 37 °C was 107.27 h. At the same time, the average microbial biomass carbon and the microbial biomass nitrogen decreased by 11.04 % and 8.56 %, respectively. Furthermore, the payback period of the system is 1.97 years and the greenhouse gas emissions can be reduced by about 410.82 kg CO 2 , 1.33 kg SO 2 , and 1.16 kg NO x every year. The research results indicate that this novel method of soil disinfection is feasible, which can improve soil temperature and achieve the purpose of soil disinfection. This study can provide a reference for green and low-carbon soil disinfection in solar greenhouses. [ABSTRACT FROM AUTHOR]

Currently, the problems of inefficient fixed abrasive lapping (FAL) for super hard and brittle material wafers (such as sapphire) with fixed abrasive pads (FAPs), restrict the development of the semiconductor industry. Most importantly, the mechanisms of FAL processes are still unclear, often analyzed based on the theoretical models of chemical mechanical polishing (CMP). However, the material removal models of CMP are specific to loose abrasives, do not effectively apply to the lapping processes for super hard and brittle material wafers with a FAP. In this paper, the spherical crown model modified by elastic-plastic mechanics and brittle-plastic transformation mechanism was applied to super hard and brittle material removal mechanism in FAL processes. In consideration of the influences of the yielding abrasives embedded in the FAP matrix and the matrix surface topography on the wafer-pad contact, a material removal model suitable for super hard and brittle material wafers lapped by FAPs was obtained. The loads applied on the fixed abrasives and the matrix asperities during the elastic-plastic-brittle deformation processes of wafers were analyzed, respectively. The model indicates that the back-off of the abrasives embedded in the FAP matrix intensifies along with the decrease of the matrix hardness and the increase of the abrasive size, respectively. The penetrating depth of the fixed abrasive can be raised by increasing matrix hardness, applied pressure, abrasive size, and decreasing abrasive number, as same as the elastic recovery of the super hard and brittle material slid by the abrasive after unloading. The pad matrix surface dressed by loose grains greatly affects the MRR of wafers. The predicted MRR of sapphire wafers based on the FAL model is consistent with experimental data. Finally, the keys to improving the processing efficiency of super hard and brittle material wafers are clarified in detail. [ABSTRACT FROM AUTHOR]

Hemorrhagic chronic radiation proctopathy (CRP) is a common complication after pelvic radiotherapy in patients with prostate or gynecological cancers. This systematic review was conducted to evaluate the efficacy and safety of argon plasma coagulation (APC) in treating hemorrhagic CRP. The databases of PubMed, Embase, and Cochrane Library were searched for related studies from inception to July 2017. Finally, 33 studies were identified with a total of 821 hemorrhagic CRP patients. After APC treatment, hemoglobin levels increased from 7.7–13.4 g/L to 11–14 g/L (including 15 studies). All (n=33) studies reported an effective rate in rectal bleeding, among which five studies had a rate of 100%. Short-term complications were reported in 31 studies, while long-term complications in 33 studies and no complication in 11 studies. As for the severe complications, perforation was reported by 2 out of 33 studies, and the incidences were 3.3% (1/30) and 3.7% (1/27), respectively. As for APC setting, argon gas flow rate (median 1.5 L/min) and electric power (median 50 W) had no significant influence on complications and hemostasis. In conclusion, current literature indicated that APC therapy was an effective and safe strategy for hemorrhagic CRP, and large-scale prospective studies are needed to warrant our study. [ABSTRACT FROM AUTHOR]

The localization of isothermal amplification systems has elicited extensive attention due to the enhanced reaction kinetics when detecting ultra-trace small-molecule nucleic acids. Therefore, the seek for an appropriate localization cargo of spatially confined reactions is urgent. Herein, we have developed a novel approach to localize the catalytic hairpin assembly (CHA) system into the DNA tile self-assembly nanostructure. Thanks to the precise programming and robust probe loading capacity, this strategy achieved a 2.3 × 105-fold higher local reaction concentration than a classical CHA system with enhanced reaction kinetics in theory. From the experimental results, this strategy could reach the reaction plateau faster and get access to a magnified effect of 1.57–6.99 times higher in the linear range of microRNA (miRNA) than the simple CHA system. Meanwhile, this strategy satisfied the demand for the one-step detection of miRNA in cell lysates at room temperature with good sensitivity and specificity. These features indicated its excellent potential for ultra-trace molecule detection in clinical diagnosis and provided new insights into the field of bioassays based on DNA tile self-assembly nanotechnology. [ABSTRACT FROM AUTHOR]

We propose a universal fluorescence method for detection of nucleic acids based on rolling circle amplification (RCA) combined with a magnetic DNA machine and using dengue virus nucleic acids as an example target. RCA specifically amplifies the target and yields a large number of initiators employing heat-labile double-stranded DNase. The magnetic DNA machine produces a fluorescence signal and eliminates background noise. This method achieved a wide linear range, promising recovery and ultrahigh recognition specificity for one-base mismatches, and indicates the potential application of this sensing strategy in the clinical diagnosis of nucleic acids of pathogens. [ABSTRACT FROM AUTHOR]

High-temperature vulcanized silicone rubber (HTV-SR) employed for composite insulators is continuously subjected to a complex environment of alternating heat, corona discharge, humidity, etc. These stresses (especially alternating heat) complicate the aging mechanism of HTV-SR, which lacks systematic investigation. In this paper, a multi-factor aging platform considering temperature cycling, moisture, and corona discharge is established. Specifically, four temperature-cycling settings are employed, each of which lasts for 15 cycles. The surface morphology, hydrophobicity, and chemical, mechanical, and electrical properties of aged samples are methodically characterized. Experimental results show that the aging degree is correlated to the range of temperature cycling, which is attributed to diverse crosslink-degradation degrees with different temperature differences. Under a large temperature difference (70 °C), HTV-SR possesses a high crosslinking degree and a low degradation degree, making the material hard but easy to crack with alternating thermal stress. Then, severe defects and water condensation emerge on the HTV-SR surface, which promote the diffusion of corona products and water molecules into the material. The subsequent rise in crosslinking density caused by in-depth oxidation further exacerbates the aging of the material. Consequently, it brings about poor hydrophobicity, high interfacial polarization, and shallow trap energy levels in HTV-SR. This work provides a detailed analysis of the aging mechanism of HTV-SR in a simulated on-site environment. [ABSTRACT FROM AUTHOR]

Anti-attrition and water lubrication are two areas where ceramics are widely applied. In comparison to pure ceramics, glass-ceramic composite materials are more accessible to machine and manufacture into water lubrication kits. However, current water lubrication theories are mainly applied to ceramic materials such as SiC, Si 3 N 4 , Al 2 O 3 and ZrO 2. Glass-ceramic water lubrication mechanisms are not involved, in particular, the specific development process of low friction glass-ceramics in the water environment is yet unknown, which limits the application of glass-ceramics. As a result, we developed custom-made γ-LiAlSi 2 O 6 glass-ceramics for a ball and a wafer that were utilized to conduct friction and wear tests. By contrasting the dry and wet friction coefficients between the ball and the wafer, abrasion losses and surface roughnesses of glass-ceramics, particle size distribution and zeta potential of wear debris over time, the water lubrication mechanisms of glass-ceramics in three different friction stages were clarified, the interactive lubrication effects of the electrical double layer and the dynamic fluid pressure ensure that the wet friction coefficient of the glass-ceramics is constant below 0.02. [Display omitted] • Water lubrication of a custom-made γ-LiAlSi 2 O 6 is first proposed and detailedly clarify via friction and wear tests. • Mechanical wear and tribochemical reaction of γ-LiAlSi 2 O 6 impel a rapid decrease of wet friction coefficient. • Electrical double layer and dynamic fluid pressure ensure the constant low friction coefficient in water lubrication. • Electrical double layer, dynamic fluid pressure, surface-bound hydration layer dominate water lubrication. [ABSTRACT FROM AUTHOR]

Tumor–stroma interactions are referred to as essential events in tumor progression. There has been growing attention that bone marrow-derived mesenchymal stem cells (BMSCs) can travel to tumor stroma, where they differentiate into tumor-associated fibroblast (TAF)-like cells, a predominant tumor-promoting stromal cell. However, little is definitively known about the contributors for this transition. Here, using an in vitro direct co-culture model of colon cancer cells and BMSCs, we identify that colon cancer cells can induce adjoining BMSCs to exhibit the typical characteristic of TAFs, with increased expression of α-smooth muscle actin (α-SMA). Importantly, the present data also reveals that activated Notch signaling mediates transformation of BMSCs to TAFs through the downstream TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Highlights: [•] GRP78 is detected in secretions of two colon cancer cell lines. [•] Secreted GRP78 facilitates differentiation of BMSCs to CAFs. [•] GRP78 induce BMSCs–CAFs transition through activating TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: During analysis of certain stability batches of an animal health product, an unknown peak was found at a level above the identification thresholds set by VICH. This unknown species is extremely labile in the gas phase under normal electrospray ionization (ESI) mass spectrometric condition. Multiple ions were detected with no clear indication of which one is the molecular ion. To overcome this challenge, we utilized tandem MS/MS analysis and multiple MS instruments. The slightly different ionization processes between the two different instruments provided strong, complementary evidence leading to the identification of the correct molecular ion. Based on the formula thus determined, the unknown species was found to be related to sesame oil, which is one of the major excipients used in this drug product. The unknown species was eventually identified as asarinin using high resolution LC–MS n in conjunction with mechanism-based stress studies, in which the unknown species was generated based on the degradation chemistry of sesamin as revealed by the LC–MS n analysis. This overall approach in combining LC–MS n analysis along with mechanism-based stress studies can be used as a general strategy for identification of unknown pharmaceutical impurities, especially the degradants related to the active pharmaceutical ingredient (API) and excipients. [Copyright &y& Elsevier]

Chemical mass shifts of nitro-aromatic compounds were measured in a custom-modified GCQ ion trap instrument. The average normalized chemical mass shift of 0.91 (Δm/m, %) for the molecular ions of 24 nitro-aromatic compounds examined is much larger than the average value of 0.41 (Δm/m, %) measured for a group of aromatic compounds without the nitro substituent. The larger chemical mass shifts associated with the nitro group could serve as a diagnostic for identifying this class of compounds in mixtures and a simple method of implementing this test is described. Samples were examined at two different ac resonance ejection frequencies, one corresponding to the non-linear resonance frequency at qz=0.80 where chemical mass shifts are small for all compounds, the other corresponding to qz=0.75 where chemical mass shifts are in full operation. The difference in apparent mass under these two conditions is used as an easily measured criterion for recognizing compounds that satisfy the mass shift criterion for nitro-aromatic compounds. [Copyright &y& Elsevier]

Relationships between chemical mass shifts and physiochemical properties of ions are sought by examining substituted acetophenones, benzophenones, and pyridines in a modified ion trap mass spectrometer. Systematic changes in chemical mass shift occur with changes in substituent in the acetophenones and the benzophenones. Brown’s σ+ constant, which is a measure of electronic effects of substituents in reactions that involve positive charge development, is shown to correlate linearly with chemical mass shifts in para-substituted acetophenones and benzophenones. Brown’s σ+ constant also correlates with the ease of dissociation of the ions via a correlation with ionization energy. It is suggested that ease of dissociation is the underlying factor in determining chemical mass shifts. The experimental results also suggest that dissociative collisions between ions and buffer gas make a much greater contribution to chemical mass shifts than do elastic collisions. [Copyright &y& Elsevier]

Continuous and long‐term use of traditional and new pesticides can result in cross‐resistance among pest populations in different fields. Study on the mechanism of cross‐resistance and related genes will help resistance management and field pest control. In this study, the pesticide‐resistance mechanism in Spodoptera frugiperda (FAW) was studied with field populations in 3 locations of South China. Field FAW populations were highly resistant to traditional insecticides, chlorpyrifos (organophosphate) and deltamethrin (pyrethroid), and had higher levels of cytochrome P450 activity than a non‐resistant laboratory strain. Inhibition of P450 activity by piperonyl butoxide significantly increased the sensitivity of resistant FAW in 3 locations to chlorpyrifos, deltamethrin and chlorantraniliprole (amide), a new type of insecticide, suggesting that P450 detoxification is a critical factor for insecticide resistance in field FAW populations. Transcriptomic analysis indicated that 18 P450 genes were upregulated in the field FAW populations collected in 3 regions and in 2 consecutive years, with CYP6a13, the most significantly upregulated one. Knockdown of CYP6a13 messenger RNA by RNA interference resulted in an increased sensitivity to the 3 tested insecticides in the field FAW. Enzyme activity and molecular docking analyses indicated that CYP6a13 enzyme was able to metabolize the 3 tested insecticides and interact with 8 other types of insecticides, confirming that CYP6a13 is a key cross‐resistance gene with a wide range of substrates in the field FAW populations across the different regions and can be used as a biomarker and target for management of FAW insecticide resistance in fields. [ABSTRACT FROM AUTHOR]

[Display omitted] • Particle-in-oil-in-water multiple emulsion adjuvant is a promising vaccine adjuvant. • The adjuvant with chitosan nanoparticles as the internal water phase had good cellular and humoral immune effects. • The increase in the content of the internal aqueous phase helps to reduce antigen concentration and reduce the cost of antigen purification. Particle-in-oil-in-water (P/O/W) multiple emulsion adjuvants introduce particles into the internal water phase of a water-in-oil-in-water emulsion, combining the advantages of both particle and emulsion adjuvants to enhance humoral and cellular immune responses. In this study, we optimized P/O/W multiple emulsion adjuvants. Chitosan, poly (lactic-co-glycolic acid), and aluminum gel were used to prepare the particles, which were introduced into a water-in-oil-in-water emulsion to obtain three P/O/W multiple emulsion adjuvants. The immune enhancement effects and safety of the three adjuvants were compared, and it was proven that the adjuvant with chitosan nanoparticles in the internal water phase had good cellular and humoral immune effects. Simultaneously, the proportion of the internal water phase increased from 13% to 20%, reducing the antigen concentration required for embedding to one-third of the original concentration and expanding the application range of the composite adjuvant. [ABSTRACT FROM AUTHOR]

With the popularization of autonomous vehicle (AV) technology, mixed traffic flows that consist of AVs and human-driven vehicles (HDVs) will appear in the real world. Although many studies of the features of mixed traffic flow have been carefully evaluated, few studies have focused on the effect of aggressive driving performance on mixed traffic flow. This study aims to develop an approach to evaluate the effects of aggressive driving on the stability and capacity performance under the conditions of AV and HDV mixed traffic flow. First, since a car-following model can describe the relationship between vehicles, we calibrate a car-following model for aggressive driving and nonaggressive driving behaviors based on real traffic data and previous research results. Then, in a mixed traffic flow environment, a basic linear stability formula and capacity calculation expression are developed that consider the effects of vehicle order on the capacity. Finally, because the proportion of aggressive driving and aggressive driving parameters may change, nine combinations of three aggressive driving proportions and three driving parameter cases are used for the sensitivity analysis. The results indicate that the effect of aggressive driving on mixed traffic flow is complex. When the proportion of aggressive driving is less than 35%, the increase in the proportion of aggressive driving increases the traffic capacity and reduces the unstable part. However, when the proportion of aggressive driving is greater than 35%, the increase in the proportion of aggressive driving increases the unstable part. When the penetration rate of AVs exceeds 0.490, mixed traffic flow remains stable at all aggressive driving proportions. In addition, the capacity of a mixed traffic flow may be improved as the penetration rate of AVs increases. To a certain extent, these conclusions provide a theoretical basis for formulating different management modes of AVs and HDVs. [ABSTRACT FROM AUTHOR]

Background: Immune cells and stromal cells in the tumor microenvironment play a vital role in the progression of colorectal cancer (CRC). The study aimed to screen valuable prognostic biomarkers in CRC based on stromal and immune scores. Method: The ESTIMATE algorithm was used to calculate the immune and stromal scores of CRC samples in TCGA. Then samples were divided into high and low score groups based on the median value of the scores. Differentially expressed genes (DEGs) associated with immune and stromal scores were screened. WGCNA and univariate COX regression analysis were performed to further identify key prognostic genes. Analysis of scRNA-seq for CRC was used for verifying the main source of the key genes. The prognostic value of they was validated based on The Gene Expression Profiling Interactive Analysis and GSE17536 dataset. TIMER and CIBERSORT algorithms were applied to analyze the correlations among key genes and tumor-infiltrating immune cells. Several pairs of colon cancer tissue were used to be proven. Result: 1314 upregulated and 4 downregulated genes were identified, which were significantly enriched in immune-related biological processes and pathways. Among these DEGs, SPOCK1 and POSTN were identified as key prognostic genes and mainly expressed in cancer-associated fibroblasts for CRC. High expression of SPCOK1 and POSTN was associated with advanced clinical stage, T stage, N stage, and poor prognosis of CRC. The results from CIBERSORT and TIMER revealed that SPOCK1 and POSTN were associated with tumor-infiltrating immune cells, especially macrophages and neutrophils. Meanwhile, in several pairs of human colorectal tissue samples, SPOK1 and POSTN were found to be significantly overexpressed in colorectal tissue compared with para-cancer tissue, and macrophage surface markers CD68 (co-expressed by M1 and M2 macrophages) and CD206 (M2-specific macrophage expression) were also overexpressed in cancer tissue. Besides, SPOCK1 and POSTN expression were positively correlated with the expression of immune checkpoints. Conclusion: Collectively, our results indicate that SPOCK1 and POSTN associated with CAF may be novel prognostic biomarkers in CRC and correlate with immune infiltrates. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Enteritidis (S. Enteritidis) can colonize in the intestinal tract of chickens and transmit to humans. In order to decrypt the mechanism of avian resistance to S. Enteritidis, we utilized two China local chicken breeds to generate the reciprocal crosses (the Cross and the Reverse‐cross). The two lines of hybrids were orally inoculated with S. Enteritidis at 2‐day old and sampled at 3 days post‐inoculation. Along the analysis direction of multi‐omics, differential metabolites, functional pathways and correlated microbes, we found that 12 species of microbes thrived upon S. Enteritidis challenge and probably contributed to the intestinal stability in the Cross by enhancing the production of phenylpropanoids. Our findings can help to understand the symbiotic and resistant mechanisms derived from the intestinal microbiota. [ABSTRACT FROM AUTHOR]

In online influence maximization, a learner aims to find a specified number of nodes that have the greatest influence in a network, by iteratively selecting seed nodes (i.e., initially activated nodes) and updating its knowledge of the network via activation feedback. Existing approaches to this problem customarily assume that the structure of the network is known in advance, and focus on how to utilize activation feedback to reveal the features of seed nodes in each iteration, regardless of non-seed nodes which occupy the majority of the node set. In this paper, we present a novel learning framework to carry out online influence maximization in the absence of network structure. In our framework, the underlying influence relationships between nodes are inferred based on activation feedback, and then the influence reachabilities of both seed nodes and non-seed nodes are updated with the latest inferred influence relationships, so that more knowledge about the network can be used to guide the selection of seed nodes in the next iteration. Extensive experiments on both synthetic and real-world networks are conducted, and the results verify the efficacy of our proposed framework. [ABSTRACT FROM AUTHOR]

In China, bereaved parents who have lost their only child are known as Shidu parents, and they tend to present high levels of prolonged grief reactions. To date, a widespread focus has been placed on positive social support, while potential negative experiences have been relatively neglected. Additionally, the role of social support from different sources (i.e. close family members [partner, siblings, grandchildren], peers, and others [relatives, friends, colleagues]) has not been examined thoroughly. The present study investigated whether social support from different sources has a differential impact on postloss adaptation (i.e. prolonged grief and growth). The loss-orientated and restoration-orientated coping strategies of the dual process model were also tested for their mediating roles. A total of 277 Chinese Shidu parents were recruited to complete a series of questionnaires including social support from different sources, prolonged grief symptoms, posttraumatic growth, and dual process coping strategies. Correlation analyses, paired sample t tests and structural equation modelling were conducted. More positive support were related to less prolonged grief symptoms and more posttraumatic growth, while more negative support was only related to more prolonged grief. Positive support from close family members and others was significantly related to prolonged grief/growth, and negative support from these sources was significantly positively associated with prolonged grief. Positive or negative support from people who shared a similar experience was unrelated to prolonged grief/growth. Positive and negative support were related to prolonged grief and growth through loss-oriented coping strategies. Overall, the present study indicated that positive and negative support experiences from different sources functioned differently in the recovery of Chinese Shidu parents and that loss-oriented coping played a mediating role. These findings highlight the importance of differentiating social support by traits in coping with grief and the crucial mediating role of loss-oriented coping. More positive support correlated with less prolonged grief and more growth, while more negative support correlated with more prolonged grief. Support from family members and friends was more potent than that from peers. Social Support correlated with prolonged grief/growth through loss-oriented coping. [ABSTRACT FROM AUTHOR]

Citrobacter freundii , a common pathogen of freshwater fish, severely restricts the sustainable development of the aquaculture industry. In this study, the novel C. freundii strain CFC202 was isolated from the intestines of crucian carp, which was annotated with three virulence factors related to promoting bacterial colonization and causing anemia by the whole genome analysis. We found that the strain adhered to the surface of hepatic L8824 cells, and actin aggregation occurred at the adhesion site of the strain. Then, C. freundii was fluorescently labelled and imaged the distribution of crucian carp under an In Vivo Imaging System (IVIS) during natural infection. The results showed that this strain mainly gathered in the intestines of crucian carp, and the intestinal villi were severely damaged by TEM. From the results of histopathological examination, the intestinal mucosa was obviously shed and various organs were damaged. Hence, we speculated that C. freundii could cause attaching and effacing (A/E) lesions to fish cells, which in turn caused pathological changes to various organs. Moreover, we constructed C. freundii ghost (CFG) and evaluated their immune effects by oral and injection immunization in crucian carp. Compared with the non-immunized group, non-specific immune indicators (ACP, AKP, SOD, and LZM), agglutination antibody titres of the serum, and the expression of immune-related genes (TNF-α and IL-6) of the head kidney and spleen were significantly increased in the immunized group (P < 0.01), indicating that innate and specific immune responses were induced by the CFG. In addition, the immunized fish showed higher protection than the non-immunized fish after challenge: oral control (20.00% survival); oral test (80.21% survival); injected control (6.67% survival); injected test (87.50% survival). Taken together, our research was the first to demonstrate that the constructed CFG might be developed as either oral or injected vaccines against C. freundii in aquaculture. • Citrobacter freundii CFC202 was firstly isolated from the diseased crucian carp in the Dongting Lake area of China. • Genome analysis of CFC202 showed it could mediate adhesion to cell surface through virulence factors such as hop AJ2 and fep E. • Strain CFC202 could cause attaching and effacing lesions to fish cells in vivo and in vitro. • This study was the first to construct Citrobacter freundii ghost and evaluate their immune effects in crucian carp. • Immunization with CFG vaccine in advance in crucian carp could improve disease resistance against Citrobacter freundii. [ABSTRACT FROM AUTHOR]

In this study, a Streptomyces strain was isolated from the soil samples of Yanghu Wetland Park in Changsha, Hunan Province. This strain showed excellent antimicrobial activity against 10 fish pathogens, as indicated by the results of the agar-diffusion and oxford cup assays. After 16s rDNA sequencing and physiological & biochemical analyses, it was identified as Streptomyces amritsarensis , namely for S. amritsarensis N1-32. Cytotoxicity test was performed, and the results exhibited that this strain had no toxicity to hepatic L8824 cell line from grass carp liver. The diets supplemented strain N1-32 at concentrations of 1 × 107 cfu/g and 1 × 109 cfu/g was used to feed fish. After 28 days, the expression levels of antioxidant-related genes Nrf2 and Keap1 in the liver and spleen were significantly up-regulated, and the expression of immune-related gene IgM was notably increased in the liver, kidney, head-kidney, and spleen. Toll-like receptor 4 (TLR4) gene expression was up-regulated in the spleen, and TLR4, myeloid differentiation factor 88 (MyD88) gene were up-regulated in the kidney. The survival rate of grass carp was significantly improved after pathogen infection. Whole-genome analysis of N1-32 showed that the strain harbored related genes, capability for producing substances that enhance the immunity of grass carp and inhibit pathogens. A total of 22 gene clusters were identified in the genome, including 5 terpene gene clusters, 4 nonribosomal peptide-synthetase (NRPS) gene clusters and 2 lantipeptide gene clusters. In summary, these results showed that strain N1-32 as a feed additive could regulate grass carp immunity and enhance the resistance of grass carp against fish pathogens. • A new strain, Streptomyces amritsarensis N1-32, was isolated and prospective to be applied to freshwater fish aquaculture. • Streptomyces amritsarensis N1-32 has broad-spectrum antibacterial activity against freshwater fish pathogens. • Streptomyces amritsarensis as probiotics was firstly applicated in aquaculture. • Streptomyces amritsarensis N1-32 could significantly promote the immunity and growth of grass carps. • Genome analysis of S. amritsarensis N1-32 revealed its potential for antimicrobial synthesis. [ABSTRACT FROM AUTHOR]

This study evaluated the inhibition and interaction of Bacillus velezensis BvL03 as a probiotic agent against Aeromonas hydrophila. Strain BvL03 isolated from sediment samples of fish ponds had excellent antimicrobial activity against several fish pathogenic bacteria, especially Aeromonas, including A. hydrophila, A. veronii, A. caviae, and A. sobria. The successful amplification of lipopeptide antimicrobial chemical biosynthetic genes, including iturin family (ituA, ituB, and ituD), bacillomycin family (bacA, bacD, and bacAB), surfactin family (srfAB, srfC, and srfAA), and subtilosin family (albF and sunT) from the genome of BvL03 strain, confirmed its predominant antimicrobial activity. The challenge test suggested that BvL03 significantly decreased fish mortality when challenged with A. hydrophila, which had a cumulative mortality of 12.5% in the treatment group. Toxicity and hemolytic activity of A. hydrophila after co-cultured with BvL03 were relieved as confirmed by the cell experiments, when the initial inoculated concentration of BvL03 was 109 cfu/mL or higher. Moreover, the BvL03 strain labeled with GFP protein (BvL03-GFP) and AhX040 strain labeled with mCherry protein (AhX040-mCherry) were injected into grass carps. The fluorescence levels were monitored by using In Vivo Imaging System (IVIS), in which the green color was steadily increasing, whereas the red color was gradually weakening. Whole genome sequencing revealed that strain BvL03 possesses 15 gene clusters related to antibacterial compounds, including 5 NRPS gene clusters and 3 PKS gene clusters. These results suggested that B. velezensis BvL03 has the potential to be developed as a probiotic candidate against A. hydrophila infection in aquaculture. [ABSTRACT FROM AUTHOR]

Aim: Myeloid differentiation factor 88 (MyD88) plays a key role in tumor proliferation and metastasis. Targeting MyD88 is a potent strategy in tumor therapy. TJ‐M2010‐5 is a small molecule derivative of aminothiazole and could inhibit dimer formation of MyD88. To explore the potential of TJ‐M2010‐5 in tumor therapy, we determined its antitumor effect and correlate mechanisms of TJ‐M2010‐5 in hepatocellular carcinoma (HCC). Methods: The antitumor effect of intratumoral injection of TJ‐M2010‐5 to H22 tumor‐bearing BALB/c mice was observed. Tumor growth was monitored. The expression of MyD88 and Ki‐67 were detected by immunofluorescence. In vitro, the impacts of TJ‐M2010‐5 on proliferation, cell cycle, necrosis, and apoptosis of H22 cells were evaluated. The direct and indirect effects of TJ‐M2010‐5 on macrophages were evaluated using flow cytometry. Results: TJ‐M2010‐5 induced both G0/G1 and G1/S phase arrests in HCC cells. Mechanically, downstream activation of MyD88 was suppressed by TJ‐M2010‐5 through the extracellular regulated protein kinase‐1/2/p90 ribosomal S6 kinase/glycogen synthase kinase‐3β signaling pathway. In turn, cyclin‐dependent kinase (CDK)6/cyclin D1 and CDK2/cyclin E complexes were downregulated. More importantly, TJ‐M2010‐5 significantly inhibited tumor growth in mice. Additionally, the portion of antitumor M1 macrophages (F4/80+CD11c+) in the tumor microenvironment were increased after TJ‐M2010‐5 treatment. Together, these data indicate that TJ‐M2010‐5 is a promising therapeutic drug for HCC. Conclusions: These results indicate that MyD88 is a feasible target for antitumor treatment and TJ‐M2010‐5 is a qualified candidate for HCC therapy. [ABSTRACT FROM AUTHOR]

Colorimetric biosensors are simple but effective tools that are gaining popularity due to their ability to provide low-cost, rapid, and accurate detection for viruses like the Novel coronavirus, Influenza A, and Dengue virus, especially in point-of-care testing (POCT) and visual detection. In this study, a smartphone-assisted nucleic acid POCT was built using hybridization chain reaction (HCR), magnetic beads (MBs), and oxidized 3,3′,5,5′-tetramethylbenzidine (TMB2+)-mediated etching of gold nanorods (GNRs). The application of HCR without enzyme isothermal characteristics and MBs with easy separation, can quickly amplify nucleic acid signal and remove other reaction components. The blue shift of longitudinal localized surface plasmon resonance (LSPR) based on GNRs showed significant differences in etching color for different concentrations of target nucleic acid, which convert the signal into a visually semi-quantitative colorimetric result, achieving quantitative analysis with the color recognition software built into smartphones. This strategy, which only takes 40 min to detect and is two-thirds less time than the PCR, was successfully applied for the detection of the Dengue target sequence with a detection limit of 1.25 nM and exhibited excellent specificity for distinguishing single-base mutations, indicating broad application prospects in clinical laboratory diagnosis and enriching the research of nucleic acid POCT. [Display omitted] • Smartphone-assisted POCT of nucleic acids based on HCR, MBs, and GNRs etching. • GNRs' polychromatic etching enables naked eyes visualization of nucleic acids concentration. • Semi-quantitatively with the naked eyes or quantitatively with the smartphone and took only 40 min. • This method has broad clinical and diagnostic application prospects, and enriches nucleic acids POCT research. [ABSTRACT FROM AUTHOR]

The processing efficiency and stability of ultra-hard and brittle materials plannarized by fixed abrasive pads (FAPs) are largely determined by the cutting depth and the available number of active cutting abrasives and the abrasive wear behaviors. A newly prepared agglomerated diamond (AD) abrasive embedded in FAPs has demonstrated a significant improvement on processing efficiency and stability while being used to lap hard-to-processed ceramic materials. A mathematical model was built to explain the high removal efficiency of the AD abrasives, which followed a similar trend with experimental testing results. The micro-cutting and self-sharpening capabilities of the AD abrasive, which afforded FAPs with AD abrasives to improve efficiency and stability, were manifested by our experimental examinations on the worn abrasive morphologies, the fall-out diamond chips and scratch marks left on sapphire substrates by AD abrasives. Image 1 • A novel agglomerated diamond (AD) abrasive is prepared for improving the removal efficiency and stability of sapphire. • A mathematical model on improved removal rate of AD Abrasives follows a similar trend with experimental results. • Self-sharpening mechanism of the AD abrasives in fixed abrasive lapping processes is discussed via pin-on-disk tests. • The micro-fracture feature allows the AD abrasives to self-sharpen during lapping processes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers with poor prognosis worldwide. The advent of immunotherapy has greatly improved survival in refractory patients of CRC. In this study, we aimed to identify reliable immune classification and biomarkers that predict immunotherapeutic responses in CRC patients. Based on transcriptome profiles of two publicly available CRC datasets, we performed single-sample gene set enrichment analysis (ssGSEA) to calculate the relative abundance of 29 immune-related items of each sample. Unsupervised clustering was used to classify CRC patients. Furthermore, an immune prognostic signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The CRC patients were clustered into high, medium, low immune infiltration subtypes based on the immune landscape. There was significant heterogeneity among the three subtypes. The high immune infiltration group showed higher expression of programmed cell death-ligand 1 and better prognosis than the median and low immune infiltration groups. Furthermore, we constructed a 7-immune-related prognostic gene signature and found that the signature had high predictive value and was superior to other clinicopathological parameters. Finally, the correlation analysis of the signature with immune cell infiltration and immune checkpoint molecules suggested that the signature had the potential to assess the immunotherapeutic responses of CRC patients. The immune landscape and prognostic signature of CRC contribute to a deeper understanding of the tumor microenvironment and guide accurate immunotherapy. • Immune landscape of the tumor microenvironment in colorectal cancer was fully depicted. • An immune-related prognostic signature was constructed based on the immune landscape. • The signature can effectively predict the prognosis and immunotherapeutic responses of colorectal cancer [ABSTRACT FROM AUTHOR]

• An immune prognostic signature based on 16 IRGs in colorectal cancer was established. • The signature showed considerable value in predicting the prognosis of colorectal cancer. • Significant effectiveness of the predictive performance was shown in clinical subgroups. • The signature could reflect the patient's immune status and immunotherapy response. Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although the significant efficacy of immunotherapy has been shown, only limited CRC patients benefit from it. Therefore, we aimed to establish a prognostic signature based on immune-related genes (IRGs) to predict overall survival (OS) and the potential response to immunotherapy in CRC patients. Gene expression profiles and clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic signature composed of IRGs was established using univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis. CIBERSORT was used to estimate the immune cell infiltration. A total of 24 survival-related IRGs were identified from 247 differentially expressed IRGs. Then, 16 IRGs were selected to establish the prognostic signature that stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The AUCs of the time-dependent ROC curves indicated that the signature had a strong predictive accuracy in internal and external validation sets. Multivariate cox regression analysis suggested that the signature could also act as an independent prognostic factor for OS. The low-risk group had a higher proportion of immune cell infiltration than the high-risk group, such as CD4 memory resting T cells, activated dendritic cells, and resting dendritic cells. In addition, patients in the high-risk group exhibited higher tumor mutation burden and BRAF mutation. We developed an immune-related prognostic signature to predict the OS and immune status in CRC patients. We believed that our signature is conducive to better stratification and more precise immunotherapy for CRC patients. [ABSTRACT FROM AUTHOR]

Further to explore the effect of the agglomerated diamond (AD) abrasive wear on material removal behavior of sapphire in lapping, the pin-on-disk test with an AD abrasive was carried out. The classifications of AD abrasive wear, material removal behavior of sapphire, friction coefficient of sliding contact and removal ratio of sapphire material were thoroughly investigated. The wear behavior of the AD abrasive shows two types: attrition wear and micro-fracture. Three wear statuses of the active cutting diamond grains fixed on the AD abrasive surface, including attrition wear, worn-flat and pull-out, occur in the tests. The sapphire material is mainly removed by the AD abrasive via plastic deformation. The micro-fracture feature of the AD abrasive improves its self-sharpening ability. Therefore, the micro-cutting action of the AD abrasive on the sapphire wafer has behaved well. Unlabelled Image • Three wear statuses of the active cutting diamond grains fixed on the agglomerated diamond (AD) abrasive surface include attrition wear, worn-flat and pull-out. • Material is mainly removed via plastic deformation in the case of AD abrasive wear from the viewpoints of scratches and sapphire chips. • Cutting force ratio and friction coefficient in AD abrasive wear process are more stable than those in single crystalline diamond abrasive wear process. • AD abrasive wear behavior is propitious to sapphire material removal process. [ABSTRACT FROM AUTHOR]

Background: The development of new treatment strategies to improve peripheral nerve repair after injury, especially those that accelerate axonal nerve regeneration, is very important. The aim of this study is to elucidate the molecular mechanisms of how bone marrow stromal cell (BMSC)-derived exosomes (EXOs) participate in peripheral nerve regeneration and whether the regenerative effect of EXOs is correlated with dose. Method: BMSCs were transfected with or without an siRNA targeting Ago2 (SiAgo2). EXOs extracted from the BMSCs were administered to dorsal root ganglion (DRG) neurons in vitro. After 48 h of culture, the neurite length was measured. Moreover, EXOs at four different doses were injected into the gastrocnemius muscles of rats with sciatic nerve crush injury. The sciatic nerve functional index (SFI) and latency of thermal pain (LTP) of the hind leg sciatic nerve were measured before the operation and at 7, 14, 21, and 28 days after the operation. Then, the number and diameter of the regenerated fibers in the injured distal sciatic nerve were quantified. Seven genes associated with nerve regeneration were investigated by qRT-PCR in DRG neurons extracted from rats 7 days after the sciatic nerve crush. Results: We showed that after 48 h of culture, the mean number of neurites and the length of cultured DRG neurons in the SiAgo2-BMSC-EXO and SiAgo2-BMSC groups were smaller than that in the untreated and siRNA control groups. The average number and diameter of regenerated axons, LTP, and SFI in the group with 0.9 × 1010 particles/ml EXOs were better than those in other groups, while the group that received a minimum EXO dose (0.4 × 1010 particles/ml) was not significantly different from the PBS group. The expression of PMP22, VEGFA, NGFr, and S100b in DRGs from the EXO-treated group was significantly higher than that in the PBS control group. No significant difference was observed in the expression of HGF and Akt1 among the groups. Conclusions: These results showed that BMSC-derived EXOs can promote the regeneration of peripheral nerves and that the mechanism may involve miRNA-mediated regulation of regeneration-related genes, such as VEGFA. Finally, a dose-effect relationship between EXO treatment and nerve regeneration was shown. [ABSTRACT FROM AUTHOR]

Auristatin PE (PE) as an anti-microtubule agent possesses good anticancer activity. However, the poor target effect and strong side effect limit its clinical applications. Targeted delivery of PE may overcome the disadvantages associated with PE, being very conducive to continuing clinical trials of PE. Boron nitride nanotubes (BNNTs) with unique physical and chemical properties have attracted considerable attention in drug delivery. Herein, a targeted drug delivery strategy based on folate-conjugated boron nitride nanotubes (BNNTs-FA) was used to improve the efficacy of PE. It was found that PE was successfully loaded onto BNNTs-FA via π-π stacking and hydrogen bonding interactions. BNNTs-FA@PE exhibited stronger cytotoxicity to Hep G2 cells than free PE and BNNTs@PE complexes due to the increased cellular uptake of PE mediated by the FA receptor. BNNTs-FA@PE showed excellent antiproliferative activities in a dose- and time-dependent manner. Furthermore, BNNTs-FA@PE induced apoptosis of Hep G2 cells via an intrinsic mitochondria–mediated pathway by reducing the mitochondrial membrane potential, activating Caspase-9 and Caspase-3. The construction of BNNTs-FA@PE system successfully improves the target effect of PE and may be very promising for the treatment of liver cancer in the future. • The targeted Auristatin PE-delivery system is designed and fabricated based on folate-conjugated boron nitride nanotubes. • Auristatin PE is successfully loaded onto BNNTs-FA via π-π stacking and hydrogen bonding interactions. • Auristatin PE can be transported into the cells via folate receptor-mediated endocytosis pathway. • This complex possesses preferable anticancer activity and can induce cells apoptosis via a mitochondria–mediated pathway. [ABSTRACT FROM AUTHOR]

Fixed abrasive is taking the place of loose abrasive owing to its high efficiency and little pollution. The self-conditioning ability of fixed abrasive pads (FAPs) plays a favorable role in the lapping process. In this paper, agglomerated diamond (AD) abrasives were prepared for the sapphire lapping process. Material removal rate (MRR), material removal rate variation (MRRV) and surface topography of sapphire wafers lapped by fixed AD abrasive pad were investigated. Abrasive wear and wear debris were characterized. The material removal mechanisms of AD abrasives were discussed. Comparison of mechanical properties between AD and SD in abrasive wear process was analyzed. Influence of mechanical properties of AD abrasives on processing performance was explained. Comparing with fixed single diamond (SD) abrasive pads, the higher MRR, the lower MRRV and surface roughness of sapphire wafer were obtained in the fixed AD abrasive lapping process. Stable large protrusion height and consecutive sharp edges of AD abrasives ensure the excellent lapping performance. The protrusion height of abrasives is positive correlated with the self-conditioning ability of FAPs. The stable protrusion height of AD abrasives is attribute to two points: one is the rough surface of an AD abrasive with multiple sharp cutting edges improves the bonding strength between the abrasives and the pad matrix; the other is the detached diamond particles due to the micro-fracture phenomenon of AD abrasives accelerates the abrasion of matrix. Unlabelled Image • Agglomerated diamond (AD) abrasives with multiple cutting edges are prepared of diamond and ceramics. • Mechanical properties of AD abrasives, including micro-fracture property, are evaluated. • Material removal characteristics of AD abrasives in the case of abrasive wear are analyzed. • Relationship between mechanical properties and processing performance of AD abrasives is confirmed. [ABSTRACT FROM AUTHOR]