Improved Bending Strength and Thermal Conductivity of Diamond/Al Composites with Ti Coating Fabricated by Liquid-Solid Separation Method.

In response to the rapid development of high-performance electronic devices, diamond/Al composites with high thermal conductivity (TC) have been considered as the latest generation of thermal management materials. This study involved the fabrication of diamond/Al composites reinforced with Ti-coated diamond particles using a liquid-solid separation (LSS) method. The interfacial characteristics of composites both without and with Ti coatings were evaluated using SEM, XRD, and EMPA. The results show that the LSS technology can fabricate diamond/Al composites without Al4C3, hence guaranteeing excellent mechanical and thermophysical properties. The higher TC of the diamond/Al composite with a Ti coating was attributed to the favorable metallurgical bonding interface compounds. Due to the non-wettability between diamond and Al, the TC of uncoated diamond particle-reinforced composites was only 149 W/m·K. The TC of Ti-coated composites increased by 85.9% to 277 W/m·K. A simultaneous comparison and analysis were performed on the features of composites reinforced by Ti and Cr coatings. The results suggest that the application of the Ti coating increases the bending strength of the composite, while the Cr coating enhances the TC of the composite. We calculate the theoretical TC of the diamond/Al composite by using the differential effective medium (DEM) and Maxwell prediction model and analyze the effect of Ti coating on the TC of the composite.

Change in Hydrogen Trapping Characteristics and Influence on Hydrogen Embrittlement Sensitivity in a Medium-Carbon, High-Strength Steel: The Effects of Heat Treatments.

Medium-carbon, high-strength steels are widely used in the field of hydrogen energy because of their good mechanical properties, and they can be readily tailored by heat treatment processes such as the normalizing-tempering (N&T) and quenching-tempering (Q&T) methods. The hydrogen embrittlement (HE) susceptibility of a medium-carbon, high-strength steel was investigated utilizing microstructural characterization with scanning electron microscopy (SEM), the electron backscatter diffraction (EBSD) technique, and transmission electron microscopy (TEM). A study was also conducted on the steel's hydrogen transport behavior as affected by the N&T and Q&T treatments. The steel contained more hydrogen traps, such as dislocations, grain boundaries, lath boundaries, and carbide interfaces, after the Q&T process, which was associated with a lower HE sensitivity when comparing the two treatments. In comparison, the N&T process produced larger-size and lesser-density carbides distributed along the grain boundaries, and this resulted in a relatively higher HE susceptibility, as revealed by the slow-strain-rate tensile (SSRT) tests of the hydrogen-charged steels and by the fractographic study of the fracture surface.

Data Augmentation of a Corrosion Dataset for Defect Growth Prediction of Pipelines Using Conditional Tabular Generative Adversarial Networks.

Due to corrosion characteristics, there are data scarcity and uneven distribution in corrosion datasets, and collecting high-quality data is time-consuming and sometimes difficult. Therefore, this work introduces a novel data augmentation strategy using a conditional tabular generative adversarial network (CTGAN) for enhancing corrosion datasets of pipelines. Firstly, the corrosion dataset is subjected to data cleaning and variable correlation analysis. The CTGAN is then used to generate external environmental factors as input variables for corrosion growth prediction, and a hybrid model based on machine learning is employed to generate corrosion depth as an output variable. The fake data are merged with the original data to form the synthetic dataset. Finally, the proposed data augmentation strategy is verified by analyzing the synthetic dataset using different visualization methods and evaluation indicators. The results show that the synthetic and original datasets have similar distributions, and the data augmentation strategy can learn the distribution of real corrosion data and sample fake data that are highly similar to the real data. Predictive models trained on the synthetic dataset perform better than predictive models trained using only the original dataset. In comparative tests, the proposed strategy outperformed other data generation methods.

Recognition of glycoside hydrolase 12 proteins by the immune receptor RXEG1 confers Fusarium head blight resistance in wheat.

Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease in wheat (Triticum aestivum) that results in substantial yield losses and mycotoxin contamination. Reliable genetic resources for FHB resistance in wheat are lacking. In this study, we characterized glycoside hydrolase 12 (GH12) family proteins secreted by F. graminearum. We established that two GH12 proteins, Fg05851 and Fg11037, have functionally redundant roles in F. graminearum colonization of wheat. Furthermore, we determined that the GH12 proteins Fg05851 and Fg11037 are recognized by the leucine-rich-repeat receptor-like protein RXEG1 in the dicot Nicotiana benthamiana. Heterologous expression of RXEG1 conferred wheat responsiveness to Fg05851 and Fg11037, enhanced wheat resistance to F. graminearum and reduced levels of the mycotoxin deoxynivalenol in wheat grains in an Fg05851/Fg11037-dependent manner. In the RXEG1 transgenic lines, genes related to pattern-triggered plant immunity, salicylic acid, jasmonic acid, and anti-oxidative homeostasis signalling pathways were upregulated during F. graminearum infection. However, the expression of these genes was not significantly changed during infection by the deletion mutant ΔFg05851/Fg11037, suggesting that the recognition of Fg05851/Fg11037 by RXEG1 triggered plant resistance against FHB. Moreover, introducing RXEG1 into three other different wheat cultivars via crossing also conferred resistance to F. graminearum. Expression of RXEG1 did not have obvious deleterious effects on plant growth and development in wheat. Our study reveals that N. benthamiana RXEG1 remains effective when transferred into wheat, a monocot, which in turn suggests that engineering wheat with interfamily plant immune receptor transgenes is a viable strategy for increasing resistance to FHB.

Small molecule angiotensin converting enzyme inhibitors: A medicinal chemistry perspective.

Angiotensin-converting enzyme (ACE), a zinc metalloprotein, is a central component of the renin-angiotensin system (RAS). It degrades bradykinin and other vasoactive peptides. Angiotensin-converting-enzyme inhibitors (ACE inhibitors, ACEIs) decrease the formation of angiotensin II and increase the level of bradykinin, thus relaxing blood vessels as well as reducing blood volume, lowering blood pressure and reducing oxygen consumption by the heart, which can be used to prevent and treat cardiovascular diseases and kidney diseases. Nevertheless, ACEIs are associated with a range of adverse effects such as renal insufficiency, which limits their use. In recent years, researchers have attempted to reduce the adverse effects of ACEIs by improving the selectivity of ACEIs for structural domains based on conformational relationships, and have developed a series of novel ACEIs. In this review, we have summarized the research advances of ACE inhibitors, focusing on the development sources, design strategies and analysis of structure-activity relationships and the biological activities of ACE inhibitors.

Roles of Al2O3@ZrO2 Particles in Modulating Crystalline Morphology and Electrical Properties of P(VDF-HFP) Nanocomposites.

Polymer materials with excellent physicochemical and electrical properties are desirable for energy storage applications in advanced electronics and power systems. Here, Al2O3@ZrO2 nanoparticles (A@Z) with a core-shell structure are synthesized and introduced to a P(VDF-HFP) matrix to fabricate P(VDF-HFP)/A@Z nanocomposite films. Experimental and simulation results confirm that A@Z nanoparticles increase the crystallinity and crystallization temperature owing to the effect of the refined crystal size. The incorporation of A@Z nanoparticles leads to conformational changes of molecular chains of P(VDF-HFP), which influences the dielectric relaxation and trap parameters of the nanocomposites. The calculated total trapped charges increase from 13.63 µC of the neat P(VDF-HFP) to 47.55 µC of P(VDF-HFP)/5 vol%-A@Z nanocomposite, indicating a substantial improvement in trap density. The modulated crystalline characteristic and interfaces between nanoparticles and polymer matrix are effective in inhibiting charge motion and impeding the electric conduction channels, which contributes to an improved electrical property and energy density of the nanocomposites. Specifically, a ~200% and ~31% enhancement in discharged energy density and breakdown strength are achieved in the P(VDF-HFP)/5 vol%-A@Z nanocomposite.

Microstructural Effects in the Development of Near-Neutral pH Stress Corrosion Cracks in Pipelines.

The corrosion and stress corrosion cracking (SCC) behaviors of 20#, X60, and X80 pipeline steels in a near-neutral pH environment were investigated by means of electrochemical measurement, immersion test, and interrupted slow strain rate tensile (SSRT) test. The propensity for SCC, as indicated by the stress threshold value for crack initiation, was found to be dependent on the type of steel microstructure. Cracks were initiated in the high-strength steel X80 at a stress less than its yield strength, whereas in the other lower-grade steels, the initiation of cracks occurred after the yielding point. The threshold stress of SCC initiation in the near-neutral pH environment for 20#, X60, and X80 steels were 130.64% σys, 106.79% σys, and 86.92% σys, respectively. The SCC of 20# and X60 were characterized by the formation of transgranular and intergranular cracks, while X80 steel was only by transgranular cracking. The occurrence of corrosion had a great effect on crack initiation and the growth at the later stage. The latter involved hydrogen effects. A correlation between SCC sensitivity and the yield strength of the steel has been identified.

Research trends and hotspot analysis of fractional carbon dioxide laser: A bibliometric and visualized analysis via Citespace.

INTRODUCTION: There is limited basic research on carbon dioxide (CO2 ) fractional laser, indicating blind spots in CO2 fractional laser treatment of certain diseases. This study aimed to organize previous literature, summarize the current research, and speculate on possible future development. METHODS: We searched document data on fractional CO2 lasers from the Web of Science core collection database and retrieved 928 articles from 2004 to 2021. CiteSpace software was used to analyze the main institutions, authors, subject hotspots, and research frontiers in global CO2 fractional laser research. RESULTS: The results revealed that 928 related papers were published in the past 18 years (2004-2021), and the number has increased annually. The publications were written by 3239 authors from 626 institutions in 60 countries/regions. The United States (US) dominates this field (312 documents), followed by Italy (289), and South Korea (88). Lasers in Surgery and Medicine is the journal with the most publications and citations, and Uebelhoer is the central author. The main research hotspots include vulvovaginal atrophy, fractional photothermolysis, keloids, drug delivery, gene expressions, facial acne scarring, resurfacing, vitiligo, and photo damage. CONCLUSION: Using CiteSpace, this paper draws a map of authors, institutions, and keywords in fractional CO2 laser from 2004 to 2021; summarizes the main authors, institutions, research hotspots, and cutting-edge topics of global fractional CO2 laser technology in recent years; and summarizes the current application status of global fractional CO2 laser in disease treatment. It also provides new ideas for the future application and research of fractional CO2 lasers.

TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids.

Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.

Neutrophils and their extracellular traps impair ablative fractional carbon dioxide laser-induced dermal remolding in mice.

OBJECTIVES: Ablative fractional CO2 laser (AFL) therapy is an effective intervention to induce dermal remodeling. AFL treatment of the skin triggers the recruitment of immune cells, with neutrophils dominating the early phase. However, the role of recruited neutrophils in AFL-induced microinjuries and their subsequent dermal remodeling capacity remains elusive. MATERIALS AND METHODS: A mouse model of AFL-induced dermal remodeling was established. RNA sequencing was used to identify the prominent features of AFL-treated tissues. Histological analysis, including H&E and Masson staining, ultrastructure observation by transmission microscopy, immunofluorescence, and quantitative real-time polymerase chain reaction were used for dermal remodeling analysis. Moreover, AFL-treated mice were intraperitoneally injected with anti-mouse Ly6G antibodies to deplete neutrophils. Neutrophil extracellular traps (NETs) were explored using immunofluorescence, transmission microscopy, and in vitro coculture experiments. RESULTS: Dermal remodeling, characterized by an increased number of CD31-positve vessels and elevated messenger RNA (mRNA) expression of genes encoding transforming growth factor-ß (TGF-ß), collagen I, and collagen III, was observed at 15 days after AFL treatment. In the AFL-induced inflammation phase, RNA sequencing identified neutrophil chemotaxis, and degranulation genes were significantly enriched. Histology and immunofluorescence staining of human and mouse tissues harvested at Day 1 after AFL treatment revealed significant neutrophil infiltration surrounding thermal-induced microinjuries. Neutrophil depletion decreased the expression of stress-related genes such as S100A8 and S100A9 in the early phase following AFL treatment. Importantly, neutrophil depletion enhanced dermal remodeling at Day 15, as reflected by enrichment of the extracellular matrix and collagen biosynthesis genes based on RNA sequencing. Moreover, increased collagen I, collagen III, and TGF-ß mRNA expression, increased cell proliferation, and vascularity were observed. Interestingly, NETs, which could be induced by AFL-treated fibroblasts in vitro, were identified in both human and mouse tissues on Day 1 after AFL treatment. CONCLUSIONS: AFL-treated human and mouse skin recruited a large number of neutrophils. The neutrophil surge impaired dermal remodeling in mice. The microenvironment and fibroblast functional modulation mediated by neutrophil degranulation and NET formation were determined to be the underlying mechanisms. Our results indicate that modification of infiltrated neutrophil activity might be a potential therapeutic target for AFL-induced dermal remodeling.

Plant immunity inducers: from discovery to agricultural application.

While conventional chemical fungicides directly eliminate pathogens, plant immunity inducers activate or prime plant immunity. In recent years, considerable progress has been made in understanding the mechanisms of immune regulation in plants. The development and application of plant immunity inducers based on the principles of plant immunity represent a new field in plant protection research. In this review, we describe the mechanisms of plant immunity inducers in terms of plant immune system activation, summarize the various classes of reported plant immunity inducers (proteins, oligosaccharides, chemicals, and lipids), and review methods for the identification or synthesis of plant immunity inducers. The current situation, new strategies, and future prospects in the development and application of plant immunity inducers are also discussed.

Fabrication of Functionally Graded Diamond/Al Composites by Liquid-Solid Separation Technology.

The electronic packaging shell, the necessary material for hermetic packaging of large microelectronic device chips, is made by mechanical processing of a uniform block. However, the property variety requirements at different positions of the shell due to the performance have not been solved. An independently developed liquid-solid separation technology is applied to fabricate the diamond/Al composites with a graded distribution of diamond particles. The diamond content decreases along a gradient from the bottom of the shell, which houses the chips, to the top of the shell wall, which is welded with the cover plate. The bottom of the shell has a thermal conductivity (TC) of 169 W/mK, coefficient of thermal expansion (CTE) of 11.0 × 10-6/K, bending strength of 88 MPa, and diamond content of 48 vol.%. The top of the shell has a TC of 108 W/mK, CTE of 19.3 × 10-6/K, bending strength of 175 MPa, and diamond content of 15 vol.%, which solves the special requirements of different parts of the shell and helps to improve the thermal stability of packaging components. Moreover, the interfacial characteristics are also investigated. This work provides a promising approach for the preparation of packaging shells by near-net shape forming.

The Phytophthora effector Avh241 interacts with host NDR1-like proteins to manipulate plant immunity.

Plant pathogens rely on effector proteins to suppress host innate immune responses and facilitate colonization. Although the Phytophthora sojae RxLR effector Avh241 promotes Phytophthora infection, the molecular basis of Avh241 virulence remains poorly understood. Here we identified non-race specific disease resistance 1 (NDR1)-like proteins, the critical components in plant effector-triggered immunity (ETI) responses, as host targets of Avh241. Avh241 interacts with NDR1 in the plasma membrane and suppresses NDR1-participated ETI responses. Silencing of GmNDR1s increases the susceptibility of soybean to P. sojae infection, and overexpression of GmNDR1s reduces infection, which supports its positive role in plant immunity against P. sojae. Furthermore, we demonstrate that GmNDR1 interacts with itself, and Avh241 probably disrupts the self-association of GmNDR1. These data highlight an effective counter-defense mechanism by which a Phytophthora effector suppresses plant immune responses, likely by disturbing the function of NDR1 during infection.

Endoplasmic reticulum-associated degradation is required for nephrin maturation and kidney glomerular filtration function.

Podocytes are key to the glomerular filtration barrier by forming a slit diaphragm between interdigitating foot processes; however, the molecular details and functional importance of protein folding and degradation in the ER remain unknown. Here, we show that the SEL1L-HRD1 protein complex of ER-associated degradation (ERAD) is required for slit diaphragm formation and glomerular filtration function. SEL1L-HRD1 ERAD is highly expressed in podocytes of both mouse and human kidneys. Mice with podocyte-specific Sel1L deficiency develop podocytopathy and severe congenital nephrotic syndrome with an impaired slit diaphragm shortly after weaning and die prematurely, with a median lifespan of approximately 3 months. We show mechanistically that nephrin, a type 1 membrane protein causally linked to congenital nephrotic syndrome, is an endogenous ERAD substrate. ERAD deficiency attenuated the maturation of nascent nephrin, leading to its retention in the ER. We also show that various autosomal-recessive nephrin disease mutants were highly unstable and broken down by SEL1L-HRD1 ERAD, which attenuated the pathogenicity of the mutants toward the WT allele. This study uncovers a critical role of SEL1L-HRD1 ERAD in glomerular filtration barrier function and provides insights into the pathogenesis associated with autosomal-recessive disease mutants.

Fg12 ribonuclease secretion contributes to Fusarium graminearum virulence and induces plant cell death.

Filamentous fungal pathogens secrete effectors that modulate host immunity and facilitate infection. Fusarium graminearum is an important plant pathogen responsible for various devastating diseases. However, little is known about the function of effector proteins secreted by F. graminearum. Herein, we identified several effector candidates in the F. graminearum secretome. Among them, the secreted ribonuclease Fg12 was highly upregulated during the early stages of F. graminearum infection in soybean; its deletion compromised the virulence of F. graminearum. Transient expression of Fg12 in Nicotiana benthamiana induced cell death in a light-dependent manner. Fg12 possessed ribonuclease (RNase) activity, degrading total RNA. The enzymatic activity of Fg12 was required for its cell death-promoting effects. Importantly, the ability of Fg12 to induce cell death was independent of BAK1/SOBIR1, and treatment of soybean with recombinant Fg12 protein induced resistance to various pathogens, including F. graminearum and Phytophthora sojae. Overall, our results provide evidence that RNase effectors not only contribute to pathogen virulence but also induce plant cell death.

Remineralization of enamel caries by an amelogenin-derived peptide and fluoride in vitro.

Dental caries is one of the most common oral diseases in the world. This study was tantamount to investigate the combinatory effects of an amelogenin-derived peptide (called QP5) and fluoride on the remineralization of artificial enamel caries. The peptide QP5 was synthesized and characterized, and the binding capability of the peptide on hydroxyapatite (HA) and demineralized tooth enamel surface was analysed. Then, the mineralization function of the peptide and fluoride was studied through the spontaneous mineralization testing and remineralization on enamel caries in vitro. First, the novel peptide QP5 could bind on the hydroxyapatite and demineralized tooth enamel surfaces. Second, QP5 can transitorily stabilize the formation of amorphous calcium phosphate and direct the transformation into hydroxyapatite crystals alone and in combination with fluoride. In addition, compared to blocks treated by peptide QP5 alone or fluoride, the sample blocks showed significantly higher surface microhardness, lower mineral loss and shallower lesion depth after treatment with a combination of QP5 and fluoride at high or low concentrations. The peptide QP5 could control the crystallization of hydroxyapatite, and combinatory application of peptide QP5 and fluoride had a potential synergistic effect on the remineralization of enamel caries.

The effects of 8DSS peptide on remineralization in a rat model of enamel caries evaluated by two nondestructive techniques.

Nowadays, dental caries is one of the most common oral health problems, affecting most individuals. It has been found that, by remineralizing enamel at an early stage in the formation of enamel caries, teeth can be effectively protected from dental caries. In this work, a peptide with eight repetitive sequences of aspartate-serine-serine (8DSS) is applied as the bio-mineralizer in an in-vivo rat enamel caries model. Nondestructive quantitative light-induced fluorescence-digital (QLF-D) imaging and micro-computed tomography (micro-CT) are used to evaluate the remineralization of enamel carious lesions by measuring the total fluorescence radiance loss of the molar area (Δ QTotal), acquired using QLF-D imaging, and the mineral density and residual molar enamel volume, acquired using micro-CT. Correlations are explored between Δ QTotal and mineral density (strong correlation, r = 0.8000, p < 0.001) and Δ QTotal and residual molar enamel volume (moderate correlation, r = 0.6375, p < 0.001). Our results demonstrate that 8DSS is a promising in-vivo remineralization agent that exhibits comparable effects to NaF ( p < 0.05), which has been verified using the classical Keyes method. Moreover, the nondestructive QLF-D and micro-CT methods can be combined to quantify the remineralization of enamel carious lesions three-dimensionally in vivo, making them broadly applicable in quantifying hard tissues.

Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.

Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5 Šcrystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs.

iTRAQ-based quantitative analysis of age-specific variations in salivary proteome of caries-susceptible individuals.

BACKGROUND: Human saliva is a protein-rich, easily accessible source of potential biomarkers for the diagnosis of oral and systemic diseases. However, little is known about the changes in salivary proteome associated with aging of patients with dental caries. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) in combination with multiple reaction monitoring mass spectrometry (MRM-MS) to characterize the salivary proteome profiles of subjects of different ages, presenting with and without caries, with the aim of identifying age-related biomarkers for dental caries. METHODS: Unstimulated whole saliva samples were collected from 40 caries-free and caries-susceptible young adults and elderly individuals. Salivary proteins were extracted, reduced, alkylated, digested with trypsin and then analyzed using iTRAQ-coupled LC-MS/MS, followed by GO annotation, biological pathway analysis, hierarchical clustering analysis, and protein-protein interaction analysis. Candidate verification was then conducted using MRM-MS. RESULTS: Among 658 salivary proteins identified using tandem mass spectrometry, 435 proteins exhibited altered expression patterns in different age groups with and without caries. Of these proteins, 96 displayed age-specific changes among caries-susceptible adults and elderly individuals, and were mainly associated with salivary secretion pathway, while 110 age-specific proteins were identified among healthy individuals. It was found that the age factor caused significant variations and played an important role in both healthy and cariogenic salivary proteomes. Subsequently, a total of 136 target proteins with complex protein-protein interactions, including 14 age-specific proteins associated with caries, were further successfully validated using MRM analysis. Moreover, non-age-specific proteins (histatin-1 and BPI fold-containing family B member 1) were verified to be important candidate biomarkers for common dental caries. CONCLUSIONS: Our proteomic analysis performed using the discovery-through-verification pipeline revealed distinct variations caused by age factor in both healthy and cariogenic salivary proteomes, highlighting the significance of age in the great potential of saliva for caries diagnosis and biomarker discovery.