RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells.

The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.

MYO1F regulates antifungal immunity by regulating acetylation of microtubules.

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9 Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow-derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

Binary Sulfiphilic Nickel Boride on Boron-Doped Graphene with Beneficial Interfacial Charge for Accelerated Li-S Dynamics.

The "shuttle effect" and slow conversion kinetics of lithium polysulfides (LiPSs) are stumbling block for high-energy-density lithium-sulfur batteries (LSBs), which can be effectively evaded by advanced catalytic materials. Transition metal borides possess binary LiPSs interactions sites, aggrandizing the density of chemical anchoring sites. Herein, a novel core-shelled heterostructure consisting of nickel boride nanoparticles on boron-doped graphene (Ni3 B/BG), is synthesized through a graphene spontaneously couple derived spatially confined strategy. The integration of Li2 S precipitation/dissociation experiments and density functional theory computations demonstrate that the favorable interfacial charge state between Ni3 B and BG provides smooth electron/charge transport channel, which promotes the charge transfer between Li2 S4 -Ni3 B/BG and Li2 S-Ni3 B/BG systems. Benefitting from these, the facilitated solid-liquid conversion kinetics of LiPSs and reduced energy barrier of Li2 S decomposition are achieved. Consequently, the LSBs employed the Ni3 B/BG modified PP separator deliver conspicuously improved electrochemical performances with excellent cycling stability (decay of 0.07% per cycle for 600 cycles at 2 C) and remarkable rate capability of 650 mAh g-1 at 10 C. This study provides a facile strategy for transition metal borides and reveals the effect of heterostructure on catalytic and adsorption activity for LiPSs, offering a new viewpoint to apply boride in LSBs.

Cutting Edge: EPHB2 Is a Coreceptor for Fungal Recognition and Phosphorylation of Syk in the Dectin-1 Signaling Pathway.

Invasive fungal infections have become a leading cause of death among immunocompromised patients, leading to around 1.5 million deaths per year globally. The molecular mechanisms by which hosts defend themselves against fungal infection remain largely unclear, which impedes the development of antifungal drugs and other treatment options. In this article, we show that the tyrosine kinase receptor EPH receptor B2 (EPHB2), together with dectin-1, recognizes ß-glucan and activates downstream signaling pathways. Mechanistically, we found that EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation after dectin-1 ligand stimulation, whereas dectin-1 is critical for the recruitment of Syk. Ephb2-deficient mice are susceptible to Candida albicans-induced fungemia model, which also supports the role of EPHB2 in antifungal immunity. Overall, we provide evidence that EPHB2 is a coreceptor for the recognition of dectin-1 ligands and plays an essential role in antifungal immunity by phosphorylating Syk.

Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases.

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.

[Research and Design of Automatic Test System for Ventilator Performance].

Ventilator is an important medical instrument which can replace the function of autonomous ventilation artificially. Its safety and reliability are related to the health and even life safety of patients. With the publishing of the new national standard and international standard for ventilators, higher requirements are put forward for the detection and evaluation. This study mainly introduces an automatic test system for ventilator performance. The test system is based on PF-300 air-flow analyzer of Imtmedical and standard simulation lung. The automatic switch module of simulation lung is developed, and the automatic test system of ventilator is designed using the software development platform based on Python. It can not only automatically test all ventilation control parameters and monitoring parameters of the ventilator, but also realize automatic data recording, form reports and data analysis, and improve the efficiency and quality of inspection, detection and quality control.

Classification of multi-differentiated liver cancer pathological images based on deep learning attention mechanism.

PURPOSE: Liver cancer is one of the most common malignant tumors in the world, ranking fifth in malignant tumors. The degree of differentiation can reflect the degree of malignancy. The degree of malignancy of liver cancer can be divided into three types: poorly differentiated, moderately differentiated, and well differentiated. Diagnosis and treatment of different levels of differentiation are crucial to the survival rate and survival time of patients. As the gold standard for liver cancer diagnosis, histopathological images can accurately distinguish liver cancers of different levels of differentiation. Therefore, the study of intelligent classification of histopathological images is of great significance to patients with liver cancer. At present, the classification of histopathological images of liver cancer with different degrees of differentiation has disadvantages such as time-consuming, labor-intensive, and large manual investment. In this context, the importance of intelligent classification of histopathological images is obvious. METHODS: Based on the development of a complete data acquisition scheme, this paper applies the SENet deep learning model to the intelligent classification of all types of differentiated liver cancer histopathological images for the first time, and compares it with the four deep learning models of VGG16, ResNet50, ResNet_CBAM, and SKNet. The evaluation indexes adopted in this paper include confusion matrix, Precision, recall, F1 Score, etc. These evaluation indexes can be used to evaluate the model in a very comprehensive and accurate way. RESULTS: Five different deep learning classification models are applied to collect the data set and evaluate model. The experimental results show that the SENet model has achieved the best classification effect with an accuracy of 95.27%. The model also has good reliability and generalization ability. The experiment proves that the SENet deep learning model has a good application prospect in the intelligent classification of histopathological images. CONCLUSIONS: This study also proves that deep learning has great application value in solving the time-consuming and laborious problems existing in traditional manual film reading, and it has certain practical significance for the intelligent classification research of other cancer histopathological images.

The application of feature engineering in establishing a rapid and robust model for identifying patients with glioma.

The aim of the study is to evaluate the efficacy of the combination of Raman spectroscopy with feature engineering and machine learning algorithms for detecting glioma patients. In this study, we used Raman spectroscopy technology to collect serum spectra of glioma patients and healthy people and used feature engineering-based classification models for prediction. First, to reduce the dimensionality of the data, we used two feature extraction algorithms which are partial least squares (PLS) and principal component analysis (PCA). Then, the principal components were selected using the feature selection methods of four correlation indexes, namely, Relief-F (RF), the Pearson correlation coefficient (PCC), the F-score (FS) and term variance (TV). Finally, back-propagation neural network (BP), linear discriminant analysis (LDA) and support vector machine (SVM) classification models were established. To improve the reliability of the model, we used a fivefold cross validation to measure the prediction performance between different models. In this experiment, 33 classification models were established. Integrating 4 classification criteria, PLS-Relief-F-BP, PLS-F-Score-BP, PLS-LDA and PLS-Relief-F-SVM had better effects, and their accuracy rates reached 97.58%, 96.33%, 97.87% and 96.19%, respectively. The experimental results show that feature engineering can select more representative features, reduce computational time complexity and simplify the model. The classification model established in this experiment can not only increase the robustness of the model and shorten the discrimination time but also realize the rapid, stable and accurate diagnosis of glioma patients, which has high clinical application value.

Variations of stress field and stone fracture produced at different lateral locations in a shockwave lithotripter field.

During clinical procedures, the lithotripter shock wave (LSW) that is incident on the stone and resultant stress field is often asymmetric due to the respiratory motion of the patient. The variations of the LSW-stone interaction and associated fracture pattern were investigated by photoelastic imaging, phantom experiments, and three-dimensional fluid-solid interaction modeling at different lateral locations in a lithotripter field. In contrast to a T-shaped fracture pattern often observed in the posterior region of the disk-shaped stone under symmetric loading, the fracture pattern gradually transitioned to a tilted L-shape under asymmetric loading conditions. Moreover, the model simulations revealed the generation of surface acoustic waves (SAWs), i.e., a leaky Rayleigh wave on the anterior boundary and Scholte wave on the posterior boundary of the stone. The propagation of SAWs on the stone boundary is accompanied by a progressive transition of the LSW reflection pattern from regular to von Neumann and to weak von Neumann reflection near the glancing incidence and, concomitantly, the development and growth of a Mach stem, swirling around the stone boundary. The maximum tensile stress and stress integral were produced by SAWs on the stone boundary under asymmetric loading conditions, which drove the initiation and extension of surface cracks into the bulk of the stone that is confirmed by micro-computed tomography analysis.

Boosting Zinc-Ion Storage Capability by Effectively Suppressing Vanadium Dissolution Based on Robust Layered Barium Vanadate.

Vanadium-based compounds with an open framework structure have become the subject of much recent investigation into aqueous zinc-ion batteries (AZIBs) due to high specific capacity. However, there are some issues with vanadium dissolution from a cathode framework as well as the generation of byproducts during discharge that should not be ignored, which could cause severe capacity deterioration and inadequate cycle life. Herein, we report several barium vanadate nanobelt cathodes constructed of two sorts of architectures, i.e., Ba1.2V6O16·3H2O and BaV6O16·3H2O (V3O8-type) and BaxV2O5·nH2O (V2O5-type), which are controllably synthesized by tuning the amount of barium precursor. Benefiting from the robust architecture, layered BaxV3O8-type nanobelts (Ba1.2V6O16·3H2O) exhibit superior rate capability and long-term cyclability owing to fast zinc-ion kinetics, enabled by efficiently suppressing cathode dissolution as well as greatly eliminating the generation of byproduct Zn4SO4(OH)6·xH2O, which provides a reasonable strategy to engineer cathode materials with robust architectures to improve the electrochemical performance of AZIBs.

Hierarchical Octahedra Constructed by Cu2 S/MoS2 ⊂Carbon Framework with Enhanced Sodium Storage.

Metal sulfides have aroused considerable attention for efficient sodium storage because of their high capacity and decent redox reversibility. However, the poor rate capability and fast capacity decay greatly hinder their practical application in sodium-ion batteries. Herein, a self-template-based strategy is designed to controllably synthesize hierarchical microoctahedra assembled with Cu2 S/MoS2 heterojunction nanosheets in the porous carbon framework (Cu2 S/MoS2 ⊂PCF) via a facile coprecipitation method coupled with vulcanization treatment. The Cu2 S/MoS2 ⊂PCF microoctahedra with 2D hybrid nanosubunits reasonably integrate several merits including facilitating the diffusion of electrons and Na+ ions, enhancing the electric conductivity, accelerating the ion and charge transfer, and buffering the volume variation. Therefore, the Cu2 S/MoS2 ⊂PCF composite manifests efficient sodium storage performance with high capacity, long cycling life, and excellent rate capability.

Boosting Na+ Storage Ability of Bimetallic Mox W1-x Se2 with Expanded Interlayers.

In spite of the valuable advancements in the fabrication of transition-metal selenides (TMSs)-based hybrid structures, only single-metal selenides have been obtained through most of the present methods. Herein, a facile room-temperature self-polymerization and subsequent selenization strategy is proposed for the synthesis of bimetallic Mox W1-x Se2 nanosheets with expanded interlayers decorated with N-doped carbon-matrix assembled flowerlike hierarchical microspheres (Mox W1-x Se2 /NC). Depending on the excellent coordination ability of dopamine with metal ions, self-formed flowerlike single precursors are harvested. The unique hybrid architecture benefits the penetration of the electrolyte, accelerates Na+ insertion/extraction kinetics, enhances electron-transfer ability, and alleviates the volume expansion and aggregation during cycling processes. Therefore, the bimetallic Mox W1-x Se2 /NC electrode delivers high reversible capacities of 264 mA h g-1 at 1 A g-1 for 700 cycles, 204.4 mA h g-1 at 4 A g-1 for 1400 cycles, and 153.3 mA h g-1 at 8 A g-1 for 2000 cycles, as well as an excellent rate capability up to 10 A g-1 with a capacity of 188.9 mA h g-1 . Our study offers an effective strategy to boost sodium storage performance through elaborate structural engineering.

Metal-Organic Frameworks-Derived Mesoporous Si/SiOx @NC Nanospheres as a Long-Lifespan Anode Material for Lithium-Ion Batteries.

Silicon (Si)-based anode materials with suitable engineered nanostructures generally have improved lithium storage capabilities, which provide great promise for the electrochemical performance in lithium-ion batteries (LIBs). Herein, a metal-organic framework (MOF)-derived unique core-shell Si/SiOx @NC structure has been synthesized by a facile magnesio-thermic reduction, in which the Si and SiOx matrix were encapsulated by nitrogen (N)-doped carbon. Importantly, the well-designed nanostructure has enough space to accommodate the volume change during the lithiation/delithiation process. The conductive porous N-doped carbon was optimized through direct carbonization and reduction of SiO2 into Si/SiOx simultaneously. Benefiting from the core-shell structure, the synthesized product exhibited enhanced electrochemical performance as an anode material in LIBs. Particularly, the Si/SiOx @NC-650 anode showed the best reversible capacities up to 724 and 702 mAh g-1 even after 100 cycles. The excellent cycling stability of Si/SiOx @NC-650 may be attributed to the core-shell structure as well as the synergistic effect between the Si/SiOx and MOF-derived N-doped carbon.

Expression, purification and identification of a thermolysin-like protease, neutral protease I, from Aspergillus oryzae with the Pichia pastoris expression system.

Neutral proteases are widely used in the textile, food and medical industries. This study was designed to obtain high expression levels of neutral protease I from Aspergillus oryzae 3.042 by using Pichia pastoris GS115 as the host strain for industrial purposes. The coding sequence of the target gene was modified, synthesized, and then cloned into the expression vector pHBM905BDM, which harbored the d1+2 × 201 AOX1 promoter and the MF4I leader sequence. The recombinant plasmid was transformed into Pichia pastoris GS115. The recombinant strain was used for high-density fermentation in a 4-L fermenter. The yield of the target protein reached 12.87 mg/mL, and the enzyme activity was approximately 49370 U/mL, which indicated that this enzyme was expressed in Pichia pastoris at a high level. The target protein was purified and characterized. Its optimum temperature and pH were 55 °C and 8.0, respectively. This enzyme was extremely sensitive to EDTA, which is consistent with the previous reports that it is a zinc-dependent metalloprotease. Our results indicated that low concentrations of zinc, calcium and magnesium ions stimulated the enzyme activity, whereas high concentrations inhibited its activity. In addition, calcium and magnesium ions increased the thermostability of the enzyme. All of the evidence indicated that this protease is a thermolysin-like peptidase.

High-level expression of Proteinase K from Tritirachium album Limber in Pichia pastoris using multi-copy expression strains.

Proteinase K is widely used in scientific research and industries. This report was aimed to achieve high-level expression of proteinase K using Pichia pastoris GS115 as the host strain. The coding sequence of a variant of proteinase K that has higher activity than the wild type protein was chosen and optimized based on the codon usage preference of P. pastoris. The novel open reading frame was synthesized and a series of multi-copy expression vectors were constructed based on the pHBM905BDM plasmid, allowing for the tandem integration of multiple copies of the target gene into the genome of P. pastoris with a single recombination. These strains were used to study the correlation between the gene copy number and the expression level of proteinase K. The results of quantitative polymerase chain reaction (qPCR) indicated that the tandem expression cassettes were integrated into the host genome stably. Meanwhile, the results of qPCR and enzyme activity assays indicated that the mRNA and protein expression levels of the target gene increased as the gene copy number increased. Moreover, the effect of gene dosage on the expression level of the recombinant protein was more obvious using high-density fermentation. The maximum expression level and enzyme activity of proteinase K, which were obtained from the recombinant yeast strain bearing 5 copies of the target gene after an 84-h induction, were approximately 8.069 mg/mL and 108,295 U/mL, respectively. The recombinant proteinase was purified and characterized. The optimum pH and temperature for the activity of this protease were approximately pH 11 and 55 °C, respectively.

Surface Engineering on Zinc Anode for Aqueous Zinc Metal Batteries.

Rechargeable aqueous zinc metal batteries (AZMBs) are considered as a potential alternative to lithium-ion batteries due to their low cost, high safety, and environmental friendliness. However, the Zn anodes in AZMBs face severe challenges, such as dendrite growth, metal corrosion, and hydrogen evolution, all of which are closely related to the Zn/electrolyte interface. This article offers a short review on surface passivation to alleviate the issues on the Zn anodes. The composition and structure of the surface layers significantly influence their functions and then the performance of the Zn anodes. The recent progresses are introduced, according to the chemical components of the passivation layers on the Zn anodes. Moreover, the challenges and prospects of surface passivation in stabilizing Zn anodes are discussed, providing valuable guidance for the development of AZMBs.

Zn(002)-preferred and pH-buffering triethanolamine as electrolyte additive for dendrite-free Zn anodes.

Zn anodes of aqueous batteries face severe challenges from side reactions and dendrite growth. Here, triethanolamine (TEOA) is developed as an electrolyte additive to address these challenges. It enhances the exposure of Zn(002) and diminishes the change in pH. Therefore, the electrolyte containing TEOA shows improved electrochemical performance.

Revealing the Na storage behavior of graphite anodes in low-concentration imidazole-based electrolytes.

The thermodynamic instability of Na+-intercalated compounds is an important factor limiting the application of graphite anodes in sodium-ion batteries. Although solvent co-intercalation is recognized as a simple and effective strategy, the challenge lies in the lack of durable electrolytes. Herein, we successfully apply low-concentration imidazole-based electrolytes to graphite anodes for sodium-ion batteries. Specifically, low concentrations ensure high ionic conductivity while saving on costs. Methylimidazole molecules can be co-intercalated with Na+, and a small amount of unreleased solvated Na+ serves the dual purpose of providing support to the graphite layer and preventing peeling off. The interphase formed in imidazole is more uniform and dense compared with that in ether electrolytes, which reduces side reactions and the risk of internal short circuits. The obtained battery demonstrates a long cycle life of 1800 cycles with a capacity retention of 84.6%. This success extends to other imidazole-based solvents such as 1-propylimidazole and 1-butylimidazole.

Iodine assisted low temperature synthesis of 3C-SiC nanostructures and their formation process.

3C-SiC nanostructures have been synthesized from Si, maltose or glucose and Mg at 120 degrees C in the presence of I2. The as-obtained products are the mixtures of wire-like and tower-shaped SiC nanostructures. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) images show that wire-like nanostructures are formed by the leaning-type packing of triangular nanosheets with the average diameter of 60 nm and tower-shaped nanostructures are formed by the level-type packing of nanosheets with the average diameter of 750 nm and thickness of about 40 nm. The effects of iodine, reaction time and temperature on the morphologies of the final products were also discussed.

Effect of Jiuwei Zhuhuang Powder on Cough Resolution in Children with Upper Respiratory Tract Infections: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of Jiuwei Zhuhuang Powder (JWZH), a Tibetan patent medicine in treating upper respiratory tract infection (URTI) associated cough in children. METHODS: The study was a multicenter, randomized, open-label, controlled trial. A total of 142 children aged 2 to 14 years old, with URTI-associated cough within 48 h of onset, were randomly assigned to two groups at a 1:1 ratio by computer-generated randomization sequence. Children were treated with JWZH (1 to 1.5 g, twice to thrice daily) in the treatment group or conventional treatment (Pediatric Paracetamol, Artificial Cow-bezoar and Chlorphenamine Maleate Granules, 0.25 to 1 g, thrice daily) in the control group for 5 days. The primary endpoints were the time to cough resolution and 4-day cough resolution rate. The secondary endpoints were the daily improvement in symptom scores and cough resolution rate during the study period. RESULTS: A total of 138 children were included in the intention-to-treat analysis, with 71 cases in the treatment group and 67 cases in the control group. Compared with the conventional treatment, the children receiving JWZH had a shorter time to cough resolution [hazard ratio, 2.10; 95% confidence interval (CI), 1.29-3.40; P=0.003]. The median time to cough resolution for children receiving JWZH was shorter than that of the conventional treatment (2 days vs. 3 days; P<0.001). The 4-day cough resolution rate in the JWZH group was higher than that of the control group (94.4% vs. 74.6%; risk difference: 19.8%, 95% CI: 8.1%-31.5%; relative risk: 1.265, 95% CI: 1.088-1.470; P=0.001). There were no statistically significant differences in the improvement of other symptoms caused by URTI (P>0.05). Adverse events was reported in 5.6% (4/71) and 4.5% (3/67) in participants of JWZH and PPACCM groups (P>0.05), respectively, which were all mild and resolved without treatment. CONCLUSION: JWZH seemed to be a safe and effective therapy for URTI-associated cough in children. (Trial registration No. ChiCTR2000039421).