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In response to the problem of low hardness and poor wear resistance of TC4 coatings prepared by laser additive manufacturing, three titanium alloy coatings with different Si contents were prepared on a TC4 substrate by direct laser deposition (DLD) technology. The evolution of the microstructure and wear mechanism of the coatings were studied. The addition of the Si element facilitated the formation of Ti5Si3 hard phase, which exhibited a uniform mesh form. The strengthening effect of the hard phase in the prepared coating increased with its proportion, demonstrating a positive correlation with the incremental addition of an Si element. However, the excessive addition of the Si element resulted in the surface cracking of the coating. The optimal DLD Ti-Al-Si coating was obtained when the Si content was 10 wt. %, with an average microhardness of 801 ± 24 HV0.2, 2.5 times greater than that of the TC4 substrate. The average friction coefficient of the Ti-Al-Si coating was 0.39, and the wear rate was 1.9%. The hard phase was uniformly distributed in a mesh form, which not only refined the wear debris and suppressed the shear force of the wear debris during wear but also slowed down the continuous wear of debris on the worn surface. The results of this study could provide a reference for preparing high-hardness and wear-resistant titanium alloy coatings by DLD. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients. [ABSTRACT FROM AUTHOR]

Intumescent flame retardants (IFRs) are mainly composed of ammonium polyphosphate (APP), melamine (ME), and some macromolecular char-forming agents. The traditional IFR still has some defects in practical application, such as poor compatibility with the matrix and low flame-retardant efficiency. In order to explore the best balance between flame retardancy and mechanical properties of flame-retardant polyformaldehyde (POM) composite, a biobased calcium magnesium bi-ionic melamine phytate (DPM) synergist was prepared based on renewable biomass polyphosphate phytic acid (PA), and its synergistic system with IFRs was applied to an intumescent flame-retardant POM system. POM/IFR systems can only pass the V-1 grade of the vertical combustion test (UL-94) if they have a limited oxygen index (LOI) of only 48.5%. When part of an IFR was replaced by DPM, the flame retardancy of the composite was significantly improved, and the POM/IFR/4 wt%DPM system reached the V-0 grade of UL-94, and the LOI reached 59.1%. Compared with pure POM, the PkHRR and THR of the POM/IFR/4 wt%DPM system decreased by 61.5% and 51.2%, respectively. Compared with the POM/IFR system, the PkHRR and THR of the POM/IFR/4 wt%DPM system were decreased by 20.8% and 27.5%, respectively, and carbon residue was increased by 37.2%. The mechanical properties of the composite also showed a continuous upward trend with the increase in DPM introduction. It is shown that the introduction of DPM not only greatly reduces the heat release rate and heat release amount of the intumescent flame-retardant POM system, reducing the fire hazard, but it also effectively improves the compatibility between the filler and the matrix and improves the mechanical properties of the composite. It provides a new approach for developing a new single-component multifunctional flame retardant or synergist for intumescent flame-retardant POM systems. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP) and is associated with increased morbidity and mortality. Objective: This study aimed to establish and validate predictive models for AKI in hospitalized patients with CAP based on machine learning algorithms. Methods: We trained and externally validated 5 machine learning algorithms, including logistic regression, support vector machine, random forest, extreme gradient boosting, and deep forest (DF). Feature selection was conducted using the sliding window forward feature selection technique. Shapley additive explanations and local interpretable model-agnostic explanation techniques were applied to the optimal model for visual interpretation. Results: A total of 6371 patients with CAP met the inclusion criteria. The development of CAP-associated AKI (CAP-AKI) was recognized in 1006 (15.8%) patients. The 11 selected indicators were sex, temperature, breathing rate, diastolic blood pressure, C-reactive protein, albumin, white blood cell, hemoglobin, platelet, blood urea nitrogen, and neutrophil count. The DF model achieved the best area under the receiver operating characteristic curve (AUC) and accuracy in the internal (AUC=0.89, accuracy=0.90) and external validation sets (AUC=0.87, accuracy=0.83). Furthermore, the DF model had the best calibration among all models. In addition, a web-based prediction platform was developed to predict CAP-AKI. Conclusions: The model described in this study is the first multicenter-validated AKI prediction model that accurately predicts CAP-AKI during hospitalization. The web-based prediction platform embedded with the DF model serves as a user-friendly tool for early identification of high-risk patients. [ABSTRACT FROM AUTHOR]

Drosophila sodium channel 1 (DSC1) encodes a voltage‐gated divalent cation channel that mediates neuronal excitability in insects. Previous research revealed that DSC1 knockout Drosophila melanogaster conferred different susceptibility to insecticides, which indicated the vital regulation role of DSC1 under insecticide stress. Haedoxan A (HA) is a lignan compound isolated from Phryma leptostachya, and we found that HA has excellent insecticidal activity and is worthy of further study as a botanical insecticide. Herein, we performed bioassay and electrophysiological experiments to test the biological and neural changes in the larval Drosophila with/without DSC1 knockout in response to HA. Bioassay results showed that knockout of DSC1 reduced the sensitivity to HA in both w1118 (a common wild‐type strain in the laboratory) and parats1 (a pyrethroid‐resistant strain) larvae. Except for parats1/DSC1−/−, electrophysiology results implicated that HA delayed the decay rate and increased the frequency of miniature excitatory junctional potentials of Drosophila from w1118, parats1, and DSC1−/− strains. Moreover, the neuromuscular synapse excitatory activities of parats1/DSC1−/− larvae were more sensitive to HA than DSC1−/− larvae, which further confirmed the functional contribution of DSC1 to neuronal excitability. Collectively, these results indicated that the DSC1 channel not only regulated the insecticidal activity of HA, but also maintained the stability of neural circuits through functional interaction with voltage‐gated sodium channels. Therefore, our study provides useful information for elucidating the regulatory mechanism of DSC1 in the neural system of insects involving the action of HA derived from P. leptostachya. [ABSTRACT FROM AUTHOR]