MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD-associated NSCLC.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response. METHODS: Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti-programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5-OP-RU using a mouse subcutaneous tumor model. RESULTS: Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5-OP-RU enhanced the antitumor effects of anti-PD1. CONCLUSIONS: In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

Self-Healing Conjugated Microporous Polyanilines for Effective and Continuous Catalytic Detoxification of 4-Nitrophenol to 4-Aminophenol.

Detoxification of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with high efficiency and dynamic performance is challenging for a polymeric catalyst. Herein, a series of conjugated microporous polyanilines (CMPAs), capable of efficiently catalytically reducing 4-NP, were synthesized based on the Buchwald-Hartwig cross-coupling reaction mechanism. By adjusting the types of linkers and the molar ratios of linker to core, CMPAs with different Brunauer-Emmett-Teller (BET) specific surface areas and reduction degrees were obtained and used as the catalysts in reducing 4-NP. The ultrahigh catalytic reduction efficiency (K = 141.32 s-1 g-1, kapp = 0.00353 s-1) was achieved when using CMPA-3-0.7 as the catalyst (prepared with 4,4'-diaminodiphenylamine as the linker and a 0.7:1 molar ratio of linker to core). The catalytic reduction performance exhibited a strong correlation with the reduction degree and BET specific surface area of CMPAs. Furthermore, they also exhibit excellent cycling stability and dynamic performance. The coexistence of a microporous structure and high BET specific surface area endowed CMPAs with an increased number of catalytic active centers. The reversible redox transformation of CMPAs in the presence of NaBH4 and air enabled self-healing (the oxidation units in CMPAs were reduced to reduction units by NaBH4, and the newly generated reduction unit in CMPAs was subsequently oxidized to its original state by the O2 in the air), leading to the reduction reaction of 4-NP proceeded continuously and stably. The aforementioned factors resulted in the high efficiency of CMPAs for reducing 4-NP to 4-AP, enhancing the practical application prospects of CMPAs in the detoxification of 4-NP wastewater.

Investigating the Dynamic Mechanical Properties and Strengthening Mechanisms of Ti-6Al-4V Alloy by Using the Ultrasonic Surface Rolling Process.

The demand for titanium alloy has been increasing in various industries, including aerospace, marine, and biomedical fields, as they fulfilled the need for lightweight, high-strength, and corrosion-resistant material for modern manufacturing. However, titanium alloy has relatively low hardness, poor wear performance, and fatigue properties, which limits its popularization and application. These disadvantages could be efficiently overcome by surface strengthening technology, such as the ultrasonic surface rolling process (USRP). In this study, the true thermo-mechanical deformation behavior of Ti-6Al-4V was obtained by dynamic mechanical experiment using a Hopkinson pressure bar. Moreover, USRP was applied on the Ti-6Al-4V workpiece with different parameters of static forces to investigate the evolution in surface morphology, surface roughness, microstructure, hardness, residual stress, and fatigue performance. The strain rate and temperature during the USRP of Ti-6Al-4V under the corresponding conditions were about 3000 s-1 and 200 °C, respectively, which were derived from the numerical simulation. The correlation between the true thermo-mechanical behavior of Ti-6Al-4V alloy and the USRP parameters of the Ti-6Al-4V workpiece was established, which could provide a theoretical contribution to the optimization of the USRP parameters. After USRP, the cross-sectional hardness distribution of the workpiece was shown to initially rise, followed by a subsequent decrease, ultimately to matrix hardness. The cross-sectional residual compressive stress distribution of the workpiece showed a tendency to initially reduce, then increase, and finally decrease to zero. The fatigue performance of the workpiece was greatly enhanced after USRP due to the effect of grain refinement, work hardening, and beneficial residual compressive stress, thereby inhibiting the propagation of the fatigue crack. However, it could be noted that the excessive static force parameter of USRP could induce the decline in surface finish and compressive residual stress of the workpiece, which eliminated the beneficial effect of the USRP treatment. This indicated that the choice of the optimal USRP parameters was highly crucial. This work would be conducive to achieving high-efficiency and low-damage USRP machining, which could be used to effectively guide the development of high-end equipment manufacturing.

Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. PATIENTS AND METHODS: Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy's effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. RESULTS: A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295-4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV-H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). CONCLUSIONS: The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. TRIAL REGISTRATION: Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

Effect of magnetic nano-particles combined with multi-frequency ultrasound-assisted thawing on the quality and myofibrillar protein-related properties of salmon (Salmo salar).

Multi-frequency ultrasound-assisted thawing (MUAT) has been proven to be an effective method of maintaining the quality of frozen food. The effects of magnetic nano-particles (MNPs) combined with MUAT and multi-frequency ultrasound-assisted sequential thawing (MUST) on water retention, myofibrillar protein (MP) structural characteristics, function characteristics, and MP aggregation and degradation of salmon (Salmo salar) were studied. The results showed that MNPs combined with multi-frequency ultrasound-assisted sequential thawing (MNPs-MUST) significantly improved the thawing rate and the retention of water and had better emulsifying and foaming properties. MNPs-MUST treatment reduced the oxidation and degradation of MP, increased sulfhydryl content, and protected the structure of MP. Confocal laser scanning microscopy (CLSM) indicated that the MP transformed into a filamentous polymer into more evenly distributed units, resulting in higher protein solubility, lower surface hydrophobicity, and lower protein turbidity. Therefore, MNPs combined with MUST has a potential application value in the thawing research of frozen salmon.

Accurate Clinical Detection of Vitamin D by Mass Spectrometry: A Review.

Vitamin D deficiency is thought to be associated with a wide range of diseases, including diabetes, cancer, depression, neurodegenerative diseases, and cardiovascular and cerebrovascular diseases. This vitamin D deficiency is a global epidemic affecting both developing and developed countries and therefore qualitative and quantitative analysis of vitamin D in a clinical context is essential. Mass spectrometry has played an increasingly important role in the clinical analysis of vitamin D because of its accuracy, sensitivity, specificity, and the ability to detect multiple substances at the same time. Despite their many advantages, mass spectrometry-based methods are not without analytical challenges. Front-end and back-end challenges such as protein precipitation, analyte extraction, derivatization, mass spectrometer functionality, must be carefully considered to provide accurate and robust analysis of vitamin D through a well-designed approach with continuous control by internal and external quality control. Therefore, the aim of this review is to provide a comprehensive overview of the development of mass spectrometry methods for vitamin D accurate analysis, including emphasis on status markers, deleterious effects of biological matrices, derivatization reactions, effects of ionization sources, contribution of epimers, standardization of assays between laboratories.

Electrocatalysis coupled heterogeneous electro-Fenton like treatment of coal gasification wastewater using tourmaline as catalyst: process parameters and response surface.

Coal gasification technology is essential for realizing clean and efficient conversion of coal, as well as for reducing carbon emissions. However, coal gasification technology is accompanied by a large amount of coal gasification wastewater that is biodegradable. In this work, tourmaline was applied as a catalyst in electro-Fenton like process for treating coal gasification wastewater. The optimal applied parameters of coal gasification wastewater were investigated as follows: current density of 90 mA cm-2, tourmaline dosage of 8 g L-1, electrode gap of 1 cm, and temperature at 25 °C; the COD removal ratio reached 91.24% after 240-min treatment. In addition, the current density and tourmaline dosage were further optimized by response surface method. The result was about current density with 82.4 mA cm-2 and catalyst with 7.57 g L-1; the predicted COD removal efficiency was 86.91%. Under the optimal parameters the actual COD removal efficiency was 88.25% a little high than the predicted value. To explore the reusability of tourmaline as Fenton reaction catalyst, five cycles of experiments were carried out. The result demonstrated that tourmaline could be used as catalyst for treating coal gasification wastewater by electro-Fenton like process.

Shape-Regulated Photothermal-Catalytic Tumor Therapy Using Polydopamine@Pt Nanozymes with the Elicitation of an Immune Response.

Recently, nanozyme-based photothermal-catalytic therapy has emerged as a promising strategy for antitumor treatment. Extensive research has focused on optimizing the catalytic activity and photothermal conversion performance of nanozymes through size, morphology, and surface property regulations. However, the biological effects of nanozymes, such as cellular uptake and cytotoxicity, resulting from their physicochemical properties, remain largely unexplored. In this study, two types of polydopamine/platinum (PDA@Pt) nanozymes, flower-like (FPDA@Pt) and mesoporous spherical-like (MPDA@Pt), to comprehensively compare their enzyme-mimicking activity, photothermal conversion capacity, and antitumor efficiency are designed. These findings revealed that FPDA@Pt exhibited superior peroxidase-like activity and higher photothermal conversion efficiency compared to MPDA@Pt. This led to enhanced production of reactive oxygen species (ROS) and increased heat generation at tumor sites. Importantly, it is observed thatthe flower-like structure of FPDA@Pt facilitated enhanced cellular uptake, leading to an increased accumulation of nanozymes within tumor cells. Furthermore, the light irradiation on tumors also triggered a series of anti-tumor immune responses, further enhancing the therapeutic efficacy. This work provides a possible design orientation for nanozyme-based photothermal-catalytic tumor therapy, highlighting the importance of considering the physicochemical properties of nanozymes to optimize their therapeutic potential in antitumor strategies.

Mass Spectrometry Analysis for Clinical Applications: A Review.

Mass spectrometry (MS) has become an attractive analytical method in clinical analysis due to its comprehensive advantages of high sensitivity, high specificity and high throughput. Separation techniques coupled MS detection (e.g., LC-MS/MS) have shown unique advantages over immunoassay and have developed as golden criterion for many clinical applications. This review summarizes the characteristics and applications of MS, and emphasizes the high efficiency of MS in clinical research. In addition, this review also put forward further prospects for the future of mass spectrometry technology, including the introduction of miniature MS instruments, point-of-care detection and high-throughput analysis, to achieve better development of MS technology in various fields of clinical application. Moreover, as ambient ionization mass spectrometry (AIMS) requires little or no sample pretreatment and improves the flux of MS, this review also summarizes its potential applications in clinic.

A Micro-Topography Measurement and Compensation Method for the Key Component Surface Based on White-Light Interferometry.

The grinding grooves of material removal machining and the residues of a machining tool on the key component surface cause surface stress concentration. Thus, it is critical to carry out precise measurements on the key component surface to evaluate the stress concentration. Based on white-light interferometry (WLI), we studied the measurement distortion caused by the reflected light from the steep side of the grinding groove being unable to return to the optical system for imaging. A threshold value was set to eliminate the distorted measurement points, and the cubic spline algorithm was used to interpolate the eliminated points for compensation. The compensation result agrees well with the atomic force microscope (AFM) measurement result. However, for residues on the surface, a practical method was established to obtain a microscopic 3D micro-topography point cloud and a super-depth-of-field fusion image simultaneously. Afterward, the semantic segmentation network U-net was adopted to identify the residues in the super-depth-of-field fusion image and achieved a recognition accuracy of 91.06% for residual identification. Residual feature information, including height, position, and size, was obtained by integrating the information from point clouds and super-depth-of-field fusion images. This work can provide foundational data to study surface stress concentration.

Recent Advances in Catecholamines Analytical Detection Methods and Their Pretreatment Technologies.

Catecholamines (CAs), including adrenaline, noradrenaline, and dopamine, are neurotransmitters and hormones that play a critical role in regulating the cardiovascular system, metabolism, and stress response in the human body. As promising methods for real-time monitoring of catecholamine neurotransmitters, LC-MS detectors have gained widespread acceptance and shown significant progress over the past few years. Other detection methods such as fluorescence detection, colorimetric assays, surface-enhanced Raman spectroscopy, and surface plasmon resonance spectroscopy have also been developed to varying degrees. In addition, efficient pretreatment technology for CAs is flourishing due to the increasing development of many highly selective and recoverable materials. There are a few articles that provide an overview of electrochemical detection and efficient enrichment, but a comprehensive summary focusing on analytical detection technology is lacking. Thus, this review provides a comprehensive summary of recent analytical detection technology research on CAs published between 2017 and 2022. The advantages and limitations of relevant methods including efficient pretreatment technologies for biological matrices and analytical methods used in combination with pretreatment technology have been discussed. Overall, this review article provides a better understanding of the importance of accurate CAs measurement and offers perspectives on the development of novel methods for disease diagnosis and research in this field.

Synthesis of Ti3C2T x /MnO2 composites for synergistic catalytic/photothermal-based bacterial inhibition.

Human inflammation caused by bacterial infection threatens global public health. The abuse of antibiotics often leads to the development of drug resistance in bacteria. To address this issue, nanozymes with peroxidase-like (POD-like) activity have often been reported for bacteriostasis with the assistance of catalytic substrate hydrogen peroxide (H2O2). However, it is difficult to achieve efficient bactericidal outcomes only through exertion of the POD-like activity of nanozymes. Here, MnO2 loaded Ti3C2T x (Ti3C2T x /MnO2) was prepared by a two-step reaction method, in which MnO2 showed high oxidase-like (OXD-like) activity to elevate the levels of reactive oxygen species (ROS) without H2O2 and Ti3C2T x exhibited high photothermal conversion efficiency to induce hyperthermia. Thus, the obtained Ti3C2T x /MnO2 realized synergistic catalytic/photothermal-based bacterial inhibition, including for Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and methicillin-resistant Staphylococcus aureus. Importantly, Ti3C2T x /MnO2 with near-infrared light irradiation successfully promoted Staphylococcus aureus-infected wound healing in mouse models, representing an alternative treatment to fight against bacterial infection.

Anti-corrosive non-aqueous DBSA/MEA lamellar liquid crystal lubrication system.

HYPOTHESIS: Since lamellar liquid crystals (LLCS) could be used for lubrication, many LLCS systems have been constructed to improve lubrication performance. However, most studies focused on the LLCS of the water system, and its corrosiveness brought some limitations to its application. Therefore, it is necessary to construct a non-aqueous LLCS system with good lubrication and anti-corrosion properties to improve its applicability. EXPERIMENTS: Anionic surfactant dodecyl benzene sulfonic acid (DBSA) was used to construct non-aqueous LLCS in different solvents, including monoethanolamine (MEA) and diethanolamine (DEA). DBSA/H2O LLCS system was constructed for comparison. The LLCS was characterized by polarizing microscope (POM), small-angle X-ray scattering (SAXS), and rheology. Its microstructure was discussed. Meanwhile, we evaluated the lubrication and anti-corrosion performance of LLCS. Its lubrication mechanism was explained through tribology tests and X-ray photoelectron spectrometer (XPS) analysis of the wear scar surface. Its anti-corrosion mechanism was investigated by using the weightlessness method, electrochemical test method, and quantum chemical theoretical calculations. FINDINGS: The DBSA/MEA non-aqueous LLCS system showed better lubrication performance than DBSA/DEA and DBSA/H2O LLCS. It can adsorb on the surface of the friction pair to form a lubrication friction film, which plays a better role in reducing friction and wear. The DBSA/MEA LLCS is less corrosive to metals because it can effectively isolate oxygen and water in the air between friction pairs. Furthermore, the lone pair electrons in the 2p orbital of the N atom in the MEA molecule could coordinate with the 3d empty orbital of the Fe atom, forming a protective film on the metal surface, which plays a good anti-corrosion effect. This work not only enriched the study of non-aqueous LLCS but also expanded its potential applications in the field of lubrication.

CaCO3-assistant synthesis of pH/near-infrared light-responsive and injectable sodium alginate hydrogels for melanoma synergistic treatment.

Melanoma is an aggressive tumor located in skin with high rates of recurrence and metastasis. Due to the limited traditional therapies, the development of novel strategies against melanoma is urgently quested. To reduce the side effects of traditional administration ways and amplify the killing effect, an injectable sodium alginate (SA)-based hydrogels were developed, in which CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) were embedded for the synergistic photothermal/calcium ions interference therapy of melanoma. In the study, the formation conditions and mechanical properties of CaCO3/PDA-SA hydrogels were characterized, and their antitumor efficiency and mechanism against mouse melanoma cells were investigated. Wheninjectedintratumorally, CaCO3/PDA-SA fluid was converted into hydrogel in situ through the interaction of pH-sensitive released Ca2+ and alginate chains, which increased the retention time of photothermal agents (CaCO3/PDA NPs) at tumor sites and thereby was more conducive to produce hyperthermia via photothermal conversion to combat melanoma. Moreover, in acidic tumor microenvironment, the residual CaCO3/PDA NPs in hydrogels continuously decomposed and released Ca2+ to destroy the Ca2+ buffering capacity and evoke the mitochondrial Ca2+-overloading, resulting in the inhibition of adenosine triphosphate production to accelerate cell death. Notably, besides the heat elevation, the near-infrared light (NIR) irradiation would further enhance the release of Ca2+ to promote the Ca2+-involved cell death. Therefore, a pH/NIR-responsive and injectable SA-based hydrogels were successfully established and showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.

Stress Distribution in Wear Analysis of Nano-Y2O3 Dispersion Strengthened Ni-Based µm-WC Composite Material Laser Coating.

Oxide-dispersion- and hard-particle-strengthened (ODS) laser-cladded single-layer multi-tracks with a Ni-based alloy composition with 20 wt.% µm-WC particles and 1.2 wt.% nano-Y2O3 addition were produced on ultra-high-strength steel in this study. The investigation of the composite coating designed in this study focused on the reciprocating friction and wear workpiece surface under heavy load conditions. The coating specimens were divided into four groups: (i) Ni-based alloy, nano-Y2O3, and 2 µm-WC (2 µm WC-Y/Ni); (ii) Ni-based alloy with added 2 µm-WC (2 µmWC/Ni); (iii) Ni-based alloy with added 80 µm-WC (80 µmWC/Ni); and (iv) base metal ultra-high-strength alloy steel 30CrMnSiNi2A. Four conclusions were reached: (1) Nano-Y2O3 could effectively inhibit the dissolution of 2 µm-WC. (2) It can be seen from the semi-space dimensionless simulation results that the von Mises stress distribution of the metal laser composite coating prepared with a 2 µm-WC particle additive was very uniform and it had better resistance to normal impact and tangential loads than the laser coating prepared with the 80 µm-WC particle additive. (3) The inherent WC initial crack and dense stress concentration in the 80 µm-WC laser coating could easily cause dislocations to accumulate, as shown both quantitatively and qualitatively, resulting in the formation of micro-crack nucleation. After the end of the running-in phase, the COF of the 2 µm-WC-Y2O3/Ni component samples stabilized at the minimum of the COF of the four samples. The numerical order of the four COF curves was stable from small to large as follows: 2 µm-WC-Y2O3/Ni, 2 µm-WC/Ni, 80 µm-WC/Ni, and 30CrMnSiNi2A. (4) The frictional volume loss rate of 2 µm-WC-Y2O3/Ni was 1.3, which was significantly lower than the corresponding values of the other three components: 2.4, 3.5, and 13.

Yolk-shell Fe3O4@Carbon@Platinum-Chlorin e6 nanozyme for MRI-assisted synergistic catalytic-photodynamic-photothermal tumor therapy.

HYPOTHESIS: Tumor treatments based on phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), are promising anticancer strategies. However, their dependence on light also poses several limitations for their application. Therefore, the establishment of a multifunctional nanotheranostic platform based on light therapy is needed to improve applicability of the technology. EXPERIMENTS: We designed yolk-shell magnetic Fe3O4@Carbon@Platinum-Chlorin e6 nanoparticles (MCPtCe6), which may be used for Magnetic resonance imaging (MRI) and synergistic catalytic-photodynamic-photothermal (catalytic-PDT-PTT) tumor therapy. FINDINGS: We designed to compound multiple nanozymes and solve the drawbacks of single nanozyme and give additional functionalization to nanozymes for tumor therapy. Fe3O4 has T2 weighted MRI ability. The designed yolk-shell structure can disperse Fe3O4 in the carbon shell layer, which in turn can act as a carrier for PtNPs and improve the dispersion of both Fe3O4 and Pt. Pt nanoparticles attached to the surface of N-doped carbon spheres enhanced the catalytic ability of the nanozyme to generate reactive oxygen species (ROS). The covalently linked photosensitizer chlorin e6 (Ce6) on the Fe3O4@C@Pt (MCPt) nanozyme is essential for the therapeutic effects of PDT. MCPtCe6 can be specifically activated by the microenvironment through an enzyme-like catalytic process and extend PDT/PTT in acidic and H2O2-rich microenvironments. The results showed that MCPtCe6 had a high photothermal conversion efficiency (η = 28.28%), indicating its feasibility for PTT. Further cellular and animal studies have revealed that catalytic-PDT-PTT therapy can effectively inhibit tumors both in vitro and in vivo.

Construction of core-in-shell Au@N-HCNs nanozymes for tumor therapy.

Noble metals act as nanozymes that can generate reactive oxygen species (ROS) by catalysis to induce apoptosis of tumor cells for cancer therapy. But they are easy to aggregate, which will affect their further application. Carbon materials are often used as the carrier of noble metals to improve their catalytic performance. However, designing a composite structure to build an efficient carbon/noble metal hybrid nanozyme with high catalytic performance for tumor therapy is still a significant challenge. In this work, a core-in-shell structure nanozyme composed of gold nanoparticles (AuNPs) embedded in nitrogen-doped hollow carbon nanoshells (AuNPs@N-HCNs) were fabricated, which exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) activity. Compared with core-out-of-shell structure composite, the AuNPs@N-HCNs showed a better ability to generate ROS to kill tumor cells. Furthermore, AuNPs@N-HCNs also exhibited satisfactory photothermal conversion properties, which helped build a platform for photothermal therapy. Meanwhile, the enzyme activity produced by AuNPs@N-HCNs increased significantly under light irradiation. Comparing the size of AuNPs in carbon shell, 15 nm AuNPs were better than 2 nm in both enzyme-like activities and in vivo therapeutic effect. In vitro and in vivo studies demonstrated that under the synergistic effect of light-enhancing nanozyme catalysis and photothermal therapy, AuNPs@N-HCNs could induce cancer cell apoptosis and destroy tumors effectively, which provided evidence for the feasibility of tumor catalytic-photothermal treatment.

Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference.

BACKGROUND: Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment. RESULTS: Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells. CONCLUSIONS: This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Staphylococcus aureus-targeting peptide/surfactant assemblies for antibacterial therapy.

To address the challenge from microbial resistance, this work developed a surfactant with 18-carbon single hydrocarbon chain and multi-amine head groups (C18N3). After assembling with Staphylococcus aureus-targeting peptide (CARG), the obtained C18N3/CARG assemblies exhibited excellent antimicrobial activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in vitro and in vivo, in which the targeting peptide CARG bonded specifically to Staphylococcus aureus and C18N3 killed bacteria with a mechanism of membrane disruption. Importantly, C18N3 could also work as a ß-lactamase inhibitor to overcome the bacterial resistance to ß-lactam antibiotics through noncompetitive inhibition. The combination of ß-lactam antibiotic and C18N3/CARG assemblies more effectively suppressed methicillin-resistant Staphylococcus aureus in vitro and in vivo relative to equivalent dose of free antibiotic or C18N3. Thus, the antibacterial platform of antibiotic-carrying surfactant assemblies bearing bacteria-targeted peptides, in which C18N3 performed dual function, antibacterial agent and ß-lactamase inhibitor, may help fight against the difficult-to-treat infections.

Optimizing Parameters with FEM Model for 20CrMnTi Laser Shocking.

As a new surface treatment technology, laser shock peening (LSP) is a multi-point overlay process of single-point laser shock. In this study, the finite element method (FEM) was used to build a model of single-point laser shock, and the model was verified by experiments. The difference in residual stresses between the experimental and simulated results was less than 20%. Then, the effects of the stress field and deformation of 20CrMnTi with different laser shock parameters were simulated and analyzed. According to the mechanical response of 20CrMnTi to different laser shock parameters, the optimal shocking process parameters for single-point shocking via LSP were determined to be a shock energy of 5 J, a laser pulse width of 20 ns, and an impact number of 5. Lastly, a simulation of multi-point laser shock was performed with the optimal parameters, and the residual compressive stress values of multi-point impacts are close to those of single-point impacts under the same process conditions.