High Resistance Research Articles

Physical, biochemical, and biological characterization of olive-derived lipid nanovesicles for drug delivery applications

AbstractExtracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

High level non-carbapenemase carbapenem resistance by overlaying mutations of mexR , oprD, and ftsI in Pseudomonas aeruginosa

ABSTRACT Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the mechanism of non-carbapenemase carbapenem resistance is still unclear. In the current study, we investigated the contributions of point mutations in mexR , oprD , and ftsI to carbapenem resistance in P. aeruginosa during in vivo evolution studies with consecutive clinical isolates. Real-time qPCR and Electrophoretic Mobility Shift Assay demonstrated that MexR (Gln55Pro) mutation increased MexAB efflux pump genes expression by altering MexR’s binding capacity, leading to a four- to eight-fold increase in meropenem MIC in the Pae d1 Green ∆ mexR and PAO1∆ mexR mutants. The OprD (Trp415*) truncation affected porin structure, and the constructed mutant Pae d1 Green oprD Trp415* increased meropenem MIC by 16-fold (from 0.25 to 4 µg/mL). The contribution of ftsI mutation to meropenem resistance was confirmed by clinical linkage analysis and was estimated to cause a two-fold increase in meropenem MIC by comparing the resistant clinical isolate with the Pae d1 Green oprD Trp415*∆ mexR double mutant. The study found that the oprD Trp415* allele alone accounts for the imipenem MIC in clinical isolates, while the ∆ mexR and ftsI Arg504Cys alleles do not contribute to imipenem resistance. In conclusion, we identified and explored the contributions of mexR , oprD, and ftsI mutations to high level non-carbapenemase carbapenem resistance in P. aeruginosa . These findings highlight the interplay of different mutations in causing non-carbapenemase carbapenem-resistance in P. aeruginosa . IMPORTANCE The emergence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant global health threat, complicating treatment options for infections caused by this pathogen. Understanding the mechanisms behind non-carbapenemase carbapenem resistance is critical for developing effective therapeutic strategies. This study provides crucial insights into how specific point mutations in key genes- mexR , oprD , and ftsI -contribute to carbapenem resistance, particularly the MexR (Gln55Pro) mutation’s effect on efflux pump expression and the OprD (Trp415*) truncation’s impact on porin structure. The findings elucidate the complex interplay of these mutations, highlighting their roles in conferring high-level resistance, and underscore the imperative for continued research to inform therapeutic strategies against CRPA infections.

Mitigation of Stress Corrosion Cracking in Additively Manufactured Stainless Steel by Laser Shock Peening

Abstract Use of laser powder bed fusion (LPBF) stainless steel in corrosive environments is attractive due to material's high corrosion resistance and fine feature resolution, which is advantageous for fluidic applications. For this implementation to be optimized, LPBF stainless steel parts must have reduced susceptibility to stress corrosion cracking (SCC), a failure mode that is of high risk for stainless steels. Laser shock peening (LSP) surface processing has been used to improve SCC resistance in wrought metals and has also been used to improve other material properties of additively manufactured metals. However, LSP has yet to be investigated for the improvement of SCC behavior in LPBF stainless steel. This article demonstrates that not only does LSP improve time to crack initiation of LPBF 316L stainless steel in SCC testing but also improves SCC behavior differently when applied to different surfaces of the build. To explain these results, residual stress, texture, dislocation distribution, hardness, microstructure, and fracture surfaces are investigated, linking different hydrogen embrittlement mechanisms to each of the two build orientations as well as the peened and un-peened conditions. These results are supported by matching the observed crack morphologies to those simulated with dynamic crack modeling, thereby demonstrating the impact of residual stress and plastic versus brittle failure upon the observed outcome.

New eco-friendly succinimide linseed oil resin: synthesis, characterization, DFT and docking studies for surface coating

Purpose The purpose of this study is to develop a new protective coating formulation for industrial use, using new eco-friendly succinimide linseed oil resin. Design/methodology/approach Epoxidized linseed oil and N-(4-hydroxy phenyl) succinimide are reacted to create succinimide-modified epoxy (SIE) compounds. The synthesized compound was confirmed by different analyses, gas chromatography, Fourier transform infrared, proton nuclear magnetic resonance and scanning electron microscopy. The prepared compound has been blended with a primer paint formulation, then their physical and mechanical properties have been studied. Density function theory is used to calculate Frontier molecular orbital including highest occupied molecular orbital and least unoccupied molecular orbital to indicate the charge transfer from molecule to biological media and molecular electrostatic potential map was used to indicate the chemically reactive zone suitable for drug action. Findings The results of the paint formulation confirmed their best performance and provided good mechanical properties and high chemical and corrosion resistance. Research limitations/implications Resin compounds are the most used antimicrobial additives. Other functionalities of these compounds, such as corrosion inhibitors, might be studied to see if they are suited for these applications. Practical implications Because of the efficiency of the SIE when incorporated with primer, paint against microbial has also been examined in silico using the docking study which contributed to the analysis of their protein binding. This type of epoxy compound is environmentally friendly and can be used as a biocide with different paint formulations. As a result, paint compositions including this compound as additives can be used as dual-purpose paint and for a variety of industrial applications. Originality/value This research demonstrates how a low-cost paint composition based on synthesized SIE compounds may be used as a dual-function paint for industrial use.

Anticorrosive coating from mussel-inspired hyperbranched epoxy resin with high mechanical properties and corrosion resistance

Anticorrosive coating from mussel-inspired hyperbranched epoxy resin with high mechanical properties and corrosion resistance

PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance.

Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-l-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC50 values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC50 was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC50, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.

The association of objective daytime sleepiness with impaired glucose metabolism in patients with obstructive sleep apnea: a multi-omics study.

To examine the joint effect of obstructive sleep apnea (OSA) and objective excessive daytime sleepiness (EDS) on glucose metabolism and the underlying mechanisms. We included 127 patients with OSA. The multiple sleep latency test (MSLT) and Epworth sleepiness scale (ESS) were used to assess objective and subjective EDS, respectively. Disordered glucose metabolism was defined as either a physician diagnosis or having fasting blood glucose levels ≥ 5.6 mmol/L. Values of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) higher than the median values of our sample were defined as high fasting insulin and insulin resistance. Serum metabolomics and fecal microbiota were used to explore underlying mechanisms. Lower MSLT values were associated with higher levels of fasting blood glucose, fasting insulin, and HOMA-IR. Furthermore, objective EDS was associated with increased odds of disordered glucose metabolism, elevated fasting insulin, and insulin resistance. Dysregulation of serum valine degradation and dysbiosis of fecal Bacteroides thetaiotaomicron were associated with impaired glucose metabolism in OSA with objective EDS. No association between subjective EDS and impaired glucose metabolism was observed. OSA with objective, but not subjective, EDS is associated with an increased risk of disordered glucose metabolism and insulin resistance. Dysregulation of valine degradation and dysbiosis of Bacteroides thetaiotaomicron appear to link objective EDS and disordered glucose metabolism in OSA.

Anatase‐reinforced PtZn@Silicalite‐1 structured catalysts boosting propane dehydrogenation

AbstractStructured catalysts exhibit the advantages of high diffusion efficiency and low heat transfer resistance, which have attracted increasing attention to non‐adiabatic gas–solid process. However, the metal‐supported coating catalysts face the problems of weaker bond strength and severe sintering, especially under the conditions of large flow rate and high temperature. Herein, metal@Silicalite‐1 structured catalysts with high adhesion and thermal stability were successfully prepared by hydroxylating the substrate with anatase. Rich surface Ti‐OH significantly strengthened the adhesion stability of the zeolite coating. In propane dehydrogenation reaction, the optimized PtZn@S‐1‐15Ti showed a high specific activity of 49.6 molC3H6·molPt−1·s−1 with propylene selectivity above 99% at 600°C. The introduction of anatase accelerated the aggregation of silicon sources and induced nucleation with growth content of zeolite increased by 3.6 times. It breaks the inherent contradiction between high loading amount and strong binding ability of coated catalysts, which broadens the avenues for industrial applications.

Identification of RppSLN from an Elite Landrace: A Major Locus Conferring Resistance to Southern Corn Rust in Maize (Zea mays L.)

Southern corn rust (SCR) is one of the most destructive foliar diseases in maize (Zea mays L.), resulting in significant yield losses. Therefore, the continuous identification of disease-resistant germplasm and the deployment of resistant hybrids is essential for durably controlling SCR. The objective of this research was to identify and characterize resistance loci against SCR in maize to expand disease management strategies. Here, we identified a maize landrace with high resistance to SCR ‘Silunuo’ (SLN) approaching complete immunity. We backcrossed it with a susceptible inbred line, N531, to generate a stable SCR-resistant introgression line N531_R. By crossing it with F35 (a susceptible inbred line), we created a large F2 segregating population and mapped a major SCR-resistant locus on chromosome 10, known as RppSLN. Based on the genome assembly and annotation, we found that RppSLN harbors two NBS-LRR (nucleotide binding site–leucine-rich repeat) genes, namely Zmays10G000430 and Zmays10G000440. These NBS-LRR genes were significantly induced during artificial inoculation with Puccinia polysora, suggesting that they might be candidate genes collectively contributing to the resistance level at this locus. In conclusion, this study identified a major SCR resistance locus directly isolated from a landrace, providing valuable support and information for expanding new disease-resistant germplasms and promoting the utilization of landraces.

Climate Response and Radial Growth Dynamics of Pedunculate Oak (Quercus robur L.) Plus Trees and Their Half-Sib Progeny in Periods of Severe Droughts in the Forest-Steppe Zone of Eastern Europe

The dendrochronological parameters of 97 pedunculate oak (Quercus robur L.) trees including 20 plus trees (142-year-old on average) and four half-sib families for four of them were analyzed considering also specifically years of the most severe droughts that were identified using average monthly air temperature and precipitation data. The tree-ring width (TRW) was mostly affected by air temperature that had the largest cross-dating indices (CDI), up to 78% maximum. However, the 32-year Brückner–Egeson–Lockyer cycle (a climatic cycle of approximately 30–40 years that correlates with sunspot activity) was more reflected in the TRW dynamics in plus trees than precipitation and air temperature. A high-frequency of abnormal TRW was clearly observed during drought periods and in the following 2–3 years. Tree radial-growth reduction due to drought stress varied significantly between families. The resistance to drought based on TRW was higher in the maternal plus oak trees than in progeny. Drought resulted in reduced growth during the subsequent year(s); hence, the minimum growth occurred after the actual climate event. Autumn–winter precipitation and weather conditions were of the greatest importance at the onset of active vegetation in April and May. The influence of air temperature on oak growth was the largest in March (r = 0.39, p < 0.05). The strongest positive correlation between precipitation and growth (with r up to 0.38) was observed in May 2023. Plus trees had a high adaptive potential due to the stability of radial growth during drought with high resistance (Rt = 1.29) and resilience (Rs = 1.09) indexes. The offspring of families 1 (Rt = 0.89, Rs = 0.89) and 2 (Rt = 1.04, Rs = 0.87) had similar resistance and resilience, but the recovery indices (Rc) for offspring in families 1, 2 and 3 exceeded the recovery values for plus trees. For offspring in families 3 and 4, the index values were lower. The revealed responses of wood growth of plus trees to climatic parameters estimated as resistance (Rt), resilience (Rs) and recovery (Rc) indexes and similar responses in their progeny can be used in breeding pedunculate oak for wood growth productivity and drought resistance.

Cross-linked structures reinforced the bamboo fiber/poly(lactic acid) composites with high heat resistance and their environmental impact through the life cycle assessment analysis

In order to prepare low-cost and heat-resistant poly(lactic acid) (PLA) composites, in this study, bamboo fiber (BF) was added to stereo-complex crystal PLA (SC-PLA) to prepare heat-resistant composites. Poly[(phenyl isocyanate)-co-formaldehyde] [a polyaryl polymethylene isocyanate (PAPI)] was used to form cross-linked structures between SC-PLA and BF, and the effects of PAPI-cross-linked structures on the crystallization properties, mechanical properties, and heat resistance of BF/SC-PLA composites with different BF contents were systematically investigated. When 15% BF was added, the mechanical properties of the composite were significantly improved. The tensile strength increased by 85.5% compared to the unmodified composite, reaching 34.7 MPa, which was even higher than that of the SC-PLA composite (33.1 MPa). In addition, in order to explore the impact of the PAPI-modified BF/SC-PLA composite on the environment and carbon emissions, a life cycle assessment (LCA) of the composites was conducted. The addition of BF effectively reduced the impact of the composite on the environment. Notably, the emissions of CO2 decreased by approximately 11.7%, and the freshwater, marine, and land ecotoxicity were also significantly reduced. This work provided a reference for the preparation of low-cost and heat-resistant PLA composites for heat-resistant food packaging and disposable tableware and expanded the application of PLA products in the field of heat-resistant materials.

High‐performance and flexible thermoelectric generator based on a robust carbon nanotube/BiSbTe foam

AbstractOrganic thermoelectric generators (TEGs) are flexible and lightweight, but they often have high electrical resistance, poor output power, and low mechanical durability, because of which their thermoelectric performance is poor. We used a facile and rapid solvent evaporation process to prepare a robust carbon nanotube/Bi0.45Sb1.55Te3 (CNT/BST) foam with a high thermoelectric figure of merit (zT). The BST sub‐micronparticles effectively create an electrically conductive network within the three‐dimensional porous CNT foam to greatly improve the electrical conductivity and the Seebeck coefficient and reinforce the mechanical strength of the composite against applied stresses. The CNT/BST foam had a zT value of 7.8 × 10−3 at 300 K, which was 5.7 times higher than that of pristine CNT foam. We used the CNT/BST foam to fabricate a flexible TEG with an internal resistance of 12.3 Ω and an output power of 15.7 µW at a temperature difference of 21.8 K. The flexible TEG showed excellent stability and durability even after 10,000 bending cycles. Finally, we demonstrate the shapeability of the CNT/BST foam by fabricating a concave TEG with conformal contact on the surface of a cylindrical glass tube, which suggests its practical applicability as a thermal sensor.

High-Performance Radiative Cooling Sunscreen.

Radiative cooling is a zero-energy-consumption cooling technology that shows great potential for outdoor human thermal management. To keep human skin comfortable in hot days, we herein develop a radiative cooling (RC) sunscreen that exhibits a low ultraviolet (UV) transmissivity (4.86%), a high solar reflectivity (90.19%), and a high mid-infrared emissivity (92.09%) to effectively provide both UV protection and skin cooling. As a result, the RC sunscreen exhibits a high cooling performance for decreasing the human skin temperature by 2.3-6.1 °C more than commercial sunscreens and 4.2-6.0 °C more than bare skin in a variety of outdoor scenarios in summer (e.g., low-humidity sunny days, high-humidity sunny days, and high-humidity cloudy days). In addition, the RC sunscreen also shows a good UV stability (12 h, 125 W), a high water resistance (106°), a long working life (30 days), and a good biocompatibility, thereby exhibiting promising commercial potentials in the sunscreen market.

Machine learning potential for the Cu-W system

Combining the excellent thermal and electrical properties of Cu with the high abrasion resistance and thermal stability of W, Cu-W nanoparticle-reinforced metal matrix composites and nano-multilayers are finding applications as brazing fillers and shielding material for plasma and radiation. Due to the large lattice mismatch between fcc Cu and bcc W, these systems have complex interfaces that are beyond the scales suitable for methods, thus motivating the development of chemically accurate interatomic potentials. Here, a neural network potential (NNP) for Cu-W is developed within the Behler-Parrinello framework using a curated training dataset that captures metallurgically relevant local atomic environments. The Cu-W NNP accurately predicts (i) the metallurgical properties (elasticity, stacking faults, dislocations, thermodynamic behavior) in elemental Cu and W, (ii) energies and structures of Cu-W intermetallics and solid solutions, and (iii) a range of fcc Cu/bcc W interfaces, and exhibits physically reasonable behavior for solid W/liquid Cu systems. As will be demonstrated in forthcoming work, this near accurate NNP can be applied to understand complex phenomena involving interface-driven processes and properties in Cu-W composites. Published by the American Physical Society 2024

Optical and electrical properties of proton-implanted p-GaSb for electrical isolation

Abstract The effect of proton implantation as solation implant and subsequent annealing on the optical absorption and electrical resistivity of low-bandgap p-GaSb is reported. The measured transmittance spectra indicates that implantation creates a distribution of energy levels extending into the bandgap. Electrical measurements show that the average sheet resistance of the implanted layer increases only by an order of magnitude from its pre-implantation value at a proton dose of ~1013 cm-2 followed by 200°C annealing. It is also shown that annealing reduces the implantation-induced optical absorption while still retaining a high electrical resistivity.

The Impact of Reinforcement Ratio on the Punching Shear of CFRP Grid-Reinforced Concrete Two-Way Slabs

Corrosion of steel reinforcement in concrete slabs undermines structural durability and shortens the lifespan of concrete structures. Carbon Fiber-Reinforced Polymer (CFRP) is a promising material offering benefits such as high strength, corrosion resistance, and light weight. This study aims to investigate the punching shear performance of concrete slabs reinforced with CFRP grids, focusing on the effects of different reinforcement ratios. A series of experiments were conducted on two-way concrete slabs reinforced solely with CFRP grids to assess their punching shear resistance. Experimental results show that the CFRP grid achieves an ultimate tensile strength of 2181 MPa, with the cracking load of CFRP grid-reinforced slabs reaching approximately 20% of the ultimate load, highlighting a strong correlation between the ultimate load and grid reinforcement ratio. The observed punching failure exhibited clear brittle characteristics, characterized by the formation of radial and circumferential cracks on the tensile surface of the slab. The reinforcement ratio significantly influences the failure mode of the slabs; as the reinforcement ratio increases, the ultimate punching loads also increase. Additionally, a mathematical formula is proposed to predict the punching bearing capacity, achieving calculation errors below 20%. These findings contribute valuable insights into using CFRP grids as primary reinforcement, enhancing the design and application of durable concrete slab structures.

Isolation and Identification of Bacterial Pathogens from Blood Cultures in a Tertiary Care Hospital and Their Clinical Correlation

Objective: This study aimed to isolate and identify bacterial pathogens from blood cultures of patients with suspected bloodstream infections (BSIs) in a tertiary care hospital, analyze their antimicrobial susceptibility patterns, and establish clinical correlations. Methods: A cross-sectional study was conducted in the Microbiology Department of a tertiary care hospital. Blood samples from 60 patients were collected aseptically, processed using BACTEC, and cultured on blood and MacConkey agar. Bacterial isolates were identified based on colonial morphology, Gram staining, and biochemical tests. Antibiotic susceptibility testing was performed using the modified Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The overall culture positivity rate was 26%, with higher positivity among female patients (31.57%) and neonates or infants under six months (26%). Klebsiella pneumoniae was the most frequently isolated pathogen (53.33%), followed by Staphylococcus aureus (20.00%), Escherichia coli (13.33%), and Citrobacter species (13.33%). Klebsiella pneumoniae showed high resistance to ceftazidime and piperacillin, while remaining sensitive to cefoperazone and tobramycin. Staphylococcus aureus isolates were resistant to penicillin and erythromycin but sensitive to vancomycin and cefazolin. The prevalence of multidrug resistance among isolates underscores the need for targeted empirical therapy. Conclusion: Klebsiella pneumoniae emerged as the primary pathogen in BSIs, with significant resistance to commonly prescribed antibiotics. These findings highlight the necessity for enhanced infection control measures, especially in NICUs, and the implementation of local antibiograms to guide effective antibiotic therapy and mitigate resistance trends. Further research across multiple centers is recommended to validate these findings and inform broader clinical guidelines.

Antibiotic Resistance in Mycobacterium Tuberculosis and Non-Tuberculous Mycobacteria

Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) antibiotic resistance presents an important challenge to the treatment of mycobacterial infections. The therapeutic approaches are complicated by the resistance of both MTB and NTM to a variety of antibiotics. Resistance to first-line drugs such as isoniazid, rifampicin, ethambutol, and streptomycin has been consistently increasing in MTB, underscoring the necessity of effective treatment strategies. Conversely, the necessity of species-specific treatment regimens is underscored by the high resistance rates of NTM species, such as Mycobacterium avium complex, M. kansasii, and M. abscessus complex, to commonly used anti-tuberculosis pharmaceuticals. A combination of intrinsic and acquired factors are involved in the mechanisms of antibiotic resistance in these mycobacteria. Features such as biofilm formation, thick cell walls, and reduced drug uptake are responsible for intrinsic resistance in NTM, whereas acquired resistance can develop as a result of protracted antibiotic exposure. Understanding these resistance mechanisms is essential for the development of new therapies and the prevention of the increasing prevalence of drug resistance in mycobacterial infections. The significance of continuous surveillance, species-specific treatment protocols, and the development of novel antimicrobial agents to effectively manage mycobacterial diseases is emphasized by the prevalence of antibiotic resistance in MTB and NTM. This review article focuses on the molecular mechanisms that have resulted in the development of resistance in both MTB and NTMs, as well as the extent to which various classes of antimycobacterial drugs act.

Production, Characterization, and Application of Hydrophobin-Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near-Infrared Imaging.

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual-functional fusion protein tLyP-1-MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor-penetrating peptide tLyP-1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP-1-MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin-based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer.

Machining Characteristics During Short Hole Drilling of Titanium Alloy Ti10V2Fe3Al

The single-phase titanium ß-alloy Ti10V2Fe3Al (Ti-1023) has been widely used in the aerospace industry due to its unique mechanical properties, which include high fatigue strength and fracture toughness, as well as high corrosion resistance. On the other hand, these unique properties significantly hinder the cutting processes of this material, especially those characterized by a closed machining process area, such as drilling. This paper is devoted to the study of the short hole drilling process of the above-mentioned titanium alloy using direct measurements and numerical modeling. Measurements of the cutting force components in the drilling process and determination of the resultant cutting force and total cutting power were performed. The macro- and microstructure of chips generated during drilling were analyzed, and the dependence of the chip compression ratio and the distance between neighboring segments of serrated chips on cutting speed and drill feed was determined. Experimental studies were supplemented by determining the temperature on the lateral clearance face of the drill’s outer cutting insert in dependence on the cutting modes. For the modeling of the drilling process using the finite element model, the parameters of the triad of component submodels of the numerical model were determined: the machined material model, the model of contact interaction between the tool and the machined material, and the fracture model of the machined material. The determination of these parameters was performed through the DOE sensitivity analysis. The target values for performing this analysis were the total cutting power and the distance between neighboring chip segments. The maximum deviation between the simulated and experimentally determined values of the resulting cutting force is no more than 25%. At the same time, the maximum deviation between the measured values of the temperature on the lateral clearance face of the drill’s outer cutting insert and the corresponding simulated values is 26.1%.