Cyclic Stress Research Articles

Green-Light-Triggered and Self-Calibrated Cascade Release of Nitric Oxide and Carbon Monoxide for Synergistic Glaucoma Therapy.

Glaucoma is an optic degenerative neuropathy that is driven by a vicious cycle of oxidative stress and mechanical stress. Current clinical treatments aim exclusively at alleviating mechanical stress by reducing the intraocular pressure (IOP). With the unattended oxidative stress, recurrence and deterioration of mechanical stress are inevitable. Nitric oxide (NO) and carbon monoxide (CO) are endogenous gaseous signaling molecules for vasodilation and anti-inflammation, respectively. Mounting evidence suggests an intricate interplay between NO and CO to mediate their biological roles, like how it takes two to dance a waltz. This leads to the concept of "gas waltz therapy" for glaucoma, in which NO is released to reduce IOP and stoichiometric CO is coreleased to suppress oxidative stress. CND570 is the first phototriggered cascade NO/CO donor, to the best of our knowledge. Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. CND570 exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both in vitro and in vivo models. Notably, CND570 treatment significantly reduces the oxidative stress associated with glaucoma. NO/CO-based gas waltz therapy is a promising new avenue for glaucoma treatment.

Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer.

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer.

Ultrasonic fatigue of superelastic Nitinol and in situ synchrotron observation of strain and damage

Superelastic Nitinol was tested at ultrasonic frequency in the high and very high cycle fatigue regime. Thin sheet specimens were initially preloaded to mimic crimping and deployment of Nitinol implants, which lead to a sample in a multi-phase state with martensitic phase in the middle and adjacent zones with austenitic phase. In situ synchrotron X-ray diffraction (XRD) was used to monitor cyclic strains over an entire ultrasonic cycle, and to compare the results with low frequency loading. Both austenitic and martensitic regimes showed similar sinusoidal elastic deformation at cycling frequencies 0.1 Hz and 18.3 kHz, and strains were comparable over the entire gauge section of the specimen. XRD data showed progressive growth of austenitic bands in formerly martensitic areas with increasing numbers of ultrasonic cycles. This increased specimen stiffness and cyclic stresses promoting crack initiation, which nearly exclusively occurred at cracked surface inclusions. The strain versus fatigue lifetime diagram shows a pronounced change in slope below 106 cycles. The overlapping properties measured at low and ultrasonic frequency demonstrate that ultrasonic fatigue testing is in principle appropriate for rapid characterization of the cyclic properties of Nitinol.

Human Breast Milk Exosomes: Affecting Factors, Their Possible Health Outcomes, and Future Directions in Dietetics

Background: Human breast milk is a complex biological fluid containing multifaceted biological compounds that boost immune and metabolic system development that support the short- and long-term health of newborns. Recent literature suggests that human breast milk is a substantial source of nutrients, bioactive molecules, and exosomes. Objectives: This review examines the factors influencing exosomes noted in human milk and the impacts of exosomes on infant health. Furthermore, it discusses potential future prospects for exosome research in dietetics. Methods: Through a narrative review of the existing literature, we focused on exosomes in breast milk, exosome components and their potential impact on exosome health. Results: Exosomes are single-membrane extracellular vesicles of endosomal origin, with an approximate radius of 20–200 nm. They are natural messengers that cells secrete to transport a wide range of diverse cargoes, including deoxyribonucleic acid, ribonucleic acid, proteins, and lipids between various cells. Some studies have reported that the components noted in exosomes in human breast milk could be transferred to the infant and cause epigenetic changes. Thus, it can affect gene expression and cellular event regulation in several tissues. Conclusions: In this manner, exosomes are associated with several pathways, including the immune system, oxidative stress, and cell cycle, and they can affect the short- and long-term health of infants. However, there is still much to learn about the functions, effectiveness, and certain impacts on the health of human breast milk exosomes.

Fatigue Analysis of Polylactide Manufactured by Fused Deposition Method of 3D Printing

Nowadays, 3D printing technology has gained popularity in various industrial sectors, especially in the field of developing new products. This technology allows for the layer-by-layer construction of 3D prototypes. This research primarily focuses on the fatigue performance of 3D-printed components made of Polylactide (PLA). PLA is a versatile material and has a diverse range of applications in packaging, medical, household items, etc. The specimens were made following the ASTM D638 standard using the Fused Deposition Modeling (FDM) technique. A fatigue test was carried out to investigate fatigue performance by fluctuating the loads and speed of the rotating beam fatigue tester. The finding reveals that materials break under variable strains at a stress magnitude is less than the material's ultimate tensile strength. Furthermore, it was discovered that the degree of the stress triggering fatigue failure reduces as the number of stress cycles increases. Fatigue failure is characterized as a time-delayed fracture due to cyclic stress. The finding reveals that PLA has a low fatigue strength of 19.62N.

Ochratoxin A and Its Role in Cancer Development: A Comprehensive Review.

Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research.

The spatial impact of a Western diet in enriching Galectin-1-regulated Rho, ECM, and SASP signaling in a novel MASH-HCC mouse model

BackgroundHepatocellular carcinoma (HCC) arising from metabolic dysfunction-associated steatohepatitis (MASH) presents a significant clinical challenge, particularly given the prevalence of the Western diet (WD). The influence of diet on the tumor microenvironment remains poorly understood. Galectin-1 (Gal-1) is a biomarker for HCC and has a crucial role in liver carcinogenesis. Our previous studies demonstrated that silencing Gal-1 effectively treats mouse HCC. However, the impacts of a WD on Gal-1 signaling on MASH to HCC progression are unknown, and this study addresses these knowledge gaps.MethodsWe developed a novel MASH-HCC mouse model. Using spatial transcriptomics and multiplex immunohistochemistry (IHC), we studied the effects of a WD on the liver and tumor microenvironment. By modulating Gal-1 expression through silencing and overexpression, we explored the location-specific impacts of WD on Gal-1 signaling.ResultsPathways such as Rho signaling, extracellular matrix (ECM) remodeling, and senescence-associated secretory phenotypes (SASP) were prominently activated in WD-induced metabolic dysfunction-associated fatty liver disease (MAFLD) and MASH-HCC, compared to healthy livers controls. Furthermore, Rho GTPase effectors, ECM remodeling, neutrophil degranulation, cellular stress, and cell cycle pathways were consistently enriched in human and mouse MASH-HCC. Spatially, these pathways were enriched in the tumor and tumor margins of mouse MASH-HCC. Additionally, there was a notable increase in CD11c and PD-L1-positive cells from non-tumor tissues to the tumor margin and inside the tumor of MASH-HCC, suggesting compromised immune surveillance due to WD intake. Moreover, MASH-HCC exhibited significant Gal-1 induction in N-Cadherin-positive cells, indicating enhanced epithelial-to-mesenchymal transition (EMT). Modulating Gal-1 expression in MASH-HCC further established its specific roles in regulating Rho signaling and SASP in the tumor margin and non-tumor tissues in MASH-HCC.ConclusionWD intake significantly influences vital cellular processes involved in Gal-1-mediated signaling, including Rho signaling and ECM remodeling, in the tumor microenvironment, thereby contributing to the development of MASH-HCC.

Undrained cyclic responses of sandy soils improved by soybean-induced calcium carbonate precipitation

ABSTRACT This study investigates the behaviour of sandy soils under cyclic conditions, emphasising the efficacy of soybean-induced calcium carbonate precipitation (SICP) treatment in mitigating liquefaction. Analysis of shear wave velocity and undrained cyclic responses was conducted, with a focus on understanding deformation response and development of excess pore pressure. Results revealed CaCO3 content as a definitive indicator for improvements in soil stiffness, with its distribution influenced by soil’s relative density and number of SICP injections. Enhanced cementation efficacy was observed in denser or deeper layers of sand column, attributed to prolonged SICP retention. A marked correlation between shear wave velocity and CaCO3 content highlighted SICP’s role in enhancing the liquefaction resistance of loose sandy soils. Dynamic triaxial testing showed the nuanced strain behaviours across varying relative densities and cyclic stress ratio (CSR) values, emphasising the strengthening influence of CaCO3 formations in the soil matrix. The empirical equation served as a testament to the potential of SICP in soil stabilisation endeavours. The intervention of SICP treatment presents a potent tool for bolstering soil stability, especially in regions susceptible to seismic activities. The insights garnered advocate for further research aimed at harnessing and optimising this soil improvement technique on a global scale.

Impact of neutron radiation induced defects on the surge current robustness of silicon carbide P‐intrinsic‐N diodes

AbstractSurge current (SC) capability is one of the main aspects of reliability for silicon carbide (SiC) power devices. In this work, the influences of neutron radiation‐induced defects on the SC capability and reliability of SiC P‐intrinsic‐N (PiN) diodes were comprehensively investigated. It was found that the surge capability of the diodes can be deteriorated even under the slightly enhanced formation of carbon‐vacancy‐related Z1/2 and EH6/7 defects introduced by neutron irradiation. Surprisingly, it was found that the forward voltage (VF) decreases with the increased SC and the stress cycles in the irradiated diodes, which is usually found to increase under the SC tests and attributed to the bipolar degradation (BPD). By using technology computer‐aided design simulation and deep‐level transient spectroscopy characterization, it was found that the significant self‐heating during surge stress leads to the annealing effect on the Z1/2 defects through the promoted recombination with the nearest and second neighbor carbon interstitials injected by irradiation, which thus plays a dominant role in the decrease of VF over the BPD.

Enhanced thermomechanical fatigue resistance in W10Re alloys: Microstructural and surface engineering approaches

Thermomechanical fatigue of refractory metals is commonly observed in high-temperature environments like first walls and divertors for proposed fusion reactors or X-ray anodes for medical imaging. Typically, alloying with rhenium or optimized microstructures are employed to counteract or delay the detrimental effects of fatigue in tungsten. Additionally, a novel concept is the utilization of surface structures to compensate cyclic thermal stresses. This work aimed to investigate the combination of these approaches, by comparing two W10Re alloys with vastly different microstructures, as well as engineered surface conditions of varying scales. Samples were subjected to thermocyclic fatigue under pulsed electron beam exposure, mimicking the surface temperatures typically encountered in a rotating X-ray anode. Analysis of several in-situ data streams, post-mortem investigations by metallography, and finite element methods revealed the interplay between microstructure and surface modifications. The columnar microstructure exhibited higher resistance to severe surface damage compared to the globular one, linked to the deflection of cracks along grain boundaries and subsequent melting. Coarse structuring was found to partly relieve the surface stresses during thermal cycling, preventing most of the damage accumulation. A full damage relief and performance equivalence between columnar and globular microstructure was achieved by engineering fine-structured surfaces, which led to a ten-fold increase in fatigue resistance over the non-structured condition.

Study on Dynamic Strength Characteristics of Sand Solidified by Enzyme-Induced Calcium Carbonate Precipitation (EICP).

Saturated sand foundations are susceptible to liquefaction under dynamic loads. This can result in roadbed subsidence, flotation of underground structures, and other engineering failures. Compared with the traditional foundation reinforcement technology, enzyme-induced calcium carbonate precipitation technology (EICP) is a green environmental protection reinforcement technology. The EICP technology can use enzymes to induce calcium carbonate to cement soil particles and fill soil pores, thus effectively improving soil strength and inhibiting sand liquefaction damage. The study takes EICP-solidified standard sand as the research object and, through the dynamic triaxial test, analyzes the influence of different confining pressure (σ3) cementation times (CT), cyclic stress ratio (CSR), dry density (ρd), and vibration frequency (f) on dynamic strength characteristics. Then, a modified dynamic strength model of EICP-solidified standard sand was established. The results show that, under the same confining pressure, the required vibration number for failure decreases with the increase in dynamic strength, and the dynamic strength increases with the rise in dry density. At the same number of cyclic vibrations, the greater the confining pressure and cementation times, the greater the dynamic strength. When the cementation times are constant, the dynamic strength of EICP-solidified sand decreases with the increase in the vibration number. When cementation times are 6, the dynamic strength of the specimens with CSR of 0.35 is 25.9% and 32.4% higher than those with CSR of 0.25 and 0.30, respectively. The predicted results show that the model can predict the measured values well, which fully verifies the applicability of the model. The research results can provide a reference for liquefaction prevention in sand foundations.

Nonlinear characteristics in the cylindrical roller bearing with raceway defects

Cylindrical roller bearings (CRBs) are subjected to significant cyclic stress under extreme operating conditions. This leads to the formation of localized wave defects on the raceway surface, such as burn. Thus, a new mathematical model is proposed to consider the local wave defects on the raceway caused by burns in this paper. Further, a dynamic model of CRB incorporating raceway defects is developed based on the contact relationships between components, and the proposed model is verified by measured acceleration responses. The effects of local wave defects on the nonlinear vibration characteristics of the bearings are studied and the results show that an increase in the number of defect waves reduces the additional displacement of rollers passing through the defect area, obscuring signal characteristics induced by the defect. Moreover, the presence of the defect influences the nonlinear interaction between the roller and raceway, which subsequently affects the cage whirling motion. This study of bearing dynamic behavior in this paper can contribute to the condition monitoring of bearings.

ToxProfiler: A novel human-based reporter assay for in vitro chemical safety assessment

In vitro chemical safety assessment often relies on simple and general cytotoxicity endpoint measurements and fails to adequately predict human toxicity. To improve the in vitro chemical safety assessment, it is important to understand the underlying mechanisms of toxicity. Here we introduce ToxProfiler, a novel human-based reporter assay that quantifies the chemical-induced stress responses at a single-cell level and reveals the toxicological mode-of-action (MoA) of novel drugs and chemicals. The assay accurately measures the activation of seven major cellular stress response pathways (oxidative stress, cell cycle stress, endoplasmic reticulum stress, ion stress, protein stress, autophagy and inflammation) that play a role in the adaptive responses prior to cellular toxicity. To assess the applicability of the assay in predicting the toxicity MoA of chemicals, we tested a set of 100 chemicals with well-known in vitro and in vivo toxicological profiles. Concentration response modeling and point-of-departure estimation for each reporter protein allowed for chemical potency ranking and revealed the primary toxicological MoA of chemicals. Furthermore, the assay could effectively group chemicals based on their shared toxicity signatures and link them to specific toxicological targets, e.g. mitochondrial toxicity and genotoxicity, and different human pathologies, including liver toxicity and cardiotoxicity. Overall, ToxProfiler is a quantitative in vitro reporter assay that can accurately provide insight into the toxicological MoA of compounds, thereby assisting in the future mechanism-based safety assessment of chemicals.

A novel approach to predicting liquefaction-induced settlements using Kolmogorov–Arnold Networks (KANs)

Soil liquefaction refers to the loss of strength and bearing capacity of soil under dynamic loads. Structures built on liquefied soils experience settlement. In this study, the newly developed Kolmogorov–Arnold Networks (KAN) method, an innovative artificial neural network technique, was utilized to predict liquefaction-induced settlement. The KAN method, which extends beyond the traditional Multi-Layer Perceptron (MLP) approach, was compared with the Random Forest method for benchmarking purposes. Using data derived from laboratory and field studies, models were constructed using both methods, and their performances were analyzed. According to the results, the KAN model outperformed the RF model in terms of R2, MAE, MSE, and RMSE metrics. Additionally, the feature importance analysis on the KAN model identified cyclic stress ratio (csr) and corrected SPT blow count (n1_60) as the most significant variables. These results underscore the potential of the KAN method in enhancing predictive accuracy and reliability in geotechnical applications, paving the way for its broader acceptance and implementation in real-world scenarios.

Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses.

Urinary collecting tubules form during kidney embryogenesis through the branching of the ureteric bud epithelium. A travelling mesenchyme niche of nephron progenitor cells caps each branching ureteric bud tip. These 'tip domain' niches pack more closely over developmental time and their number relates to nephron endowment at birth. Yet, how the crowded tissue environment impacts niche number and cell decision-making remains unclear. Here, through experiments and mathematical modelling, we show that niche packing conforms to physical limitations imposed by kidney curvature. We relate packing geometries to rigidity theory to predict a stiffening transition starting at embryonic day 15 in the mouse, validated by micromechanical analysis. Using a method to estimate tip domain 'ages' relative to their most recent branch events, we find that new niches overcome mechanical resistance as they branch and displace neighbours. This creates rhythmic mechanical stress in the niche. These findings expand our understanding of kidney development and inform engineering strategies for synthetic regenerative tissues.

Anti-Cancer Potential of Linear β-(1→6)-D-Glucan from Agaricus bisporus on Estrogen Receptor-Positive (ER+) Breast Cancer Cells

Mushroom β-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some β-D-glucans may exhibit direct antitumoral effects. It was previously observed that a β-(1→6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10–1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the β-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.

Cell structure development during cyclic deformation of near-[001] and near-[011] copper single crystals

Dislocation cell structures significantly influence the fatigue failure process. Research on the cell structures in multiple-slip-oriented copper single crystals has focused primarily on the [1‾11] orientation, whereas formation mechanisms and development processes of cell structures in [001] and [011] copper single crystals remain unclear. Therefore, this study examines the dislocation structures of near-[001] and near-[011] copper single crystals under cyclic deformation at high strain amplitudes. The cyclic stress–strain curve of the [011] crystals showed a distinct plateau at plastic shear strain amplitudes ≤7.5 × 10−3. In the plateau region, the dislocation structures consisted of cell structures along the (111) primary slip plane and matrix wall structures. Furthermore, (111) cell structures were formed in the single-slip deformation bands (DBs). After the plateau region, several types of new DBs could be observed due to the activation of multiple-slip systems. Multiple-slip DBs have a higher degree of plastic strain concentration than single-slip DBs, leading to the preferential formation of cell structures. For the near-[001] crystals, (111) cell structures were uniformly formed throughout the matrix, without the formation of DBs. The formation mechanism of the (111) cell boundary was independent of the stress axis and resulted from the interaction between the primary and coplanar slip systems.

In ovo betaine and heat acclimation affect hatching results, growth performance and immunity of the broilers under cyclicheatstress.

This study investigated the effects of in ovo betaine and thermal manipulation during incubation on growth performance, and some immune parameters of broilers under cyclic heat stress (CHS). Eggs were divided into 5 groups and incubated at 1) 37.8°C and 60% relative humidity (Control incubation and not-injected, CI); 2) eggs were incubated at CI and in ovo betaine injected into yolk sac on d 11 (E11) (CI + In ovo); 3) eggs were exposed to 38.8°C for 8h between 10 and 18d of incubation (heat acclimation, HA); 4) eggs were incubated at HA and in ovo betaine applied (HA + In ovo); 5) positive control: eggs were incubated at CI and injected with saline. Hatched chicks were raised under standard management conditions until 21 d, between 21 and 42 d half of the chickens in each incubation treatment were kept either at optimum (OPT) or at CHS. In ovo and HA did not affect hatching performance. In ovo increased thymus and spleen weights of chicks. Serum IgG was higher in HA + In ovo chicks. From d 7 to 21, in ovo chicks were heavier body weights, consumed more feed, and better feed conversion than those from CI. The body weights of HA chickens were similar in OPT and CHS on d 28 and 35. CHS reduced the body weight of CI chickens which was compatible with their feed consumption. Moreover, feed intake of HA + In ovo chickens exposed to CHS was higher than those not injected indicating that HA + In ovo enhanced thermoregulation of chickens under CHS.

Longitudinal tooth fracture indicating a questionable prognosis for an endodontist

Introduction and Objectives: Longitudinal fracture or vertical fracture of a tooth occurs at any level in the root and extends vertically. It has a high incidence of occurrence in the first molars. The most frequent sites to occur are the buccolingual surface and proximal surfaces of teeth. The etiology of fracture involves different factors in endodontically treated and non-endodontically treated teeth. Longitudinal fractures become the most challenging to diagnose and treat. This paper reviews these aspects of challenges and discusses the advantages and limitations of dental materials used for the treatment. Review Methods: PubMed and Google Scholar databases were searched for articles on longitudinal tooth fractures between 2007 and 2022. The 16 current articles were selected. Brief Description of the State of Knowledge: As per the review of the literature, longitudinal fracture of the tooth is the most common fracture to occur due to excessive forces on the root canal-treated tooth. This occurs in endodontically treated teeth due to long-term application of calcium hydroxide, cracks caused during root canal preparation extended by the pressure of root canal obturation, and in non-endodontically treated teeth due to cyclic and heavy masticatory stress, and habitual chewing of hard food especially in males. Summary: Functional and esthetic outcomes following longitudinal fracture treatment are important considerations in the case of anterior teeth. Longitudinal fracture or vertical fracture of a tooth occurs mostly in the first molars. It is crucial to identify and manage actors for good prognosis, as restoration at a time can reduce fracture extension prevent microleakage.

Manipulating Silver Nanoparticles with Biomolecular Corona Secreted from Vertebrates to Improve the Loading Capacity and Biocompatibility.

Silver nanoparticles (AgNPs) are widely used as nanoagents in biomedical fields, while it is still challenging to improve their loading capacity and biocompatibility in microcarrier delivering systems. Herein, the physicochemical properties of AgNPs were manipulated by forming biomolecular corona derived from bovine serum albumin (AC), and three organisms at various trophic levels: Chlorella sp. (BC1), Daphnia magna (BC2), and zebrafish (BC3). Proteins were identified by chemical composition analysis as the dominant components adsorbed on the surface of AgNPs. Proteomics indicated that AgNPs preferred to bind with low molecular weight (<50 kDa) and hydrophobic proteins with more positively charged residues. Consequently, AC and BC3 displayed stronger adsorption affinity on the surface of AgNPs than BC1 and BC2. Modifications by AC and BC3 effectively alleviated the oxidative stress and cell cycle arrest of AgNPs due to their superior antioxidative ability. However, BC3 with lower hydrophobicity enabled AgNPs to be more biocompatible than AC at subcellular level. Moreover, AC could significantly improve the loading capacity of AgNPs by Chlorella through enhancing caveolin-mediated endocytosis. Notably, owing to the adsorption of abundant Ca2+-binding proteins, BC3-AgNPs could also be internalized by microalgae via Ca2+-dependent clathrin-mediated endocytosis, which makes it a promising approach to deliver AgNPs. The results of this study would provide insights into the development of an efficient strategy to deliver AgNPs based on the microalgae carrier without altering its original properties and functionality.