Convolutional Neural Network-Driven Impedance Flow Cytometry for Accurate Bacterial Differentiation.

Impedance flow cytometry (IFC) has been demonstrated to be an efficient tool for label-free bacterial investigation to obtain the electrical properties in real time. However, the accurate differentiation of different species of bacteria by IFC technology remains a challenge owing to the insignificant differences in data. Here, we developed a convolutional neural networks (ConvNet) deep learning approach to enhance the accuracy and efficiency of the IFC toward distinguishing various species of bacteria. First, more than 1 million sets of impedance data (comprising 42 characteristic features for each set) of various groups of bacteria were trained by the ConvNet model. To improve the efficiency for data analysis, the Spearman correlation coefficient and the mean decrease accuracy of the random forest algorithm were introduced to eliminate feature interaction and extract the opacity of impedance related to the bacterial wall and membrane structure as the predominant features in bacterial differentiation. Moreover, the 25 optimized features were selected with differentiation accuracies of >96% for three groups of bacteria (bacilli, cocci, and vibrio) and >95% for two species of bacilli (Escherichia coli and Salmonella enteritidis), compared to machine learning algorithms (complex tree, linear discriminant, and K-nearest neighbor algorithms) with a maximum accuracy of 76.4%. Furthermore, bacterial differentiation was achieved on spiked samples of different species with different mixing ratios. The proposed ConvNet deep learning-assisted data analysis method of IFC exhibits advantages in analyzing a huge number of data sets with capacity for extracting predominant features within multicomponent information and will bring about progress and advances in the fields of both biosensing and data analysis.

Harmonic Scalpel Versus Monopolar Electrotome in Endoscopic-Assisted Transaxillary Dual-Plane Augmentation Mammaplasty: A Retrospective Study in 122 Patients.

BACKGROUND: The transaxillary approach of breast augmentation is the most popular method in Asia, but longer period of recovery was observed in spite of the assistance of endoscope. OBJECTIVES: Introducing the ultrasonic dissection devices might be a solution to minimizing tisue damage thus relieving pain and shortening the period of recovery. METHOD: Between March 2020 and September 2022, we retrospectively reviewed the cases of 122 patients underwent endoscopic augmentation mammoplasty via the transaxillary approach using either the monopolar electrotome (ME) alone or assisted with Harmonic Scalpel (HS) in defining the retropectoral pocket and severing the pectoralis major muscle. RESULT: The total drainage volume was significantly lower in the HS group than ME group (74.33 ± 48.81 vs. 180.30 ± 125.10 mL; p < 0.0001). VAS score of the first 24 hour after surgery of the ME group was significantly higher than that of the HS group (6.10 ± 1.27 vs. 2.88 ± 1.29, p < 0.0001). Operation time in HS group was reduced compared to ME group (113.1 ± 14.46 mins vs. 131.3 ± 35.51 mins, p < 0.001). The duration of drainage placement (1.08 ± 0.27 vs. 2.72 ± 1.18 days) and hospital stay after surgery (3.08 ± 0.42 vs. 5.64 ± 2.78 days; p < 0.0001) were largely reduced in HS group. CONCLUSION: The assistance of Harmonic Scalpel significantly reduced total postoperative drainage, relieved pain and shortened operation time, length of drainage placement and hospital stay compared to using monopolar electrotome alone in endoscopic-assisted transaxillary dual-plane augmentation mammaplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma.

Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.

Synthesis of dual-phase Ti3O5/Ti4O7 nanofibers for efficient adsorption of SARS-CoV-2.

In this study, we synthesized the dual-phase Ti3O5/Ti4O7 nanofibers for efficient adsorption of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a life-threatening virus being taking millions of people lives. The Ti3O5/Ti4O7 nanofibers were synthesized by preparation of H2Ti3O7 precursor, polydopamine coating and furnace calcination. Protein and phospholipid adsorption assays showed that the dual-phase nanofibers had much higher affinity to both the model molecules bovine serum album (BSA) and phosphatidylethanolamine (PE) than the control single-phase Ti6O11 nanofibers. Consistently, the dual-phase nanofibers exhibited much stronger adsorption ability to SARS-CoV-2 pseudovirus than Ti6O11. This study sheds a light on titanium oxide nanomaterials to adsorb SARS-CoV-2 for avoiding its infection and for capturing it during rapid virus detection.

Modification of cellulose microfibers by polyglutamic acid and mesoporous silica nanoparticles for Enterovirus 71 adsorption.

In this study, we synthesized a novel kind of cellulose-based microfibers for efficient adsorption of Enterovirus 71 (EV71), the leading causative agent of life-threatening hand, foot and mouth disease. The initial cellulose microfibers (CEL) were activated by (3-aminopropyl) triethoxysilane (APTES), and then covalently modified by polyglutamic acid (PGA) and mesoporous silica nanoparticles (MSN), obtaining the microfibers CEL-PGA-MSN. Owing to the electrostatic interaction between the negatively charged components (i.e., PGA and MSN) and positively charged amino acids of the epitope of EV71 capsid protein VP2 (VP2-ep), the obtained microfibers strongly adsorbed the epitope, and exhibited high EV71-adsorption capacity. This study sheds a novel light on development of cellulose-based materials for application in virus-capturing equipment.

Facet Energy and Reactivity versus Cytotoxicity: The Surprising Behavior of CdS Nanorods.

Responsible development of nanotechnology calls for improved understanding of how nanomaterial surface energy and reactivity affect potential toxicity. Here, we challenge the paradigm that cytotoxicity increases with nanoparticle reactivity. Higher-surface-energy {001}-faceted CdS nanorods (CdS-H) were less toxic to Saccharomyces cerevisiae than lower-energy ({101}-faceted) nanorods (CdS-L) of similar morphology, aggregate size, and charge. CdS-H adsorbed to the yeast's cell wall to a greater extent than CdS-L, which decreased endocytosis and cytotoxicity. Higher uptake of CdS-L decreased cell viability and increased endoplasmatic reticulum stress despite lower release of toxic Cd(2+) ions. Higher toxicity of CdS-L was confirmed with five different unicellular microorganisms. Overall, higher-energy nanocrystals may exhibit greater propensity to adsorb to or react with biological protective barriers and/or background constituents, which passivates their reactivity and reduces their bioavailability and cytotoxicity.

Synthesis of mesoporous wall-structured TiO2 on reduced graphene oxide nanosheets with high rate performance for lithium-ion batteries.

Mesoporous wall-structured TiO2 on reduced graphene oxide (RGO) nanosheets were successfully fabricated through a simple hydrothermal process without any surfactants and annealed at 400 °C for 2 h under argon. The obtained mesoporous structured TiO2 -RGO composites had a high surface area (99 0307 m(2) g(-1)) and exhibited excellent electrochemical cycling (a reversible capacity of 260 mAh g(-1) at 1.2 C and 180 mAh g(-1) at 5 C after 400 cycles), demonstrating it to be a promising method for the development of high-performance Li-ion batteries.

Genotoxicity and Cytotoxicity of Cadmium Sulfide Nanomaterials to Mice: Comparison Between Nanorods and Nanodots.

Cadmium sulfide (CdS) nanomaterials (such as CdS nanodots or nanorods) are widely used in optical, electronic, and biological applications. Large-scale production and use of these materials will likely result in accidental and incidental releases, which raise concerns about their potential environmental and human-health impacts. Most studies on toxicity of Cd-containing nanomaterials have focused on nanodots, and the relative toxicity of Cd-containing nanorods is not well understood. Here, we compared genotoxicity and cytotoxicity of CdS nanorods (30-50 nm diameter, 500-1100 nm length) and cubic CdS nanodots (3-5 nm) in mice by examining total cadmium accumulation in organs, acute toxicity, DNA damage, spermatozoon viability and abnormality, kidney and liver damage, and oxidative stress. Compared with (smaller) nanodots, nanorods resulted in relatively low bioaccumulation, acute toxicity, and damage to spermatozoa and the tested organs. Differences in toxicity between CdS nanodots and nanorods could not be fully explained by differences in their metal ion (Cd2+) release patterns, based on control tests with mice gavaged with dissolved CdCl2 at equivalent concentrations. This underscores that toxicity of metallic nanomaterials could not be solely predicted based either on their elemental composition or on the amount of ions released before receptor intake. Particle morphology (including size) may also need to be considered.

Reg⠢γ promotes the proliferation, and inhibits inflammation response of macrophages by Akt, STAT3 and NF-κB pathways.

As an inflammatory regulator, intestinal regenerating islet-derived 3 gamma (RegⅢγ) contributes to alleviating liver injury in liver diseases and colitis. However, it is unclear whether hepatic RegⅢγ exerts a vital impact on liver regeneration (LR). In this study, the expression profile and localization of RegⅢγ in LR were demonstrated by microarray analysis, qRT-PCR and immunofluorescence staining. Then, RAW264.7 cells with RegⅢγ deficiency and overexpression were obtained by the CRISPR/Cas9 system and lentivirus infection, respectively. MTT, flow cytometry, EdU, transwell, neutral red phagocytosis, and NO assays were performed to detect the functions of RegⅢγ in RAW264.7 cell proliferation and inflammation. Finally, the regulatory mechanism of RegⅢγ was explored by co-immunoprecipitation and Western blot assays. According to our findings, RegⅢγ showed significant expression changes in Kupffer cells during LR, and RegⅢγ overexpression stimulated the viability, proliferation, phagocytosis and migration of RAW264.7 cells, whereas RegⅢγ deficiency reversed these effects. Similarly, RegⅢγ overexpression facilitated the expression of HO-1 and IL-10, while RegⅢγ deficiency promoted NO production and p-Akt, p-STAT3, p-p65 and TNF-α expression. In conclusion, RegⅢγ may facilitate LR by promoting the proliferation of macrophages and inhibiting their inflammatory response through Akt, STAT3 and NF-κB pathways in the priming stage of LR.

Association of metals and bisphenols exposure with lipid profiles and dyslipidemia in Chinese adults: Independent, combined and interactive effects.

BACKGROUND: Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism. METHODS: Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model. RESULTS: Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C. CONCLUSIONS: Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects.

Bisphenol mixtures, metal mixtures and type 2 diabetes mellitus: Insights from metabolite profiling.

BACKGROUND: Little is known about the combined effect of bisphenol mixtures and metal mixtures on type 2 diabetes mellitus (T2DM) risk, and the mediating roles of metabolites. METHODS: The study included 606 pairs of T2DM cases and controls matched by age and sex, and information of participants was collected through questionnaires and laboratory tests. Serum bisphenol and plasma metal concentrations were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Widely targeted metabolomics was employed to obtain the serum metabolomic profiles. Conditional logistic regression models were used to assess the single associations of bisphenols and metals with T2DM risk after multivariable adjustment. Additionally, the joint effects of bisphenol mixtures and metal mixtures were examined using quantile-based g-computation (QG-C) models. Furthermore, differential metabolites associated with T2DM were identified, and mediation analyses were performed to explore the role of metabolites in the associations of bisphenols and metals with T2DM risk. RESULTS: The results showed bisphenol mixtures were associated with an increased T2DM risk, with bisphenol A (BPA) identified as the primary contributor. While the association between metal mixtures and T2DM remained inconclusive, cobalt (Co), iron (Fe), and zinc (Zn) showed the highest weight indices for T2DM risk. A total of 154 differential metabolites were screened between the T2DM cases and controls. Mediation analyses indicated that 9 metabolites mediated the association between BPA and T2DM, while L-valine mediated the association between Zn and T2DM risk. CONCLUSIONS: The study indicated that BPA, Co, Fe, and Zn were the primary contributors to increased T2DM risk, and metabolites played a mediating role in the associations of BPA and Zn with the risk of T2DM. Our findings contribute to a better understanding of the mechanisms underlying the associations of bisphenols and metals with T2DM.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

The Application of Anatomy Combined With Ultrasound Knife in Transaxillary Endoscopic Biplane Breast Augmentation.

Objective: We aim to clarify the vascular and nerve anatomy of the breast and combine it with an ultrasound knife to use in transaxillary endoscopic biplane breast augmentation. Methods: This study is a retrospective review of patients undergoing transaxillary endoscopic biplane breast augmentation between October and October 2021. Related variables were collected using a standardized data collection template. The detailed process of the transaxillary endoscopic biplane breast augmentation under anatomy instruction is carefully described in this study, and the postoperative effect was closely observed. Results: Sixty-three female patients underwent transaxillary endoscopic biplane breast augmentation. The average implants volume counted 242.46 ± 31.34 cc, and the average operation time was 155.92 ± 22.34 min. Patients were followed up for a mean of 13.67 months (range, 3-27 months), and most of the patients achieved good postoperative results and no severe complications and were satisfied with both appearance and function. Conclusions: The application of anatomy combined with an ultrasound knife in transaxillary endoscopic biplane breast augmentation is a promising way to achieve good breast shapes with high patient satisfaction and is worthy of clinical promotion and application.

Deep Learning Assisted Microfluidic Impedance Flow Cytometry for Label-free Foodborne Bacteria Analysis and Classification.

According to the urgent need for rapid detection and identification of foodborne bacteria to prevent public health event, a microfluidic electrical impedance flow cytometry assisted with convolutional neural network (ConvNet) based deep learning algorithm was proposed in this study to analyze the impedance signals of bacteria. With the assistance of the deep learning algorithm, Escherichia coli (EPEC), Salmonella enteritidis (SE) and Vibrio parahaemolyticus (VP) were identified with an accuracy of 100%. The proposed impedance based analysis system can be potentially applied for pre-classification of different subtypes of bacteria in a label-free manner.Clinical Relevance-The whole platform can be miniaturized and applied for point-of-care testing (POCT) of pathogenic bacteria detection.

Tumor purity as a prognosis and immunotherapy relevant feature in cervical cancer.

BACKGROUND: Tumor purity plays a vital role in the biological process of solid tumors, but its function in gynecologic cancers remains unclear. This study explored the correlation between tumor purity and immune function of gynecological cancers and its reliability as a prognostic indicator of immunotherapy. METHODS: Gynecological cancer-related datasets were downloaded from The Cancer Genome Atlas (TCGA). Tumor purity was calculated by the ESTIMATE algorithm. A LASSO Cox regression analysis was performed to construct the risk score model. A Kaplan-Meier Plotter was used to explore the relationships between tumor purity and cancer prognosis. We performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) to explore the pathways in the subgroups. A nomogram was used to quantitatively assess the cancer prognosis. RESULTS: Tumor purity was negatively correlated with B cell infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Approximately 420 genes were positively associated with B cell infiltration and CESC prognosis and were enriched in immune-related signaling pathways. There were 11 key genes used to construct a risk score model. The low-risk group had a higher immune score and better prognosis than the high-risk group. A nomogram based on risk score, T stage, and clinical-stage had good predictive value in quantitatively evaluating CESC prognosis. CONCLUSIONS: This study is the first to reveal the correlation between tumor purity and immunity in CESC and suggests that low-risk patients may be more sensitive to immunotherapy. This provides a theoretical basis for the clinical treatment of CESC.

Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway.

Nonalcoholic steatohepatitis (NASH) is a global public health challenge. Overwhelmed oxidative stress and impaired autophagy play an important role in the progression of NASH. Chemerin is an adipokine that has attracted much attention in inflammation and metabolic diseases. This study aimed to examine the effects of chemerin in NASH and its association with oxidative stress and autophagy. In this study, chemerin was found to significantly ameliorate high-fat diet (HFD) induced NASH, marked by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), decreased insulin resistance (IR) and leptin resistance (LR), and improved liver lesions. Besides, chemerin prevented enhanced oxidative stress in NASH mice by regulating the antioxidant defense system (MDA downregulation and upregulation of superoxide dismutase (SOD)). Moreover, chemerin contributed to the alleviation of NASH through autophagy activation (p62 downregulation, and upregulation of beclin-1 and LC3). Furthermore, these effects were related to increased phosphorylation of JAK2-STAT3 stimulated by chemerin, which could be inhibited by the CMKLR1 specific inhibitor α-NETA. In conclusion, excess chemerin highly probably ameliorated NASH by alleviating oxidative stress and promoting autophagy, the mechanism responsible for this process was related, at least in part, to the increased phosphorylation of JAK2-STAT3 stimulated by chemerin/CMKLR1. Rh-chemerin may represent promising therapeutic targets in the treatment of NASH.

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer.

The members of the Nedd4-like E3 family participate in various biological processes. However, their role in clear cell renal cell carcinoma (ccRCC) is not clear. This study systematically analyzed the Nedd4-like E3 family members in ccRCC data sets from multiple publicly available databases. NEDD4L was identified as the only NEDD4 family member differentially expressed in ccRCC compared with normal samples. Bioinformatics tools were used to characterize the function of NEDD4L in ccRCC. It indicated that NEDD4L might regulate cellular energy metabolism by co-expression analysis, and subsequent gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A prognostic model developed by the LASSO Cox regression method showed a relatively good predictive value in training and testing data sets. The result revealed that NEDD4L was associated with biosynthesis and metabolism of ccRCC. Since NEDD4L is downregulated and dysregulation of metabolism is involved in tumor progression, NEDD4L might be a potential therapeutic target in ccRCC.

Antifungal effects of BiOBr nanosheets carrying surfactant cetyltrimethylammonium bromide.

BiOBr nanosheets are important photocatalytic nanomaterials. However, their biological effects remain to be explored. In this study, we investigated the antifungal effect of BiOBr nanosheets on Candida albicans. Strikingly, the nanosheets strongly inhibited the growth of C. albicans [IC50=(96±4.7) mg/L], hyphal development and biofilm formation. Compareed to the antifungal effect of the cationic surfactant cetyltrimethylammonium bromide, the inhibitory effect of the nanosheets on fungal pathogen was attributed to cetyltrimethylammonium bromide adsorbed by the nanosheets. Thermal gravity analysis and cetyltrimethylammonium bromide release experiment indicated that only 0.42% cetyltrimethylammonium bromide on BiOBr nanosheets was released. Taken together, this study uncovers the contribution of surfactant released from the nanosheets to their antifungal activity.

Lead sulfide nanoparticles increase cell wall chitin content and induce apoptosis in Saccharomyces cerevisiae.

Although there have been numerous studies on bacterial toxicity, the cytotoxicity of nanoparticles toward fungi remains poorly understood. We investigated the toxicity of various sizes of lead sulfide particles against the important model fungus, Saccharomyces cerevisiae. The smallest particle exerted the highest toxicity, inhibiting cell growth and decreasing cell viability, likely reflecting reduced sedimentation and persistent cell wall attack. In response to cell wall stress, S. cerevisiae showed an increase in the cell wall chitin content and the overexpression of FKS2 and PRM5, two genes of the cell wall integrity signaling pathway. Cell wall stress increased the concentration of intracellular reactive oxygen species, leading to mitochondrial dysfunction and cell apoptosis. The contribution of dissolved lead ions to the overall toxicity was negligible. These findings provide the first demonstration of the physiological protective response of a fungus toward nanoparticles, thereby contributing useful information to the assessment of the environmental impact of metal nanoparticles.

A novel toxicity mechanism of CdSe nanoparticles to Saccharomyces cerevisiae: enhancement of vacuolar membrane permeabilization (VMP).

Cadmium selenide (CdSe) nanoparticles are implemented in a wide range of applications, but their potential risk to the ecosystem, especially to the organisms essential for the maintenance of ecosystem homeostasis, such as fungal populations, plants and bacteria, remains to be elucidated. In this study, we investigated their toxicity to one of the most important fungal model organisms, Saccharomyces cerevisiae. Growth inhibition assays revealed that the synthesized CdSe nanoparticles with the sizes of 20-30 nm had strong inhibitory effect on yeast growth (IC50=80 ppm). This toxicity was not attributed to mitochondrial dysfunction and autophagy, but was dependent on End3-mediated endocytosis, and was associated with reactive oxygen species (ROS) accumulation and an enhancement of vacuolar membrane permeabilization (VMP). These results reveal a key role of the vacuole during the interaction between CdSe nanoparticles and yeast cells.