Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Drinking brick tea containing high fluoride increases the prevalence of osteoarthritis in Tibetan, China.

The prevalence of osteoarthritis (OA) in Tibetans is higher than that in Han, while Tibetans have a habit of drinking brick tea with high fluoride. A cross-sectional study was conducted to explore the association between fluoride exposure in drinking brick tea and OA. All subjects were divided into four groups by the quartiles (Q) of tea fluoride (TF) and urine fluoride (UF). ROC was plotted and OR were obtained using logistic regression model. The prevalence of OA in the Q3 and Q4 group of TF were 2.2 and 2.7 times higher than in the Q1 group, and the prevalence of OA in the Q2, Q3 and Q4 group of UF were 3.2, 3.5, and 4.1 times higher than in the Q1 group. ROC analysis showed the cutoff values were 4.523 mg/day (TF) and 1.666 mg/L (UF). In conclusion, excessive fluoride in drinking brick tea could be a risk factor for developing OA.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China.

To investigate the potential association between BMP2 single nucleotide polymorphisms (SNPs) and brick-tea-type skeletal fluorosis risk in cross-sectional case-control study conducted in Sinkiang and Qinghai, China, a total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled. Using the standard WS/192-2008 (China), 221 skeletal fluorosis cases were diagnosed, including 123 Tibetans and 98 Kazakhs. Logistic regressions 2 analysis did not find the association between SNPs (Rs235764, Rs235739 and Rs996544) and skeletal fluorosis. Genetic models, linkage disequilibrium (LD) and haplotype analysis were not found to be associated with risk of skeletal fluorosis after adjustment by age and sex (P>0.05).Our data suggested that Rs 235764, Rs 235739 and Rs 996544 were not linked susceptibility for skeletal fluorosis in our cross-sectional case-control study.

Pinecone-Inspired Nanoarchitectured Smart Microcages Enable Nano/Microparticle Drug Delivery.

Drug delivery plays a vital role in medicine and health, but the on-demand delivery of large-sized drugs using stimuli-triggered carriers is extremely challenging. Most present capsules consist of polymeric dense shells with nanosized pores (<10 nm), thus typically lack permeability for nano/microparticle drugs. Here, a pinecone-inspired smart microcage with open network shells, assembled from cellulose nanofibrils (CNFs), is reported for nano/microparticle drug delivery. The approach allows the nanoarchitectured, functionalized CNFs to assemble into mechanically robust, haystack-like network shells with tunable large-through pores and polypeptide-anchored points on a large scale. Such open network shells can intelligently open/close triggered by lesion stimuli, making the therapy "always on-demand." The resulting pinecone-inspired microcages exhibit integrated properties of superior structural stability, superhydrophilicity, and pH-triggered, smart across-shell transport of emerging antimicrobial silver nanoparticles and bioactive silicate nanoplatelets (sizes of >100 nm), which enable both extraordinary anti-infection and bone regeneration. This work provides new insights into the design and development of multifunctional encapsulation and delivery carriers for medical and environmental applications.

Silver nanoparticles present high intracellular and extracellular killing against Staphylococcus aureus.

OBJECTIVES: Bone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs). METHODS: Intracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment. RESULTS: AgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 µM, along with a high intracellular killing efficacy of 76% at 371 µM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 µM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin. CONCLUSIONS: AgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.

Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering.

Achieving surface design and control of biomaterial scaffolds with nanometer- or micrometer-scaled functional films is critical to mimic the unique features of native extracellular matrices, which has significant technological implications for tissue engineering including cell-seeded scaffolds, microbioreactors, cell assembly, tissue regeneration, etc. Compared with other techniques available for surface design, layer-by-layer (LbL) self-assembly technology has attracted extensive attention because of its integrated features of simplicity, versatility, and nanoscale control. Here we present a brief overview of current state-of-the-art research related to the LbL self-assembly technique and its assembled biomaterials as scaffolds for tissue engineering. An overview of the LbL self-assembly technique, with a focus on issues associated with distinct routes and driving forces of self-assembly, is described briefly. Then, we highlight the controllable fabrication, properties, and applications of LbL self-assembly biomaterials in the forms of multilayer nanofilms, scaffold nanocoatings, and three-dimensional scaffolds to systematically demonstrate advances in LbL self-assembly in the field of tissue engineering. LbL self-assembly not only provides advances for molecular deposition but also opens avenues for the design and development of innovative biomaterials for tissue engineering.

Mechanisms Underlying Endothelin-1 Level Elevations Caused by Excessive Fluoride Exposure.

OBJECTIVE: To explore the mechanisms underlying endothelin-1 (ET-1) elevations induced by excessive fluoride exposure. METHODS: We measured serum and bone fluoride ion content and plasma ET-1 levels and compared these parameters among different groups in an animal model. We also observed morphological changes in the aorta and endothelium of rabbits. In cell experiments, human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of NaF for 24h, with or without 10 µM U0126 pretreatment for 1 h. ET-1 levels in culture fluid and intracellular reactive oxygen species (ROS) levels, as well as ET1 gene, endothelin-converting enzyme-1 (ECE-1), extracellular signal-regulating kinase 1/2 (ERK1/2), pERK1/2 expression levels and RAS activation were measured and compared among the groups. RESULTS: Plasma ET-1 levels of rabbits increased significantly in fluorinated groups compared with those in the control group. The rabbit thoracic aortas became slightly hardened in fluorinated groups compared with those in the control group, and some vacuoles were present in the endothelial cell cytoplasm of the rabbits in fluorinated groups. In our cell experiments, ET1 gene and ECE-1 expression levels in HUVECs and ET-1 expression levels in the cell culture supernatants increased significantly in some experimental groups compared with those in the control group. These trends paralleled the changes in intracellular ROS levels, RAS activation, and the pERK1/2-to-ERK1/2 ratio. After U0126 was added, ECE-1 expression and ET-1 levels decreased significantly. CONCLUSION: Excessive fluoride exposure leads to characteristic endothelial damage (vacuoles), thoracic aorta hardening, and plasma ET-1 level elevations in rabbits. In addition, the ROS-RAS-MEK1/2-pERK1/2/ERK1/2 pathway plays a crucial-and at least partial-role in ET-1 over-expression, which is promoted by excessive fluoride exposure.

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection.

BACKGROUND: Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. RESULTS: We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1-6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6-8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureus infection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. CONCLUSIONS: S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells.

Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro.

Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause "hard metal lung disease" but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure.

Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression.

Over the past two decades, fluoride effects on osteoclasts have been evaluated; however, its molecular mechanisms remain unclear. In this study, we investigated the effect of fluoride on osteoclast formation, function, and regulation using osteoclasts formed from mice bone marrow macrophages treated with the receptor activator of NF-κB ligand and macrophage colony-stimulating factor. Our data showed that fluoride levels ≤ 8 mg/L had no effect on osteoclast formation; however, it significantly reduced osteoclast resorption at 0.5 mg/L. Fluoride activity on bone resorption occurred through the inhibition of nuclear factor of active T cells (NFAT) c1 expression. Furthermore, the expression of its downstream genes, including the dendritic cell-specific transmembrane protein, c-Src, the d2 isoform of vacuolar (H+) ATPase v0 domain, matrix metalloproteinase 9, and cathepsin K were decreased, leading to impaired osteoclast acidification, reduced secretion of proteolytic enzymes, and decreased bone resorption. In summary, our results suggested that fluoride has different roles in osteoclast formation and function. Fluoride ≤ 8 mg/L did not impact osteoclast formation; however, it significantly decreased the resorption activity of newly formed osteoclasts. The molecular mechanism of fluoride action may involve inhibition of NFATc1 and its downstream genes.

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section.

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.

Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus.

The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicrobial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus. Bacterial killing assays and an infection model of osteoblasts and S. aureus were studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus. We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefazolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus. Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus. The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus. Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and intracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recurrent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens.

Biomimetic electrospun nanofibrous structures for tissue engineering.

Biomimetic nanofibrous scaffolds mimicking important features of the native extracellular matrix provide a promising strategy to restore functions or achieve favorable responses for tissue regeneration. This review provides a brief overview of current state-of-the-art research designing and using biomimetic electrospun nanofibers as scaffolds for tissue engineering. It begins with a brief introduction of electrospinning and nanofibers, with a focus on issues related to the biomimetic design aspects. The review next focuses on several typical biomimetic nanofibrous structures (e.g. aligned, aligned to random, spiral, tubular, and sheath membrane) that have great potential for tissue engineering scaffolds, and describes their fabrication, advantages, and applications in tissue engineering. The review concludes with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers.

Chaetoglobosin K inhibits tumor angiogenesis through downregulation of vascular epithelial growth factor-binding hypoxia-inducible factor 1α.

Ovarian cancer is the fifth leading cause of cancer deaths for women in America. With no known carcinogens or manageable risk factors, targeted prevention is currently unavailable. Angioprevention is a nonspecific strategy to limit the growth of solid tumors and is especially suitable for ovarian cancers. In search of angiopreventive agents, we examined chaetoglobosin K (ChK), a natural cytochalasan compound from the fungus Diplodia macrospora. We found that ChK significantly inhibits cell viability at concentrations as low as 0.5 µmol/l for A2780/CP70 ovarian cancer cells and 1.0 µmol/l for OVCAR-3 cells. ChK also significantly inhibits the secretion of key angiogenesis mediators, including Akt (which is also known as protein kinase B), hypoxia-inducible factor 1α (HIF-1α), and vascular epithelial growth factor (VEGF) by ovarian cancer cells. More importantly, ChK inhibits in-vitro and in-vivo angiogenesis induced by ovarian cancer cells and reduces the migratory capability of human umbilical vein endothelial cells. Through transfection of HIF-1α plasmids in luciferase assays, we found that ChK executes its VEGF inhibition by mediating the downregulation of HIF-1α. Furthermore, chromatin immunoprecipitation assays using the HIF-1α antibody revealed that ChK inhibits the interaction of HIF-1α with the VEGF promoter. Through transfection of Akt plasmids, we found that inhibition of HIF-1α by ChK occurs through downregulation of Akt. To our knowledge, this is the first report about the potential angioprevention of ChK. Our data suggest that this natural fungal bioactive compound effectively inhibits angiogenesis through downregulation of VEGF-binding HIF-1α and could be an effective agent for cancer treatment.

CO2 capture properties of lithium silicates with different ratios of Li2O/SiO2: an ab initio thermodynamic and experimental approach.

The lithium silicates have attracted scientific interest due to their potential use as high-temperature sorbents for CO2 capture. The electronic properties and thermodynamic stabilities of lithium silicates with different Li2O/SiO2 ratios (Li2O, Li8SiO6, Li4SiO4, Li6Si2O7, Li2SiO3, Li2Si2O5, Li2Si3O7, and α-SiO2) have been investigated by combining first-principles density functional theory with lattice phonon dynamics. All these lithium silicates examined are insulators with band-gaps larger than 4.5 eV. By decreasing the Li2O/SiO2 ratio, the first valence bandwidth of the corresponding lithium silicate increases. Additionally, by decreasing the Li2O/SiO2 ratio, the vibrational frequencies of the corresponding lithium silicates shift to higher frequencies. Based on the calculated energetic information, their CO2 absorption capabilities were extensively analyzed through thermodynamic investigations on these absorption reactions. We found that by increasing the Li2O/SiO2 ratio when going from Li2Si3O7 to Li8SiO6, the corresponding lithium silicates have higher CO2 capture capacity, higher turnover temperatures and heats of reaction, and require higher energy inputs for regeneration. Based on our experimentally measured isotherms of the CO2 chemisorption by lithium silicates, we found that the CO2 capture reactions are two-stage processes: (1) a superficial reaction to form the external shell composed of Li2CO3 and a metal oxide or lithium silicate secondary phase and (2) lithium diffusion from bulk to the surface with a simultaneous diffusion of CO2 into the shell to continue the CO2 chemisorption process. The second stage is the rate determining step for the capture process. By changing the mixing ratio of Li2O and SiO2, we can obtain different lithium silicate solids which exhibit different thermodynamic behaviors. Based on our results, three mixing scenarios are discussed to provide general guidelines for designing new CO2 sorbents to fit practical needs.

Operator-as-a-Consumer: A Novel Energy Storage Sharing Approach Under Demand Charge.

Energy storage systems (ESSs)-based demand response (DR) is an appealing way to save electricity bills for consumers under demand charge and time-of-use (TOU) price. In order to counteract the high investment cost of ESS, a novel operator-enabled ESS sharing scheme, namely, the "operator-as-a-consumer (OaaC)," is proposed and investigated in this article. In this scheme, the users and the operator form a Stackelberg game. The users send ESS orders to the operator and apply their own ESS dispatching strategies for their own purposes. Meanwhile, the operator maximizes its profit through optimal ESS sizing and scheduling, as well as pricing for the users' ESS orders. The feasibility and economic performance of OaaC are further analyzed by solving a bilevel joint optimization problem of ESS pricing, sizing, and scheduling. To make the analysis tractable, the bilevel model is first transformed into its single-level mathematical program with equilibrium constraints (MPEC) formulation and is then linearized into a mixed-integer linear programming (MILP) problem using multiple linearization methods. Case studies with actual data are utilized to demonstrate the profitability for the operator and simultaneously the ability of bill saving for the users under the proposed OaaC scheme.

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology.

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail.

Chemical Synthesis of Innovative Silver Nanohybrids with Synergistically Improved Antimicrobial Properties.

Background: The wide use of antibiotics has created challenges related to antibiotic-resistant bacteria, which have been increasingly found in recent decades. Antibiotic resistance has led to limited choices of antibiotics. Multiple old antimicrobial agents have high antimicrobial properties toward bacteria, but they unfortunately also possess high toxicity toward humans. For instance, silver (Ag) compounds were frequently used to treat tetanus and rheumatism in the 19th century and to treat colds and gonorrhea in the early 20th century. However, the high toxicity of Ag has limited its clinical use. Purpose: We aimed to reformulate Ag to reduce its toxicity toward human cells like osteoblasts and to optimize its antimicrobial properties. Results: Ag, an old antimicrobial agent, was reformulated by hybriding nanomaterials of different dimensions, and silver nanoparticles (AgNPs) of controllable sizes (95-200 nm) and varying shapes (cube, snowflake, and sphere) were synthesized on carbon nanotubes (CNTs). The obtained AgNP-CNT nanohybrids presented significantly higher killing efficacy against Staphylococcus aureus (S. aureus) compared to AgNPs at the same molar concentration and showed synergism in killing S. aureus at 0.2 and 0.4 mM. AgNPs presented significant osteoblast toxicity; in contrast, AgNP-CNT nanohybrids demonstrated significantly enhanced osteoblast viability at 0.04-0.8 mM. The killing of S. aureus by AgNP-CNT nanohybrids was fast, occurring within 15 min. Conclusion: Ag was successfully reformulated and Ag nanohybrids with various AgNP shapes on CNTs were synthesized. The nanohybrids presented significantly enhanced antimicrobial properties and significantly higher osteoblast cell viability compared to AgNPs, showing promise as an innovative antimicrobial nanomaterial for a broad range of biomedical applications.

Fluoride induced metabolic disorder of endothelial cells.

Endemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.