Global quantification of emerging and legacy per- and polyfluoroalkyl substances in indoor dust: Levels, profiles and human exposure.

This study investigated the occurrence and distribution of per- and polyfluoroalkyl substances (PFASs) in house dust samples from six regions across four continents. PFASs were detected in all indoor dust samples, with total median concentrations ranging from 17.3 to 197 ng/g. Among the thirty-one PFAS analytes, eight compounds, including emerging PFASs, exhibited high detection frequencies in house dust from all six locations. The levels of PFASs varied by region, with higher concentrations found in Adelaide (Australia), Tianjin (China), and Carbondale (United States, U.S.). Moreover, PFAS composition profiles also differed among regions. Dust from Australia and the U.S. contained high levels of 6:2 fluorotelomer phosphate ester (6:2 diPAP), while perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were predominant in other regions. Furthermore, our results indicate that socioeconomic factors impact PFAS levels. The assessment of human exposure through dust ingestion and dermal contact indicates that toddlers may experience higher exposure levels than adults. However, the hazard quotients of PFASs for both toddlers and adults were below one, indicating significant health risks are unlikely. Our study highlights the widespread occurrence of PFASs in global indoor dust and the need for continued monitoring and regulation of these chemicals.

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Induced pluripotent stem cells (iPSCs) are obtained by introducing exogenous genes or adding chemicals to the culture medium to induce somatic cell differentiation. iPSCs have the ability to differentiate into all three embryonic cell lines, similar to embryonic stem cells. iPSCs can differentiate into cardiac muscle cells through two-dimensional differentiation methods such as monolayer cell culture and co-culture, or through embryoid body and scaffold-based three-dimensional differentiation methods. In addition, the process of iPSCs differentiation into cardiac muscle cells also requires activation or inhibition of specific signaling pathways,such as Wnt, BMP, Notch signaling pathways to mimic the development of the heart in vivo. In recent years, cell suspension culture by bioreactors has been able to produce large number of iPSCs derived cardiac muscle cells (iPSC-CMs). Before transplantation it is necessary to purify iPSC-CMs through metabolic regulation or cell sorting to eliminate undifferentiated iPSCs, which may lead to teratoma formation. The transplantation methods for iPSC-CMs are mainly injection of cell suspension and transplantation of cell patches into the infarcted myocardium. Animal studies have shown that transplantation of iPSC-CMs into the infarcted myocardium can improve cardiac function. This article reviews the progress of preclinical studies on iPSC-CMs therapy for acute myocardial infarction and discusses the limitations and challenges of its clinical application to provide references for further clinical research and application.

Effects of multiple factors on particle size selectivity under artificial extreme rainfall events on simulated Gobi surface.

Understanding multiple-factor effects on particle size selectivity by extreme rainfall events in Ala-Shan Gobi desert is of great significance for better estimation of potential Asian dust emission sources. Artificial rainfall simulation experiments were used to investigate the particle size selectivity characteristics by extreme rainfall events under different rainfall intensities (20 mm h-1 and 40 mm h-1), slope gradients (3° and 15°) and gravel coverages (0, 30%, and 60%). Moreover, the relations of clay content (Clc), silt content (Sic), fine particle (< 50 µm) content (Fic) and enrichment ratio of fine particles (ER<50) with multiple factors were regressed and validated. Results show that rainfall intensity significantly (P < 0.05) affect runoff and sediment yield processes, but slope gradient was a dominant factor that changed particle size distribution (PSD). The selectivity of fine particles was higher at low rainfall intensity (20 mm h-1), gentle slope (3°) and moderate gravel coverage (30%), with ER<50 reaching 6.14, which dominate the potential Asian dust emission sources. The interaction were discussed and classified into 'Synergy' and 'Trade-off'. Clc and Fic showed negative exponential relationship with rainfall intensity and slope gradient, but positive exponential relationship with gravel coverage. While Sic and ER<50 showed negative power function relationship with rainfall intensity, slope gradient and gravel coverage. These findings could help to understand the effects of multiple factors on potential sources of Asian dust emission under extreme rainfall events in Gobi region of northwestern China and provide basic science reference for the prediction of dust emission in this region.

Spatial lipidomics and metabolomics of multicellular tumor spheroids using MALDI-2 and trapped ion mobility imaging.

Lipids and metabolites are small biological molecules that act major roles in cellular functions. Multicellular tumor spheroids (MCTS) are a highly beneficial three-dimensional cellular model for cancer research due to their ability to imitate numerous characteristics of tumor tissues. Increasing studies have performed spatial lipidomics and metabolomics in MCTS using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). However, these approaches often lack the sensitivity and specificity to offer a comprehensive characterization of lipids and metabolites within MCTS. In this study, we addressed this challenge by utilizing MALDI combined with laser-induced postionization (MALDI-2) and trapped ion mobility spectrometry (TIMS) imaging in H295R adrenocortical MCTS. Our results showed that MALDI-2 could detect more lipids and metabolites in MCTS than the traditional MALDI. TIMS data revealed a successful separation of many isomeric and isobaric ions of lipids and metabolites with different locations (e.g., proliferative region and necrotic region) within MCTS, suggesting an enhanced peak capacity for spatial lipidomics and metabolomics. To further identify these isomeric and isobaric ions, we performed MS/MS imaging experiments to compare the differences in signal intensities and spatial distributions of product ions. Our data highlight the strong potential of MALDI-2 and TIMS imaging for analyzing lipids and metabolites in MCTS, which may serve as valuable tools for numerous fields of biological and medical research.

[Study on quantitative analysis of bracket-induced nonlinear response of labio-cheek soft tissue during the orthodontic process].

In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: ① the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; ② the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.

Long-term percutaneous triclosan exposure induces thyroid damage in mice: Interpretation of toxicity mechanism from metabolic and proteomic perspectives.

Triclosan (TCS) is an antiseptic incorporated in consumer goods and personal care products that can be absorbed via the skin, raising public health concerns for its continuous detection in human biofluids and tissues. Epidemiology has associated TCS exposure with thyroid function disturbances and decreasing serum thyroid hormone (TH) levels, but the underlying mechanism remains unclear. In this study, we revealed hypothyroidism and histological alternation in the thyroid of mice with chronic percutaneous exposure to TCS, indicating a TCS-caused thyroid impairment. Subsequently, multi-omics approaches were performed to investigate the molecular mechanism of the thyroid in response to long-term dermal TCS exposure. We discovered that TCS interfered with the TH synthesis as indicated by the changes in the levels of the synthetic materials for TH (iodide, Tg, and H2O2) and affected TH release by the downregulation of lysosomal enzymes. The upregulation of glycolysis, tricarboxylic acid cycle, fatty acid, amino acid metabolism, and adenine salvage in the thyroid was also observed after TCS exposure. All these changes led to the elevation of ATP, serving as a rescue for the decreasing thyroid functions. Together, our study demonstrated TCS-induced thyroid damage and identified the interrupted pathways, providing meaningful insight into the molecular mechanisms underpinning the potential health influence of TCS in humans.

Nonphthalate Plasticizers in House Dust from Multiple Countries: An Increasing Threat to Humans.

Along with the restrictions of phthalate esters (PAEs), a variety of nonphthalate plasticizers (NPPs) have been increasingly used for industrial needs. Knowledge remains limited on the environmental occurrences, fate, and human exposure risks of many emerging NPPs. In this study, we investigated a suite of 45 NPPs along with the major PAEs in house dust from five regions in the Asia-Pacific region and the United States. The findings clearly demonstrated ubiquitous occurrences of many NPPs in the home environment, particularly acetyl tributyl citrate (ATBC), tricapryl trimellitate (TCTM), trioctyl trimellitate (TOTM), glycerol monooleate (GMO), methyl oleate (MO), and diisobutyl adipate (DiBA). The median total concentrations of NPPs ranged from 17.8 to 252 µg/g in the study regions, while the mean ratios of ΣNPPs to ΣPAEs ranged from 0.19 (Hanoi) to 0.72 (Adelaide). Spatial differences were observed not only for the chemical abundances but also for the composition profiles and the hazard quotient (HQ) prioritization of individual chemicals. Although the current exposure may unlikely cause significant health risks according to the HQ estimation, potential exposure risks cannot be overlooked, due to the lack of appropriate toxic threshold data, the existence of additional exposure pathways, and possible cocktail effects from coexisting NPPs and PAEs.

ODF2L acts as a synthetic lethal partner with WEE1 inhibition in epithelial ovarian cancer models.

WEE1 has emerged as an attractive target in epithelial ovarian cancer (EOC), but how EOC cells may alter their sensitivity to WEE1 inhibition remains unclear. Here, through a cell cycle machinery-related gene RNAi screen, we found that targeting outer dense fiber of sperm tails 2-like (ODF2L) was a synthetic lethal partner with WEE1 kinase inhibition in EOC cells. Knockdown of ODF2L robustly sensitized cells to treatment with the WEE1 inhibitor AZD1775 in EOC cell lines in vitro as well as in xenografts in vivo. Mechanistically, the increased sensitivity to WEE1 inhibition upon ODF2L loss was accompanied by accumulated DNA damage. ODF2L licensed the recruitment of PKMYT1, a functionally redundant kinase of WEE1, to the CDK1-cyclin B complex and thus restricted the activity of CDK1 when WEE1 was inhibited. Clinically, upregulation of ODF2L correlated with CDK1 activity, DNA damage levels, and sensitivity to WEE1 inhibition in patient-derived EOC cells. Moreover, ODF2L levels predicted the response to WEE1 inhibition in an EOC patient-derived xenograft model. Combination treatment with tumor-targeted lipid nanoparticles that packaged ODF2L siRNA and AZD1775 led to the synergistic attenuation of tumor growth in the ID8 ovarian cancer syngeneic mouse model. These data suggest that WEE1 inhibition is a promising precision therapeutic strategy for EOC cells expressing low levels of ODF2L.

Platinum-Resistant Ovarian Cancer Is Vulnerable to the cJUN-XRCC4 Pathway Inhibition.

DNA double-strand breaks (DSBs) caused by platinum drugs are dangerous lesions that kill cancer cells in chemotherapy. Repair of DSB by homologous recombination (HR) and nonhomologous end joining (NHEJ) is frequently associated with platinum resistance in ovarian cancer. While the role of the HR pathway and HR-targeting strategy in platinum resistance is well studied, dissecting and targeting NHEJ machinery to overcome platinum resistance in ovarian cancer remain largely unexplored. Here, through an NHEJ pathway-focused gene RNAi screen, we found that the knockdown of XRCC4 significantly sensitized cisplatin treatment in the platinum-resistant ovarian cancer cell lines. Moreover, upregulation of XRCC4 is observed in a panel of platinum-resistant cell lines relative to the parental cell lines, as well as in ovarian cancer patients with poor progression-free survival. Mechanistically, the increased sensitivity to cisplatin upon XRCC4 knockdown was caused by accumulated DNA damage. In cisplatin-resistant ovarian cancer, the JNK-cJUN complex, activated by cisplatin, translocated into the nucleus and promoted the transcription of XRCC4 to confer cisplatin resistance. Knockdown of XRCC4 or treatment of the JNK inhibitor led to the attenuation of cisplatin-resistant tumor growth in the xenograft mouse models. These data suggest targeting XRCC4 is a potential strategy for ovarian cisplatin resistance in ovarian cancer.

Systematic Bioinformatics Analysis Based on Public and Second-Generation Sequencing Transcriptome Data: A Study on the Diagnostic Value and Potential Mechanisms of Immune-Related Genes in Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases worldwide. Advances in genomics have provided new ideas for the development of novel molecular biomarkers of potential clinical value for AMI. Methods: Based on microarray data from a public database, differential analysis and functional enrichment analysis were performed to identify aberrantly expressed genes in AMI and their potential functions. CIBERSORT was used for immune landscape analysis. We also obtained whole blood samples of 3 patients with AMI and performed second-generation sequencing (SGS) analysis. Weighted gene co-expression network analysis (WGCNA) and cross-tabulation analysis identified AMI-related key genes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic power of key genes. Single-gene gene set enrichment analysis (GSEA) revealed the molecular mechanisms of diagnostic indicators. Results: A total of 53 AMI-related DEGs from a public database were obtained and found to be involved in immune cell activation, immune response regulation, and cardiac developmental processes. CIBERSORT confirmed that the immune microenvironment was altered between AMI and normal samples. A total of 77 hub genes were identified by WGCNA, and 754 DEGs were obtained from own SGS data. Seven diagnostic indicators of AMI were obtained, namely GZMA, NKG7, TBX21, TGFBR3, SMAD7, KLRC4, and KLRD1. The single-gene GSEA suggested that the diagnostic indicators seemed to be closely implicated in cell cycle, immune response, cardiac developmental, and functional regulatory processes. Conclusion: The present study provides new diagnostic indicators for AMI and further confirms the feasibility of the results of genome-wide gene expression analysis.

ROS-regulated phosphorylation of ITPKB by CAMK2G drives cisplatin resistance in ovarian cancer.

Platinum resistance accounts for much of the high mortality and morbidity associated with ovarian cancer. Identification of targets with significant clinical translational potential remains an unmet challenge. Through a high-throughput synthetical lethal screening for clinically relevant targets using 290 kinase inhibitors, we identify calcium/calmodulin-dependent protein kinase II gamma (CAMK2G) as a critical vulnerability in cisplatin-resistant ovarian cancer cells. Pharmacologic inhibition of CAMK2G significantly sensitizes ovarian cancer cells to cisplatin treatment in vitro and in vivo. Mechanistically, CAMK2G directly senses ROS, both basal and cisplatin-induced, to control the phosphorylation of ITPKB at serine 174, which directly regulates ITPKB activity to modulate cisplatin-induced ROS stress. Thereby, CAMK2G facilitates the adaptive redox homeostasis upon cisplatin treatment and drives cisplatin resistance. Clinically, upregulation of CAMK2G activity and ITPKB pS174 correlates with cisplatin resistance in human ovarian cancers. This study reveals a key kinase network consisting of CAMK2G and ITPKB for ROS sense and scavenging in ovarian cancer cells to maintain redox homeostasis, offering a potential strategy for cisplatin resistance treatment.

Severe dioxin-like compound (DLC) contamination in e-waste recycling areas: An under-recognized threat to local health.

Electrical and electronic waste (e-waste) burning and recycling activities have become one of the main emission sources of dioxin-like compounds (DLCs). Workers involved in e-waste recycling operations and residents living near e-waste recycling sites (EWRS) are exposed to high levels of DLCs. Epidemiological and experimental in vivo studies have reported a range of interconnected responses in multiple systems with DLC exposure. However, due to the compositional complexity of DLCs and difficulties in assessing mixture effects of the complex mixture of e-waste-related contaminants, there are few studies concerning human health outcomes related to DLC exposure at informal EWRS. In this paper, we have reviewed the environmental levels and body burdens of DLCs at EWRS and compared them with the levels reported to be associated with observable adverse effects to assess the health risks of DLC exposure at EWRS. In general, DLC concentrations at EWRS of many countries have been decreasing in recent years due to stricter regulations on e-waste recycling activities, but the contamination status is still severe. Comparison with available data from industrial sites and well-known highly DLC contaminated areas shows that high levels of DLCs derived from crude e-waste recycling processes lead to elevated body burdens. The DLC levels in human blood and breast milk at EWRS are higher than those reported in some epidemiological studies that are related to various health impacts. The estimated total daily intakes of DLCs for people in EWRS far exceed the WHO recommended total daily intake limit. It can be inferred that people living in EWRS with high DLC contamination have higher health risks. Therefore, more well-designed epidemiological studies are urgently needed to focus on the health effects of DLC pollution in EWRS. Continuous monitoring of the temporal trends of DLC levels in EWRS after actions is of highest importance.

MicroRNAs and their role in environmental chemical carcinogenesis.

MicroRNAs (miRNAs) are a class of small, noncoding RNA species that play crucial roles across many biological processes and in the pathogenesis of major diseases, including cancer. Recent studies suggest that the expression of miRNA is altered by certain environmental chemicals, including metals, organic pollutants, cigarette smoke, pesticides and carcinogenic drugs. In addition, extensive studies have indicated the existence and importance of miRNA in different cancers, suggesting that cancer-related miRNAs could serve as potential markers for chemically induced cancers. The altered expression of miRNA was considered to be a vital pathogenic role in xenobiotic-induced cancer development. However, the significance of miRNA in the etiology of cancer and the exact mechanisms by which environmental factors alter miRNA expression remain relatively unexplored. Hence, understanding the interaction of miRNAs with environmental chemicals will provide important information on mechanisms underlying the pathogenesis of chemically induced cancers, and effectively diagnose and treat human cancers resulting from chronic or acute carcinogen exposure. This study presents the current evidence that the miRNA deregulation induced by various chemical carcinogens, different cancers caused by environmental carcinogens and the potentially related genes in the onset or progression of cancer. For each carcinogen, the specifically expressed miRNA may be considered as the early biomarkers of the cancer process. In this review, we also summarize various target genes of the altered miRNA, oncogenes or anti-oncogenes, and the existing evidence regarding the gene regulation mechanisms of cancer caused by environmentally induced miRNA alteration. The future perspective of miRNA may become attractive targets for the diagnosis and treatment of carcinogen-induced cancer.

Air pollution and body burden of persistent organic pollutants at an electronic waste recycling area of China.

This paper reviews the concentrations of persistent organic pollutants (POPs) in atmosphere of an electronic waste (e-waste) recycling town, Guiyu, in Southeast China, focusing on polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). We assess the evidence for the association between air pollution and human body burden, to provide an indication of the severity of respiratory exposure. Compared with standards and available existing data for other areas, it clearly shows that four typical POPs, derived from recycling processes, lead to serious atmospheric pollution and heavy body burden. From published data, the estimated respiratory exposure doses of Guiyu adults and children, varied between 2.48-10.37 and 3.25-13.6 ng kg-1 body weight (bw) day-1 for PBDEs, 2.31-7.6 and 4.09-13.58 pg World Health Organization-Toxic Equivalent Quantity (WHO-TEQ) kg-1 bw day-1 for PCDD/Fs, 5.57 and 20.52 ng kg-1 bw day-1 for PCBs, and 8.59-50.01 and 31.64-184.14 ng kg-1 bw day-1 for PAHs, respectively. These results show that air pollution is more harmful to children. Furthermore, except for PBDEs, the hazard quotient (HQ) of the other three pollutants was rated more than 1 by respiratory exposure only, and all of them are at risk of carcinogenesis. So we speculate these pollutants enter the body mainly through air inhalation, making respiratory exposure may be more important than dietary exposure in the Guiyu e-waste recycling area. Effective management policies and remediation techniques are urgently needed to prevent the deterioration of ambient air quality in the e-waste recycling area.

Efficient generation of transgene- and feeder-free induced pluripotent stem cells from human dental mesenchymal stem cells and their chemically defined differentiation into cardiomyocytes.

Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application. Moreover, induced PSCs showed the capacity of self-renewal and differentiation into cardiac myocytes. We have achieved the differentiation of hiPSCs to cardiomyocytes lineage under serum and feeder-free conditions, using a chemically defined medium CDM3. In CDM3, hiPSCs differentiation is highly generating cardiomyocytes. The results showed this protocol produced contractile sheets of up to 97.2% TNNT2 cardiomyocytes after purification. Furthermore, derived hiPSCs differentiated to mature cells of the three embryonic germ layers in vivo and in vitro of beating cardiomyocytes. The above whole protocol enables the generation of large scale of highly pure cardiomyocytes as needed for cellular therapy.

Characterization of microRNAs expression profiles in human dental-derived pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) technology provides a powerful means to generate and regenerate unlimited pluripotent stem cells directly from body tissue cells. Stem cells from apical papilla (SCAP) and Dental pulp stem cells (DPSCs) are present in 'cell-rich zones' within the dental pulp region, which are capable of regenerating pulp and dentin tissues in vivo. In this study, we investigated the difference of miRNAs expression in SCAPs and DPSCs before and after the reprogramming. Using miRNA microarray, 134 and 265 differentially expressed miRNAs in DPSCs- and SCAP-iPSCs were up-regulated compared to these before reprogramming. 117 specific miRNAs with enhanced more than 2-fold were identified in both DPSCs- and SCAP-iPSCs. Among the co-regulated miRNAs, miR-19a-3p, miR-92b-3p and miR-130b-3p showed the maximum difference, which had involvement in the cell cycle, TGF beta signaling pathway and epithelial mesenchymal transition. Using qRT-PCR analysis, the expression of miR-19a-3p, miR-92b-3p and miR-130b-3p indicated substantial increases in DPSCs-iPSCs and SCAP-iPSCs. The findings suggest that miRNAs play a part in the difference between DPSCs-iPSCs and DPSCs, as well as between SCAP-iPSCs and SCAP. The variation of miRNA expression in reprogrammed dental-derived pluripotent stem cells revealed different characteristics induced by iPSC generation.

Mechanism of Formation and Stabilization of Nanoparticles Produced by Heating Electrostatic Complexes of WPI-Dextran Conjugate and Chondroitin Sulfate.

Protein conformational changes were demonstrated in biopolymer nanoparticles, and molecular forces were studied to elucidate the formation and stabilization mechanism of biopolymer nanoparticles. The biopolymer nanoparticles were prepared by heating electrostatic complexes of whey protein isolate (WPI)-dextran conjugate (WD) and chondroitin sulfate (ChS) above the denaturation temperature and near the isoelectric point of WPI. The internal characteristics of biopolymer nanoparticles were analyzed by several spectroscopic techniques. Results showed that grafted dextran significantly (p < 0.05) prevented the formation of large aggregates of WD dispersion during heat treatment. However, heat treatment slightly induced the hydrophobicity changes of the microenvironment around fluorophores of WD. ChS electrostatic interaction with WD changed the fluorescence intensity of WD regardless of heat treatment. Far-UV circular dichroism (CD) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopies confirmed that glycosylation and ionic polysaccharide did not significantly cause protein conformational changes in WD and ChS (WDC) during heat treatment. In addition, hydrophobic bonds were the major molecular force for the formation and stabilization of biopolymer nanoparticles. However, hydrogen bonds slightly influenced their formation and stabilization. Ionic bonds only promoted the formation of biopolymer nanoparticles, while disulfide bonds partly contributed to their stability. This work will be beneficial to understand protein conformational changes and molecular forces in biopolymer nanoparticles, and to prepare the stable biopolymer nanoparticles from heating electrostatic complexes of native or glycosylated protein and polysaccharide.

Stable nanoparticles prepared by heating electrostatic complexes of whey protein isolate-dextran conjugate and chondroitin sulfate.

A simple and green method was developed for preparing the stable biopolymer nanoparticles with pH and salt resistance. The method involved the macromolecular crowding Maillard process and heat-induced gelation process. The conjugates of whey protein isolate (WPI) and dextran were produced by Maillard reaction. The nanoparticles were fabricated by heating electrostatic complexes of WPI-dextran conjugate and chondroitin sulfate (ChS) above the denaturation temperature and near the isoelectric point of WPI. Then, the nanoparticles were characterized by spectrophotometry, dynamic laser scattering, zeta potential, transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. Results showed that the nanoparticles were stable in the pH range from 1.0 to 8.0 and in the presence of high salt concentration of 200 mM NaCl. WPI-dextran conjugate, WPI, and ChS were assembled into the nanoparticles with dextran conjugated to WPI/ChS shell and WPI/ChS core. The repulsive steric interactions, from both dextran covalently conjugated to WPI and ChS electrostatically interacted with WPI, were the major formation mechanism of the stable nanoparticles. As a nutrient model, lutein could be effectively encapsulated into the nanoparticles. Additionally, the nanoparticles exhibited a spherical shape and homogeneous size distribution regardless of lutein loading. The results suggested that the stable nanoparticles from proteins and strong polyelectrolyte polysaccharides would be used as a promising target delivery system for hydrophobic nutrients and drugs at physiological pH and salt conditions.