Exposure to polystyrene nanoplastics induces abnormal activation of innate immunity via the cGAS-STING pathway.

Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.

Therapeutic strategies for drug-resistant Pseudomonas aeruginosa: Metal and metal oxide nanoparticles.

Pseudomonas aeruginosa (PA) is a widely prevalent opportunistic pathogen. Multiple resistant strains of PA have emerged from excessive or inappropriate use of antibiotics, making their eradication increasingly difficult. Therefore, the search for highly efficient and secure novel antimicrobial agents is crucial. According to reports, there is an increasing exploration of nanometals for antibacterial purposes. The antibacterial mechanisms involving the nanomaterials themselves, the release of ions, and the induced oxidative stress causing leakage and damage to biomolecules are widely accepted. Additionally, the study of the cytotoxicity of metal nanoparticles is crucial for their antibacterial applications. This article summarizes the types of metal nanomaterials and metal oxide nanomaterials that can be used against PA, their respective unique antibacterial mechanisms, cytotoxicity, and efforts made to improve antibacterial performance and reduce toxicity, including combination therapy with other materials and antibiotics, as well as green synthesis approaches.

Analysis of risk factors for community-acquired Clostridioides difficile diarrhea in children: a case-control study in Chenzhou, China.

Background: Most previous studies on Clostridium difficile infection (CDI) mainly focused on adults with underlying diseases or critical illnesses. However, the number of CDI cases in children has also significantly increased, especially the growth of community-acquired CDI, which has attracted attention. This study was conducted to examine the toxin gene characteristics and the risk factors associated with community-acquired CDI (CA-CDI) in children with diarrhea. Methods: Children with diarrhea before admission or within 48 hours of hospitalization were included in the study. Stool samples were collected from children with community-acquired diarrhea who were treated at the Children's Hospital of the First People's Hospital of Chenzhou, China from June of 2021 to June of 2022. Fluorescence real-time polymerase chain reaction was utilized to detect Clostridioides difficile (CD) toxins A (tcdA) and B (tcdB) genes as well as binary toxin gene A (cdtA) and B (cdtB) in the specimens cultured for CD. Each child with CA-CDI was matched with four control children of the same sex, age, and place of residence. Necessary clinical data were extracted from the hospital's electronic medical record system. Then, a multivariate conditional logistic regression analysis was applied to identify potential risk factors for CA-CDI. Results: Sixteen (8.3%) of the 193 stool specimens who tested positive for CD were selected for the case group, and their matching 64 control patients were in the study cohort. The breakdown of the CD genotypes of the 16 positive cases were follows: 14 (tcdA+ and tcdB+) (7.25%) and 2 (tcdA+ and tcdB-) (1.04%). The cdtA and cdtB binary toxin genes were negative in all. The results of multivariate conditional logistic regression analysis identified antibiotic use within the previous month [odds ratio (OR) =5.13; 95% confidence interval (CI): 1.65-15.91] and non-breastfeeding (OR =4.89; 95% CI: 1.11-21.53) as independent risk factors for CDI in pediatric patients experiencing community-acquired diarrhea. Conclusions: Children who had been treated with antibiotics and not breastfed were more susceptible to CDI. Therefore, in order to prevent and to control the spread of CD infection, being prudent to the aforementioned high-risk factors is strongly advocated in clinical practice.

Metabolomics reveals that PS-NPs promote lung injury by regulating prostaglandin B1 through the cGAS-STING pathway.

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 µg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.

Micro- and macro-changes in early-stage type 2 diabetes mellitus without cognitive impairment: a diffusion tensor imaging (DTI) and surface-based morphometry (SBM) study.

Introduction: Brain structure and function changes are considered major brain damages in type 2 diabetes mellitus (T2DM), which likely has a close relationship with cognitive impairment. Many previous studies have shown by using brain structural and functional magnetic resonance imaging (MRI) methods that brain white and gray matter are damaged in T2DM, leading to cognitive impairment. Researches neglected patients of T2DM without cognitive dysfunction might also have brain changes. Methods: In this study, subjects with early stage T2DM with no cognitive dysfunction were enrolled to detect brain damages using the tract-based spatial statistics analysis (TBSS) method to demonstrate white matter (WM) micro changes and surface-based morphometry (SBM) method to assess cerebral cortex macro changes. Results: The whole-brain TBSS analysis revealed that there were no statistically significant changes in fractional anisotropy (FA) and mean diffusivity (MD), but the FA declined in some area of cerebral WM (p < 0.1). The SBM results showed no changes in cortical thickness (CT), cortical volume (CV), surface area (SA), and cortical sulcal curve (CSC) between these two groups, but pial local gyration index (LGI) was decreased in the precuneus (-log10, p = -3.327). Discussion: In conclusion, early stage T2DM patients without cognitive impairment had brain micro and macro structural damages, suggesting the potential use of MRI as an imaging marker to detect brain changes in early stage T2DM, which could not be observed and assessed clinically.

Aptamer-AuNP-conjugated carboxymethyl chitosan-functionalized graphene oxide for colorimetric identification of Salmonella typhimurium.

A novel aptamer-AuNP-conjugated carboxymethyl chitosan-functionalized graphene oxide (CMC/GO@Apt-Au NP) probe was for the first time developed for the determination of Salmonella typhimurium (S. typhimurium). Owing to the conformational change of the aptamers in the presence of S. typhimurium, the Au NPs, which were pre-adsorbed on the aptamers through van der Waals forces, were released into the solution phase and induced the color change of the solution. As a result, S. typhimurium ranging from 102 to 107 CFU/mL was successfully identified using the designed assay with a limit of detection (LOD) of 10 CFU/mL. This low detection level allowed the sensitive recognition of S. typhimurium in milk samples within 40 min without sample pretreatment, a conclusion that agreed well with the traditional plate counting method. The developed method not only provides a rapid way for the determination of S. typhimurium with simplicity and sensitivity but also shows potential universality in the quantification of other pathogenic microorganisms.

Apparent diffusion coefficient histogram analysis for differentiating solid ovarian tumors.

Objective: To evaluate the utility of apparent diffusion coefficient (ADC) histogram analysis to differentiate between three types of solid ovarian tumors: granulosa cell tumors (GCTs) of the ovary, ovarian fibromas, and high-grade serous ovarian carcinomas (HGSOCs). Methods: The medical records of 11 patients with GCTs of the ovary (regions of interest [ROI-cs], 137), 61 patients with ovarian fibromas (ROI-cs, 161), and 14 patients with HGSOCs (ROI-cs, 113) confirmed at surgery and histology who underwent diffusion-weighted imaging were retrospectively reviewed. Histogram parameters of ADC maps (ADCmean, ADCmax, ADCmin) were estimated and compared using the Kruskal-WallisH test and Mann-Whitney U test. The area under the curve of receiver operating characteristic curves was used to assess the diagnostic performance of ADC parameters for solid ovarian tumors. Results: There were significant differences in ADCmean, ADCmax and ADCmin values between GCTs of the ovary, ovarian fibromas, and HGSOCs. The cutoff ADCmean value for differentiating a GCT of the ovary from an ovarian fibroma was 0.95×10-3 mm2/s, for differentiating a GCT of the ovary from an HGSOC was 0.69×10-3 mm2/s, and for differentiating an ovarian fibroma from an HGSOC was 1.24×10-3 mm2/s. Conclusion: ADCmean derived from ADC histogram analysis provided quantitative information that allowed accurate differentiation of GCTs of the ovary, ovarian fibromas, and HGSOCs before surgery.

miR-1 Targeted Downregulation of Bcl-2 Increases Chemosensitivity of Lung Cancer Cells.

Objective: To investigate the expression of B cell lymphoma-2 (Bcl-2) in lung cancer cells and the effect of the miR-1/Bcl-2 axis on the chemosensitivity of lung cancer. Materials and Methods: Real-time quantitative PCR and western blotting were used to detect the expression of Bcl-2 in human embryonic lung fibroblasts and lung cancer cells. The effects of siRNA directed against Bcl-2, in lung cancer tissue samples was detected by immunohistochemistry; these results were used to develop prognostic models. Bioinformatic analyses, dual luciferase reporter gene technology, and western blotting technology were used to explore the targeted regulation of miR-1 on bcl-2. The effect of miR-1 on the chemosensitivity of lung cancer cells was measured using the MTT assay. Results: Compared with human embryonic lung fibroblasts, Bcl-2 was highly expressed in the lung cancer cells, especially in H460 cells. After silencing Bcl-2 with siRNA, the sensitivity of the cells to cisplatin (CDDP) increased. Immunohistochemical results and prognostic analysis revealed that high Bcl-2 expression in lung cancer tissues was negatively correlated with prognosis of lung cancer patients; A dual luciferase reporter assay combined with western blotting confirmed that miR-1 can bind to the Bcl-23' UTR region and regulate its expression. Overexpression of miR-1 in lung cancer cells (H460 and A549) increased the sensitivity of these cells to CDDP. Conclusion: Bcl-2 is upregulated in lung cancer cells, which is negatively correlated with the patient prognosis. miR-1 affects the chemosensitivity of lung cancer cells by targeting Bcl-2. These data should provide a theoretical basis for refining the molecular mechanisms of chemoresistance in lung cancer.

The research of aptamer biosensor technologies for detection of microorganism.

The activities and transmissions of microorganisms are closely related to human, and all kinds of diseases caused by pathogenic microorganisms have attracted attention in the world and brought many challenges to human health and public health. The traditional microbial detection technologies have characteristics of longer detection cycle and complicated processes, therefore, which can no longer meet the detection requirements in the field of public health. At present, it is the focus to develop and design a novel, rapid, and simple microbial detection method in the field of public health. Herein, this article summarized the development of aptamer biosensor technologies for detection of microorganism in the aspect of bacteria, viruses, and toxins in detail, including optical aptamer sensors such as fluorometry and colorimetry, electrochemical aptamer sensors, and other technologies combined with aptamer. KEY POINTS: • Aptamer biosensor is a good platform for microbial detection. • Aptamer biosensors include optical sensors and electrochemical sensors. • Aptamer sensors have been widely used in the detection of bacteria, viruses, and other microorganisms.

Optimization on preparation of Fe3O4/chitosan as potential matrix material for the removal of microcystin-LR and its evaluation of adsorption properties.

Adsorbent Fe3O4/chitosan was successfully synthesized for the removal of microcystin-LR and characterized by Scanning electron microscope, Fourier transform infra-red, thermogravimetric analysis and vibrating sample magnetometer. The effects of reaction conditions, including pH, temperature and ratio of Fe3O4 to chitosan on microcystin-LR adsorption capacity were investigated by the Box-Behnken response surface methodology design, and the optimal adsorption conditions were determined. The adsorption properties of microcystin-LR were examined by adsorption kinetics, isothermal and thermodynamics experiments. The results demonstrated that Fe3O4/chitosan was successfully prepared and the maximum adsorption capacity of microcystin-LR was under optimum conditions in which pH value was 5.53, temperature was 40 °C and the ratio of Fe3O4 to chitosan was 1:1.39. The data revealed that kinetics was fitted well with the pseudo-second-order model, Langmuir isotherm model was more appropriate for describing than the Freundlich isotherm model and the adsorption of microcystin-LR was a spontaneous process. The material maintained good adsorption capacity after five cycles. The results suggested that Fe3O4/chitosan was an efficient and low-cost adsorbent for removing microcystin-LR from polluted water.

A composite prepared from carboxymethyl chitosan and aptamer-modified gold nanoparticles for the colorimetric determination of Salmonella typhimurium.

An aptamer-based assay is described for the determination of Salmonella typhimurium (S. typh). Carboxymethyl chitosan was loaded with amino-modified aptamer against S. typh, and then adsorbed on gold nanoparticles by electrostatic interaction to form a composite that acts as the molecular recognition element. In the presence of S. typh, it will be bound by the aptamer, and this changes the structure of the recognition element. On addition of salt solution, the gold nanoparticles agglomerate so that the color of the solution changes from red to blue. S. typh can be detected via measurement of the absorbance at 550 nm. Absorbance increases linearly with the logarithm of the S. typh concentration in the range from 100 to 109 cfu·mL-1. The limit of detection is 16 cfu·mL-1. The specificity and practicability of the assay were evaluated. The recoveries of S. typh from spiked milk samples are between 92.4 and 97.2%. The analytical results are basically consistent with those of a plate counting method. Graphical abstract Schematic representation of the colorimetric assay for Salmonella typhimuium (S. typh) using carboxymethyl chitosan (CMCS)-aptamer (Apt)-gold nanoparticles (AuNPs) composites.

Efficient removal of Pb(II) from aqueous solution by a novel ion imprinted magnetic biosorbent: Adsorption kinetics and mechanisms.

It is vital to understand the adsorption mechanisms and identify the adsorption kinetics when applying an adsorbent to remove heavy metals from aqueous solution. A Pb(II) imprinted magnetic biosorbent (Pb(II)-IMB) was developed for the removal of Pb2+ via lead ion imprinting technology and crosslinking reactions among chitosan (CTS), Serratia marcescens and Fe3O4. The effect of different parameters such as solution pH, adsorbent dosage, selectivity sorption and desorption were investigated on the absorption of lead ion by Pb(II)-IMB. The adsorbent was characterized by a Brunauer-Emmett Teller (BET) analysis, X-ray diffraction (XRD), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The adsorption kinetics, equilibrium and thermodynamics of Pb(II)-IMB for Pb(II) were studied. The results of the abovementioned analyses showed that the adsorption kinetic process fit well with the second-order equation. The adsorption isotherm process of Pb(II) on the Pb(II)-IMB was closely related to the Langmuir model. Thermodynamic studies suggested the spontaneous and endothermic nature of adsorption of Pb(II) by Pb(II)-IMB. The adsorption mechanism of Pb(II)-IMB was studied by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results indicated that the nitrogen in the amino group and the oxygen in the hydroxyl group of Pb(II)-IMB were coordination atoms.

A novel lead-ion-imprinted magnetic biosorbent: preparation, optimization and characterization.

A novel biological material with high adsorption capacity and good selectivity for Pb2+ was synthesized. Response surface methodology was utilized for the optimization of the variables during the synthesis. The synthesized biosorbent was characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The optimized preparation condition for lead-ion-imprinted magnetic biosorbent (Pb(II)-IMB) was obtained (0.19 g chitosan (CTS), 0.43 g magnetic Fe3O4 and 2.11 mL/gCTS of epichlorohydrin). The highest value for the removal of lead ion was estimated to be 86.85%, with an absorption capacity of 69.48 mg/g. The characterization results indicated that Pb(II)-IMB was rich in adsorbable groups to adsorb metal ions. Because of the magnetic property of the synthesized products, it can be separated from the water easily. The relative selectivity coefficients of Pb(II)-IMB for Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Ni(II) were 2.32, 2.20 and 2.05 times higher than the non-imprinted magnetic biosorbent, respectively. Pb(II)-IMB could be reused at least five times with only ∼13% loss. These results suggested that Pb(II)-IMB was a new, efficient and low-cost material for removing Pb(II) from wastewater.

Optimization of Synthesis and Modification of ZnSe/ZnS Quantum Dots for Fluorescence Detection of Escherichia coil.

This study prepared an innovative 3-mercaptopropionic acid modified ZnSe/ZnS core/shell quantum dots (MPA-ZnSe/ZnS QDs), and established a rapid fluorescence method to detect the E. coli cells count by using MPA-ZnSe/ZnS QDs as fluorescence probe. The formulation variables and process were optimized using the response surface methodology (RSM). Fluorescence microscopy was used to obtain fluorescence microscope images of MPA-ZnSe/ZnS QDs that bind to bacteria. The fluorescence peak intensity increases with increasing cells count in the range of 101-108 CFU/mL. Compared with the traditional based on fluorescent detection methods, this method is more convenient and useful in the bacterial count determination.

Optimization of a novel chelerythrine-loaded magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid system and evaluation of its anti-tumour activities.

OBJECTIVES: A novel magnetic targeting anti-tumour drug delivery system (Fe3 O4 /KCTS-CHE) was designed using magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid (Fe3 O4 /KCTS) as carrier and chelerythrine (CHE) as an anti-tumour drug model. Moreover, the anti-tumour activities and mechanisms of Fe3 O4 /KCTS-CHE were investigated. METHODS: The preparation conditions of Fe3 O4 /KCTS-CHE microspheres were optimized by response surface methodology (RSM). The CHE drug release kinetics was evaluated by fitting the experimental data to standard release equations. The inhibitive activities of Fe3 O4 /KCTS-CHE microspheres against the HepG2 cells were estimated using MTT assay in vitro, and the mechanisms were studied using Hoechst 33258 staining. KEY FINDINGS: The optimum preparation conditions were 11.68 : 1 for Fe3 O4 /KCTS:CHE ratio, 4 : 1 for oil/water ratio and 50.03 min for the ultrasonic time. The drug loading content and entrapment efficiency under the optimal conditions were 23.3% and 50.9%. The best fit was Higuchi model for the microspheres. The inhibitive rate on HepG2 cells of Fe3 O4 /KCTS-CHE nanoparticles varied from 30.19 ± 2.64% to 70.46 ± 6.42% at different concentrations from 50 to 400 mg/l in 72 h. CONCLUSION: Fe3 O4 /KCTS-CHE exhibited effective anti-tumour activities against the HepG2 cells and induced cell apoptosis in HepG2 cells. Fe3 O4 /KCTS-CHE possess a high drug loading efficiency and entrapment efficiency, which are a new matrix for controlling release of drugs and a promising candidate for targeted drug delivery.

Nonstructural protein-1 of respiratory syncytial virus regulates HOX gene expression through interacting with histone.

Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, constitutes an important risk factor for the development of subsequent asthma. In searching for its mechanism, the present study was designed to screen the interacting proteins of two important nonstructural (NS) proteins in human BECs. The subcellular localization and the effects of NS on HOX gene expression were also examined. The results showed that NS1 was distributed throughout the nucleus and cytoplasm, while NS2 was mainly distributed in cytoplasm of BECs. NS1 interacted specifically with host histone H2BD, inducing histone ubiquitination and subsequent HOX gene expression. In conclusion, the results of the present study indicated that RSV NS-1 induces HOX gene expression, through histone ubiquitination in a BEC cell line, which may provide a novel conception for understanding the relationship between severe RSV bronchiolitis during early life and the development of subsequent asthma.