Research progress in the development of 3D skin models and their application to in vitro skin irritation testing.

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.

Combined association of urinary volatile organic compounds with chronic bronchitis and emphysema among adults in NHANES 2011-2014: The mediating role of inflammation.

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weight quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.

Advances in Engineered Nano-Biosensors for Bacteria Diagnosis and Multidrug Resistance Inhibition.

Bacterial infections continue to pose a significant global health challenge, with the emergence of multidrug-resistant (MDR) bacteria and biofilms further complicating treatment options. The rise of pan-resistant bacteria, coupled with the slow development of new antibiotics, highlights the urgent need for new therapeutic strategies. Nanotechnology-based biosensors offer fast, specific, sensitive, and selective methods for detecting and treating bacteria; hence, it is a promising approach for the diagnosis and treatment of MDR bacteria. Through mechanisms, such as destructive bacterial cell membranes, suppression of efflux pumps, and generation of reactive oxygen species, nanotechnology effectively combats bacterial resistance and biofilms. Nano-biosensors and related technology have demonstrated their importance in bacteria diagnosis and treatment, providing innovative ideas for MDR inhibition. This review focuses on multiple nanotechnology approaches in targeting MDR bacteria and eliminating antimicrobial biofilms, highlighting nano-biosensors via photodynamics-based biosensors, eletrochemistry biosensors, acoustic-dynamics sensors, and so on. Furthermore, the major challenges, opportunities of multi-physical-field biometrics-based biosensors, and relevant nanotechnology in MDR bacterial theranostics are also discussed. Overall, this review provides insights and scientific references to harness the comprehensive and diverse capabilities of nano-biosensors for precise bacteria theranostics and MDR inhibition.

Inhalation exposure to polystyrene nanoplastics induces chronic obstructive pulmonary disease-like lung injury in mice through multi-dimensional assessment.

Nanoplastics are widely distributed in indoor and outdoor air and can be easily inhaled into human lungs. However, limited studies have investigated the impact of nanoplastics on inhalation toxicities, especially on the initiation and progression of chronic obstructive pulmonary disease (COPD). To fill the gap, the present study used oronasal aspiration to develop mice models. Mice were exposed to polystyrene nanoplastics (PS-NPs) at three concentrations, as well as the corresponding controls, for acute, subacute, and subchronic exposure. As a result, PS-NPs could accumulate in exposed mice lungs and influence lung organ coefficient. Besides, PS-NPs induced local and systemic oxidative stress, inflammation, and protease-antiprotease imbalance, resulting in decreased respiratory function and COPD-like lesions. Meanwhile, PS-NPs could trigger the subcellular mechanism to promote COPD development by causing mitochondrial dysfunctions and endoplasmic reticulum (ER) stress. Mechanistically, ferroptosis played an important role in the COPD-like lung injury induced by PS-NPs. In summary, the present study comprehensively and systematically indicates that PS-NPs can damage human respiratory health and increase the risk for COPD.

HIF-1α/m6A/NF-κB/CCL3 axis-mediated immunosurveillance participates in low level benzene-related erythrohematopoietic development toxicity.

Defective erythropoiesis is one of the causes of anemia and leukemia. However, the mechanisms underlying defective erythropoiesis under a low-dose environment of benzene are poorly understood. In the present study, multiple omics (transcriptomics and metabolomics) and methods from epidemiology to experimental biology (e.g., benzene-induced (WT and HIF-1α + ) mouse, hiPSC-derived HSPCs) were used. Here, we showed that erythropoiesis is more easily impacted than other blood cells, and the process is reversible, which involves HIF-1 and NF-kB signaling pathways in low-level benzene exposure workers. Decreased HIF-1α expression in benzene-induced mouse bone marrow resulted in DNA damage, senescence, and apoptosis in BMCs and HSCs, causing disturbances in iron homeostasis and erythropoiesis. We further revealed that HIF-1α mediates CCL3/macrophage-related immunosurveillance against benzene-induced senescent and damaged cells and contributes to iron homeostasis. Mechanistically, we showed that m6A modification is essential in this process. Benzene-induced depletion of m6A promotes the mRNA stability of gene NFKBIA and regulates the NF-κB/CCL3 pathway, which is regulated by HIF-1α/METTL3/YTHDF2. Overall, our results identified an unidentified role for HIF-1α, m6A, and the NF-kB signaling machinery in erythroid progenitor cells, suggesting that HIF-1α/METTL3/YTHDF2-m6A/NF-κB/CCL3 axis may be a potential prevention and therapeutic target for chronic exposure of humans to benzene-associated anemia and leukemia.

Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis.

The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs-induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS-NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 µg/day). Results showed that inhaled PS-NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time-dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-ß, α-SMA, and Col1a1 identified that inhaled PS-NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that ferroptosis was involved in PS-NPs-induced liver hepatotoxicity, and key features of ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of ferroptosis in PS-NPs-induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS-NPs on the liver, identified that continuous inhaled PS-NPs could cause liver injury and fibrosis, and PS-NPs- ferroptosis provided a novel mechanistic explanation.

Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury.

Nanoplastics are a common type of contaminant in the air. However, no investigations have focused on the toxic mechanism of lung injury induced by nanoplastic exposure. In the present study, polystyrene nanoplastics (PS-NPs) caused ferroptosis in lung epithelial cells, which could be alleviated by ferrostatin-1, deferoxamine, and N-acetylcysteine. Further investigation found that PS-NPs disturbed mitochondrial structure and function and triggered autophagy. Mechanistically, oxidative stress-derived mitochondrial damage contributed to ferroptosis, and autophagy-dependent ferritinophagy was a pivotal intermediate link, resulting in ferritin degradation and iron ion release. Furthermore, inhibition of ferroptosis using ferrostatin-1 alleviated pulmonary and systemic toxicity to reverse the mouse lung injury induced by PS-NPs inhalation. Most importantly, the lung-on-a-chip was further used to clarify the role of ferroptosis in the PS-NPs-induced lung injury by visualizing the ferroptosis, oxidative stress, and alveolar-capillary barrier dysfunction at the organ level. In summary, our study indicated that ferroptosis was an important mechanism for nanoplastics-induced lung injury through different lung cells, mouse inhalation models, and three-dimensional-based lung-on-a-chip, providing an insightful reference for pulmonary toxicity assessment of nanoplastics.

Multi-dimensional evaluation of cardiotoxicity in mice following respiratory exposure to polystyrene nanoplastics.

BACKGROUND: Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. RESULTS: Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. CONCLUSION: The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.

Facile and Stable CuInO2 Nanoparticles for Efficient Electrochemical CO2 Reduction.

Searching for electrocatalysts for the electrochemical CO2 reduction reaction (e-CO2RR) with high selectivity and stability remains a significant challenge. In this study, we design a Cu-CuInO2 composite with stable states of Cu0/Cu+ by electrochemically depositing indium onto CuCl-decorated Cu foil. The catalyst displays superior selectivity toward the CO product, with a maximal Faraday efficiency of 89% at -0.9 V vs the reversible hydrogen electrode, and maintains impressive stability up to 27 h with a retention rate of >76% in Faraday efficiency. Our systematical characterizations reveal that the catalyst's high performance is attributed to CuInO2 nanoparticles. First-principles calculations further confirm that CuInO2(012) is more conducive to CO generation than Cu(111) under applied potential and presents a higher energy barrier than Cu(111) for the hydrogen evolution reaction. These theoretical predictions are consistent with our experimental observations, suggesting that CuInO2 nanoparticles offer a facile catalyst with a high selectivity and stability for e-CO2RR.

Metabolic risk factors link unhealthy lifestyles to the risk of colorectal polyps in China.

Colorectal cancer is the second leading cause of global cancer-related deaths, and its precursor lesions are colorectal polyps (CAP). The study aimed to explore the effect of combinations of unhealthy lifestyles on CAP and investigate the mediation role of metabolic disorder in this process. A total of 1299 adults were recruited from a hospital in Jiangsu, China, including 811 cases and 488 adults without diseases. The information on demographic characteristics and lifestyles was collected through questionnaires and the medical record system. Serum biochemical parameters were determined using the automatic biochemical analyzer. Adjusted regression analysis showed that unhealthy lifestyles, including smoking, overnight meals, daily water intake, staying up late, and exercise associated with the risk of CAP. Furthermore, metabolic biomarkers, including BMI, triglycerides, and uric acid, were associated with the risk of CAP. Also, unhealthy lifestyle scores were positively associated with BMI, triglycerides, and CAP. The mediation effect of metabolic biomarkers, such as BMI and triglycerides on the association of unhealthy lifestyle scores with CAP was significant. Available data demonstrate the adverse effect of combinations of unhealthy lifestyle factors on CAP, and metabolic disorders to potentially mediate the association of unhealthy lifestyles with the risk of CAP.

m6A modification and its role in neural development and neurological diseases.

N6-methyladenosine (m6A) methylation, the most prevalent post-transcriptional modification in eukaryotes, represents a highly dynamic and reversible process that is regulated by m6A methyltransferases, m6A demethylases and RNA-binding proteins during RNA metabolism, which affects RNA function. Notably, m6A modification is significantly enriched in the brain and exerts regulatory roles in neurogenesis and neurodevelopment through various mechanisms, further influencing the occurrence and progression of neurological disorders. This study systematically summarizes and discusses the latest findings on common m6A regulators, examining their expression, function and mechanisms in neurodevelopment and neurological diseases. Additionally, we explore the potential of m6A modification in diagnosing and treating neurological disorders, aiming to provide new insights into the molecular mechanisms and potential therapeutic strategies for neurological disorders.

Co-exposure to Fe, Zn, and Cu induced neuronal ferroptosis with associated lipid metabolism disorder via the ERK/cPLA2/AA pathway.

Excessive amounts of iron (Fe), zinc (Zn), and copper (Cu) can be toxic to neuronal cells, even though these are essential trace elements for animals and humans. However, the precise mechanisms underlying the neurotoxicity of exposure to mixtures of Fe, Zn, and Cu are still mostly unclear. The research aimed to investigate the influence of co-exposure to iron, zinc and copper and the related mechanisms in HT22 murine hippocampal neuronal cells. Intracellular metal content, markers of oxidative damage, and biomarkers of ferroptosis were respectively detected. Afterward, metabolomic analyses were performed to obtain a comprehensive understanding of the metal mixtures on metabolism, and the functions of key enzymes on metabolic pathways were validated. The results showed that metal co-exposure resulted in cellular iron overload and increased lipid peroxidation, accompanied by significant pathological damage and mitochondrial abnormalities in HT22 cells. Meanwhile, it was found that GSH depletion, decreased GPX4, and increased expression of the lipid metabolism gene ACSL4 play important roles in ferroptosis induced by metal mixture. Further, metabolomic analysis revealed metal co-exposure induced significant alterations in metabolite levels, especially in the glycerophospholipid metabolism pathway and the arachidonic acid metabolism pathway. The levels of cPLA2 and its metabolite, arachidonic acid, were significantly increased after metal co-exposure. Then, inhibition of cPLA2 decreased the level of arachidonic acid and attenuated ferroptosis in neuronal cells. Collectively, our findings unveiled ferroptosis induced by metal co-exposure associated with crucial molecular changes in neuronal cells, providing a novel perspective on the comprehensive toxicity risk assessment of metal mixtures.

Di(2-ethylhexyl) phthalate induces reproductive toxicity and transgenerational reproductive aging in Caenorhabditis elegans.

With the large-scale production and use of plastic products, the global plastic pollution problem is becoming more and more serious. The plasticizer di (2-ethylhexyl) phthalate (DEHP), which is widely used in the production of plastics, has caused great concern for the health of the population. Exposure of organisms to DEHP can cause a variety of health damage, of which reproductive system damage is an important part. At present, there are still few studies on DEHP in reproductive aging, and it is of great significance to explore the role of DEHP in promoting reproductive aging and its underlying mechanism. In this study, the model organism Caenorhabditis elegans (C. elegans) was used to preliminarily explore the mechanism of DEHP-induced female reproductive senescence. The results showed that DEHP reduced the number of offspring and gonad area of C. elegans, resulting in shortened reproductive and life span, abnormal phenotypes in somatic gonad structure including the Emo phenotype, the BOW phenotype, a twisted gonad arm, and atrophied oocytes. Biochemical studies showed that DEHP promoted oxidative stress and autophagy in C. elegans. Further, we found the decreased number of offspring, malformed somatic gonad structure, oxidative damage and autophagy induced by DEHP in parental worms can be inheritance to the not directly exposed offspring.

Sentinel supervised lung-on-a-chip: A new environmental toxicology platform for nanoplastic-induced lung injury.

Nanoplastics are prevalent in the air and can be easily inhaled, posing a threat to respiratory health. However, there have been few studies investigating the impact of nanoplastics on lung injury, especially chronic obstructive pulmonary disease (COPD). Furthermore, cell and animal models cannot deeply understand the pollutant-induced COPD. Existing lung-on-a-chip models also lack interactions among immune cells, which are crucial in monitoring complex responses. In the study, we built the lung-on-a-chip to accurately recapitulate the structural features and key functions of the alveolar-blood barrier while integrating multiple immune cells. The stability and reliability of the lung-on-a-chip model were demonstrated by toxicological application of various environmental pollutants. We Further focused on exploring the association between COPD and polystyrene nanoplastics (PS-NPs). As a result, the cell viability significantly decreased as the concentration of PS-NPs increased, while TEER levels decreased and permeability increased. Additionally, PS-NPs could induce oxidative stress and inflammatory responses at the organ level, and crossed the alveolar-blood barrier to enter the bloodstream. The expression of α1-antitrypsin (AAT) was significantly reduced, which could be served as early COPD checkpoint on the lung-chips. Overall, the lung-on-a-chip provides a new platform for investigating the pulmonary toxicity of nanoplastics, demonstrating that PS-NPs can harm the alveolar-blood barrier, cause oxidative damage and inflammation, and increase the risk of COPD.

The hepatotoxicity assessment of micro/nanoplastics: A preliminary study to apply the adverse outcome pathways.

Plastic pollution has become a significant global problem over the years, leading to the continuous decomposition and accumulation of micro/nanoplastics (MNPLs) in the environment. As a result, human exposure to these MNPLs is inevitable. The liver, in particular, is highly susceptible to potential MNPL toxicity. In this study, we systematically reviewed the current literature on MNPLs-induced hepatotoxicity and collected data on toxic events occurring at different biological levels. Then, to better understand the cause-mechanism causality, we developed an Adverse Outcome Pathway (AOP) framework for MNPLs-induced hepatotoxicity. The AOP framework provided insights into the mechanism of MNPL-induced hepatotoxicity and highlighted potential health risks such as liver dysfunction and inflammation, metabolism disorders and liver fibrosis. Moreover, we discussed the potential application of emerging toxicological models in the hepatotoxicity study. Liver organoids and liver-on-chips, which can simulate the structure and function of the liver in vitro, offer a promising alternative platform for toxicity testing and risk assessment. We proposed combining the AOP framework with these emerging toxicological models to improve our understanding of the hepatotoxic effects of MNPLs. Overall, this study performed a preliminary exploration of novel toxicological methodologies to assess the hepatotoxicity of MNPLs, providing a deeper understanding of environmental toxicology.

Upregulation of postsynaptic cAMP/PKA/CREB signaling alleviates copper(â ¡)-induced oxidative stress and pyroptosis in MN9D cells.

It has been widely reported that long-term exposure to copper increases the prevalence and mortality of Parkinson's disease. Our previous study showed that CuSO4 exposure induced a significant increase in the expression of cleaved Caspase1 proteins and the loss of dopaminergic neurons in the SNpc of mice. In this study, the effects of copper(Ⅱ) on cAMP/PKA/CREB pathway and pyroptosis-related proteins in MN9D cells were investigated by setting up copper(Ⅱ) exposure groups with different concentration gradients, to provide possible molecular evidence for studying the mechanism of copper(Ⅱ)-induced degeneration of dopaminergic neurons. We found that after 48 h of copper(Ⅱ) exposure, the cu content in MN9D cells increased in a dose-dependent manner, and the proliferation activity decreased significantly. In addition, copper(Ⅱ) exposure caused up-regulation of PDE4D and down-regulation of D1R, cAMP, PKA and p-CREB/CREB. Simultaneously, we proved that copper(Ⅱ) exposure induced oxidative stress in MN9D cells, including decreased GSH-Px content, Keap1 expression and mitochondrial membrane potential, increased malondialdehyde content, ROS intensity, and Nrf2, NQO1, HO-1, HSP-70 expression, further causing up-regulation of inflammasome and GSDMD protein. After pretreatment with Roflupram, the level of copper(Ⅱ)-induced oxidative damage decreased, the expression of inflammasome and GSDMD proteins were down-regulated. However, the protective effects of ROF were blocked by H-89. In summary, copper(Ⅱ) treatment induced oxidative stress and inflammasome-mediated pyroptosis in MN9D cells, which may be related to copper(Ⅱ)-induced postsynaptic cAMP, PKA, and CREB signal transduction disorders.

Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease.

Excessive accumulations of reactive oxygen species (ROS) and amyloid-ß (Aß) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aß fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aß fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood-brain barrier penetration and Aß binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aß plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aß deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.

Effects of tri-n-butyl phosphate (TnBP) on neurobehavior of Caenorhabditis elegans.

As an emerging flame retardant, organic phosphate flame retardants have been extensively used worldwide. The aim of this study is to determine the effects of TnBP on neurobehavior of Caenorhabditis elegans (C. elegans) and its mechanisms. L1 larvae of wild-type nematodes (N2) were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours. Then, we observed that the body length and body width were inhibited, the head swings were increased, the pump contractions and chemical trend index were reduced, the production of reactive oxygen species (ROS) was increased, and the expression of mitochondrial oxidative stress related genes (mev-1 and gas-1) and P38 MAPK signal pathway-related genes (pmk-1, sek-1, and nsy-1) was altered. After reporter gene strains BZ555, DA1240, and EG1285 were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours, the synthesis of dopamine, glutamate, and Gamma-Amino Butyric Acid (GABA) was increased. In addition, the pmk-1 mutants (KU25) led to the sensitivity of C. elegans to TnBP in terms of head swings. The results showed that TnBP had harmful effects on the neurobehavior of C. elegans, oxidative stress might be one of the mechanisms of its neurotoxicity, and P38 MAPK signal pathway might play an important regulatory role in this process. The results revealed the potential adverse effects of TnBP on the neurobehavior of C. elegans.

Ultrafast Cancer Cells Imaging for Liquid Biopsy via Dynamic Self-Assembling Fluorescent Nanoclusters.

Lung cancer-specific clinical specimens, such as alveolar lavage fluid, are typically identified by microscopic biopsy, which has limited specificity and sensitivity and is highly susceptible to human manipulation. In this work, we present an ultrafast, specific, and accurate cancer cell imaging strategy based on dynamically self-assembling fluorescent nanoclusters. The presented imaging strategy can be used as an alternative or a complement to microscopic biopsy. First, we applied this strategy to detect lung cancer cells, and established an imaging method that can rapidly, specifically, and accurately distinguish lung cancer cells (e.g., A549, HepG2, MCF-7, Hela) from normal cells (e.g., Beas-2B, L02) in 1 min. In addition, we demonstrated that the dynamic self-assembly process that fluorescent nanoclusters formed by HAuCl4 and DNA are first generated at the cell membrane and then gradually enter the cytoplasm of lung cancer cells in 10 min. In addition, we validated that our method enables the rapid and accurate imaging of cancer cells in alveolar lavage fluid samples from lung cancer patients, whereas no signal was observed in the normal human samples. These results indicate that the dynamic self-assembling fluorescent nanoclusters-based cancer cells imaging strategy could be an effective non-invasive technique for ultrafast and accurate cancer bioimaging during liquid biopsy, thus providing a safe and promising cancer diagnostic platform for cancer therapy.

Characterization of lymphocyte subsets and intestinal short-chain fatty acids in benzene-induced immunosuppressive mice.

Exposure to benzene causes immunosuppression, but the mechanism has not been clarified. In this study, mice were subcutaneously injected with different concentrations (0, 6, 30 and 150 mg/kg) of benzene for four weeks. The lymphocytes of bone marrow (BM), spleen and peripheral blood (PB) and the level of short-chain fatty acids (SCFAs) in mouse intestine were measured. The results showed that benzene exposure led to a reduction in CD3+ and CD8+ lymphocytes in mouse BM, spleen and PB, and CD4+ lymphocytes were increased in mouse spleen but decreased in mouse BM and PB after 150 mg/kg benzene exposure. In addition, Pro-B lymphocytes were reduced in mouse BM in the 6 mg/kg group. Besides, the levels of IgA, IgG, IgM, IL-2, IL-4, IL-6, IL-17a, TNF-α and IFN-γ in mouse serum were reduced after benzene exposure. Furthermore, the levels of acetic, propionic, butyric and hexanoic acid were reduced in mouse intestine, and the AKT-mTOR signaling pathway was activated in mouse BM cells after benzene exposure. Our results demonstrate that benzene induced immunosuppression in mice, and the B lymphocytes in BM are more sensible to benzene-induced toxicity. The reduction in mouse intestinal SCFAs as well as the activation of AKT-mTOR signaling may be related to the occurrence of benzene immunosuppression. Our study provides new insight for further mechanistic research on benzene-induced immunotoxicity.