Unexpected Inhibitory Role of Silica Nanoparticles on Lung Cancer Development by Promoting M1 Polarization of Macrophages.

Introduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive. Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors. Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression. Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer.

N6-methyladenosine demethylase FTO regulates neuronal oxidative stress via YTHDC1-ATF3 axis in arsenic-induced cognitive dysfunction.

Excessive exposure to metals in daily life has been proposed as an environmental risk factor for neurological disorders. Oxidative stress is an inevitable stage involved in the neurotoxic effects induced by metals, nevertheless, the underlying mechanisms are still unclear. In this study, we used arsenic as a representative environmental heavy metal to induce neuronal oxidative stress and demonstrated that both in vitro and in vivo exposure to arsenic significantly increased the level of N6-methyladenosine (m6A) by down-regulating its demethylase FTO. Importantly, the results obtained from FTO transgenic mice and FTO overexpressed/knockout cells indicated that FTO likely regulated neuronal oxidative stress by modulating activating transcription factor 3 (ATF3) in a m6A-dependent manner. We also identified the specific m6A reader protein, YTHDC1, which interacted with ATF3 and thereby affecting its regulatory effects on oxidative stress. To further explore potential intervention strategies, cerebral metabolomics was conducted and we newly identified myo-inositol as a metabolite that exhibited potential in protecting against arsenic-induced oxidative stress and cognitive dysfunction. Overall, these findings provide new insights into the importance of the FTO-ATF3 signaling axis in neuronal oxidative stress from an m6A perspective, and highlight a beneficial metabolite that can counteract the oxidative stress induced by arsenic.

A case report of severe left ventricular outflow tract obstruction in a middle-aged adult with chest pain and shock.

Severe left ventricular outflow tract obstruction (LVOTO) of hypertrophic cardiomyopathy is an acutely life-threatening, must-not miss, cardiology emergency that infrequently presents to the emergency department (ED). Patients with this condition usually manifest chest pain, syncope, cardiogenic shock, and severe ischemia. LVOTO is easy misdiagnosed as acute coronary syndrome. In our patient, the ECG showed a significant ST-segment depression and a 0/0 mmHg blood pressure when the peak left ventricular outflow tract gradient was abruptly increased by provocable activities. However, the patient had normal coronaries on cardiac catheterization, and, upon being immediately treated with intravenous esmolol, his symptoms were relieved and blood pressure was normal after 30 minutes. This case highlights, not only that early and exact diagnosis of LVOTO is crucial, but also the importance of the therapeutic strategies used.

RENIN AND ANGIOTENSIN (1-7) OFFER PREDICTIVE VALUE IN PEDIATRIC SEPSIS: FINDINGS FROM PROSPECTIVE OBSERVATIONAL COHORTS.

ABSTRACT: Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) ( P < 0.0001). Meanwhile, the serum angiotensin (1-7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) ( P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) ( P = 0.0001) and lower levels of angiotensin (1-7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) ( P < 0.05). A combination of renin, angiotensin (1-7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81-0.92). Conclusion: Circulating renin and angiotensin (1-7) have predictive value in pediatric sepsis.

Association between protein-to-energy ratio and overweight/obesity in children and adolescents in the United States: a cross-sectional study based on NHANES.

Background: The dietary protein proportion may be crucial in triggering overweight and obesity among children and adolescents. Methods: Cross-sectional data from 4,336 children and adolescents who participated in the National Health and Nutrition Survey (NHANES) between 2011 and March 2020 were analyzed. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Restricted cubic splines assessed the nonlinear relationships between dietary protein intake and the prevalence of overweight and obesity. Results: Adjusted logistic regression models showed that each 1% increase in dietary protein proportion was associated with a 4% higher risk of overweight and obesity (OR = 1.04, 95% CI: 1.01-1.07). A nonlinear relationship was noted in children aged 6-11 years (P < 0.05), as demonstrated by restricted cubic spline analysis. After dividing dietary protein intake into quartiles, the highest quartile had an adjusted OR of 2.07 (95% CI: 1.35, 3.16, P = 0.001) compared to the lowest, among children aged 6-11 years. Conclusion: Dietary protein intake is positively linked to overweight and obesity in American children, irrespective of individual characteristics and total energy consumption.

Protective effects of patchouli alcohol against DSS-induced ulcerative colitis.

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.

SUMOylation modification of FTO facilitates oxidative damage response of arsenic by IGF2BP3 in an m6A-dependent manner.

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.

NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death.

Vascular endothelial cells play a critical role in maintaining the health of blood vessels, but dysfunction can lead to cardiovascular diseases. The impact of arsenite exposure on cardiovascular health is a significant concern due to its potential adverse effects. This study aims to explore how NBR1-mediated autophagy in vascular endothelial cells can protect against oxidative stress and apoptosis induced by arsenite. Initially, our observations revealed that arsenite exposure increased oxidative stress and triggered apoptotic cell death in human umbilical vein endothelial cells (HUVECs). However, treatment with the apoptosis inhibitor Z-VAD-FMK notably reduced arsenite-induced apoptosis. Additionally, arsenite activated the autophagy pathway and enhanced autophagic flux in HUVECs. Interestingly, inhibition of autophagy exacerbated arsenite-induced apoptotic cell death. Our findings also demonstrated the importance of autophagy receptor NBR1 in arsenite-induced cytotoxicity, as it facilitated the recruitment of caspase 8 to autophagosomes for degradation. The protective effect of NBR1 against arsenite-induced apoptosis was compromised when autophagy was inhibited using pharmacological inhibitors or through genetic knockdown of essential autophagy genes. Conversely, overexpression of NBR1 facilitated caspase 8 degradation and reduced apoptotic cell death in arsenite-treated HUVECs. In conclusion, our study highlights the vital role of NBR1-mediated autophagic degradation of caspase 8 in safeguarding vascular endothelial cells from arsenite-induced oxidative stress and apoptotic cell death. Targeting this pathway could offer a promising therapeutic approach to mitigate cardiovascular diseases associated with arsenite exposure.

Deferasirox exerts anti-epileptic effects by improving brain iron homeostasis via regulation of ITPRIP.

Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.

Zinc Oxide Nanoparticles Exacerbate Epileptic Seizures by Modulating the TLR4-Autophagy Axis.

Background: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy. Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK-242). Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK-242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis. Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances.

Intact lung tissue and bronchoalveolar lavage fluid are both suitable for the evaluation of murine lung microbiome in acute lung injury.

BACKGROUND: Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome. METHODS AND RESULTS: To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury. CONCLUSION: This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract.

Distinguishing thermoelectric and photoelectric modes enables intelligent real-time detection of indoor electrical safety hazards.

Due to the prevalence of electronic devices, intelligent sensors have attracted much interest for the detecting and providing alarms with respect to indoor electrical safety. Nonetheless, how to effectively identify various indoor electrical safety hazards remains a challenge. In this study, we fabricated single-walled carbon nanotube/poly(3-hexylthiophene-2,5-diyl) (SWCNT/P3HT) composites with exceptional bifunctional thermoelectric and photoelectric responses. Through synergy of the thermo-/photoelectric effects, the composites yielded greatly enhanced output voltages compared with the use of thermoelectric effects alone. Interestingly, modes of heat transfer can be effectively distinguished using the nominal Seebeck coefficients. Based on the remarkable output voltages and deviations in the nominal Seebeck coefficients, we developed indoor intelligent sensors capable of effectively identifying and monitoring diverse indoor electrical conditions, including electrical overheating, fire, and air conditioning flow. This pioneering investigation proposes a novel avenue for designing intelligent sensors that can recognize heat transfer modes and hence effectively monitor indoor electrical safety hazards.

Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet.

This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with high-fat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.

Association between Residential Greenness and Human Microbiota: Evidence from Multiple Countries.

BACKGROUND: Greenness, referring to a measurement of the density of vegetated land (e.g., gardens, parks, grasslands), has been linked with many human health outcomes. However, the evidence on greenness exposure and human microbiota remains limited, inconclusive, drawn from specific regions, and based on only modest sample size. OBJECTIVES: We aimed to study the association between greenness exposure and human microbial diversity and composition in a large sample across 34 countries and regions. METHODS: We explored associations between residential greenness and human microbial alpha-diversity, composition, and genus abundance using data from 34 countries. Greenness exposure was assessed using the normalized difference vegetation index and the enhanced vegetation index mean values in the month before sampling. We used linear regression models to estimate the association between greenness and microbial alpha-diversity and tested the effect modification of age, sex, climate zone, and pet ownership of participants. Differences in microbial composition were tested by permutational multivariate analysis of variance based on Bray-Curtis distance and differential taxa were detected using the DESeq2 R package between two greenness exposure groups split by median values of greenness. RESULTS: We found that higher greenness was significantly associated with greater richness levels in the palm and gut microbiota but decreased evenness in the gut microbiota. Pet ownership and climate zone modified some associations between greenness and alpha-diversity. Palm and gut microbial composition at the genus level also varied by greenness. Higher abundances of the genera Lactobacillus and Bifidobacterium, and lower abundances of the genera Anaerotruncus and Streptococcus, were observed in people with higher greenness levels. DISCUSSION: These findings suggest that residential greenness was associated with microbial richness and composition in the human skin and gut samples, collected across different geographic contexts. Future studies may validate the observed associations and determine whether they correspond to improvements in human health. https://doi.org/10.1289/EHP12186.

Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice.

Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.

Reproductive effects of pubertal exposure to neonicotinoid thiacloprid in immature male mice.

Thiacloprid (THIA) is a kind of neonicotinoid, a widely used insecticide class. Animal studies of adult and prenatal exposure to THIA have revealed deleterious effects on mammalian sperm fertility and embryonic development. A recent cross-sectional study linked higher THIA concentrations to delayed genitalia development stages in adolescent boys, suggesting that pubertal exposure to THIA may adversely affect reproductive development in immature males. Hence, this study aimed to investigate the effects of daily oral administration of THIA during puberty on the reproductive system of developing male mice. Young male C57 BL/6 J mice aged 21 days were administrated with THIA at concentrations of 10 (THIA-10), 50 (THIA-50) and 100 mg/kg (THIA-100) for 4 weeks by oral gavage. It is found that exposure to 100 mg/kg THIA diminished sexual behavior in immature male mice, caused a decrease in the spermatogenic cell layers and irregular arrangement of the seminiferous epithelium, and down-regulated the mRNA levels of spermatogenesis-related genes Ddx4, Scp3, Atg5, Crem, and Ki67, leading to an increase of sperm abnormality rate. In addition, THIA exposure at 50 and 100 mg/kg reduced the serum levels of testosterone and FSH, and decreased the expression levels of Star and Cyp11a1 related to testosterone biosynthesis. THIA exposure at 10 mg/kg did not produce any of the above significant changes. In conclusion, the high dose of THIA exposure impaired reproductive function in immature mice. It seems that THIA has no detrimental effects on the reproductive system of mice at low dose of 10 mg/kg.

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles.

Purpose: The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin. Methods: In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase (Aanat), melatonin receptor1A (Mt1/Mtnr1a), melatonin receptor1B (Mt2/Mtnr1b), and neuropeptide Y (Npy) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed. Results: The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat, the membrane receptors Mt1 and Mt2 and Npy during the day and night. Conclusion: Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity.

Risk of Environmental Chemicals on Bone Fractures Is Independent of Low Bone Mass in US Adults: Insights from 2017 to 2018 NHANES.

To assess the association of environmental chemical factors with osteopenia and/or bone fractures. All data were extracted from the National Health and Nutrition Survey (NHANES) 2017-2018 of American adults aged 20-59 years old; invalid data were excluded based on dual-energy X-ray absorptiometry. For the ultimate valid data set, multivariate logistic regression models were applied to evaluate the association of environmental chemical factors with osteopenia and bone fractures. The valid dataset was obtained from 2640 individuals, who completed a questionnaire of demographic characteristics. Urinary manganese and monomethylarsonic acid were positively associated with osteopenia in American adults, but not bone fracture. However, several environmental factors (e.g., arsenous acid, arsenocholine, dimethylarsinic acid, and 2-thioxothiazolidine-4-carboxylic acid) did not affect bone mineral density, but were significantly associated with bone fracture. Multiple environmental chemical factors significantly affect bone mass or fracture risk. However, the risk of environmental chemical factors on fractures is independent of osteopenia in US Adults. The influence of environmental chemical factors on bone quality should be considered and monitored.

Involvement of gut-brain communication in arsenite-induced neurobehavioral impairments in adult male mice.

Arsenite is a well-documented neurotoxic metalloid that widely distributes in the natural environment. However, it remains largely unclear how arsenite affects neurological function. Therefore, in this study, the healthy adult male mice were exposed to 0.5 mg/L and 5 mg/L arsenite through drinking water for 30 and 90 days, respectively. Our results showed that there was no significant alteration in the intestine and brain for 30 days exposure, but exposure to arsenite for 90 days significantly induced a reduction of locomotor activity and anxiety-like behavior, caused pathological damage and inflammatory responses in the brain and intestine. We also found that arsenite remarkably disrupted intestinal barrier integrity, decreased the levels of lysozyme and digestive enzymes. Intriguingly, chronic exposure to arsenite significantly changed the levels of gut-brain peptides. Taken together, this study provides meaningful insights that gut-brain communication may involve in the neurobehavioral impairments of arsenite.

Disruption of the lung-gut-brain axis is responsible for cortex damage induced by pulmonary exposure to zinc oxide nanoparticles.

Increasing evidence shows that gut microbiota is important for host health in response to metal nanomaterials exposure. However, the effect of gut microbiota on the cortex damage caused by pulmonary exposure to zinc oxide nanoparticles (ZnONPs) remains mainly unknown. In this study, a total of 48 adult C57BL/6J mice were intratracheally instilled with 0.6 mg/kg ZnONPs in the presence or absence of antibiotics (ABX) treatment. Besides, 24 mice were treated with or without fecal microbiota transplantation (FMT) after the intraperitoneal administration of ABX. Our results demonstrated for the first time that dysbiosis induced by ABX treatment significantly aggravated cortex damage induced by pulmonary exposure to ZnONPs. Such damage might highly occur through the induction of oxidative stress, manifested by the enhancement of antioxidative enzymes and products of lipid peroxidation. However, ferroptosis was not involved in this process. Interestingly, our data revealed that ABX treatment exacerbated the alterations of gut-brain peptides (including Sst, Sstr2, and Htr4) induced by ZnONPs in both gut and cortex tissues. Moreover, fecal microbiota transplantation (FMT) was able to alleviate cerebral cortex damage, oxidative stress, and alterations of gut-brain peptides induced by pulmonary exposure to ZnONPs. The results together indicate that pulmonary exposure to ZnONPs causes cerebral cortex damage possibly via the disruption of the lung-gut-brain axis. These findings not only propose valuable insights into the mechanism of ZnONPs neurotoxicity but also provide a potential therapeutic method against brain disorders induced by pulmonary exposure to ZnONPs. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the The corresponding author on reasonable request.