Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption.

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Modeling and characterization of gas coupled ultrasonic transducers at low pressures and temperatures and implications for sonic anemometry on Mars.

A sonic anemometer targeted at wind speed measurements on the surface of Mars is described. This environment requires transducer operation in 4-10 mbar CO2 at temperatures between 143 and 293 K (-130 °C and 20 °C, respectively). Over these ranges, transducer pressure and temperature sensitivity could be a source of measurement error. To investigate this, four candidate transducers were tested using transmission mode ultrasonic testing and impedance measurements: two narrowband piezoelectric transducers, a broadband capacitive transducer, and a micromachined capacitive ultrasound transducer. A system model was used for comparison and interpretation, and implications for a sonic anemometer were examined. Variation of transducer characteristics, including diffraction effects, across 2-10 mbar in CO2 and 190-293 K (-83 °C-20 °C) result in ±2.3% error in wind speed measurement and ±1.1% error in speed of sound measurement for the worst case but only ±0.14% error in wind and ±0.07% error in speed of sound for the best transducer operated off resonance. The acoustic conditions on Mars are similar to those in Earth's stratosphere at 30-42 km of altitude. Hence, testing was also conducted in dry air over the same range of pressures and temperatures with relevance to a secondary application of the instrument as a stratospheric anemometer for high altitude balloon missions on Earth.

Skin Electrodes Based on TPU Fiber Scaffolds with Conductive Nanocomposites with Stretchability, Breathability, and Washability.

In the context of an aging population and escalating work pressures, cardiovascular diseases pose increasing health risks. Electrocardiogram (ECG) monitoring presents a preventive tool, but conventional devices often compromise comfort. This study proposes an approach using Ag NW/TPU composites for flexible and breathable epidermal electronics. In this new structure, TPU fibers are used to support Ag NWs/TPU nanocomposites. The TPU fiber-reinforced Ag NW/TPU (TFRAT) nanocomposites exhibit excellent conductivity, stretchability, and electromechanical durability. The composite ensures high steam permeability, maintaining stable electrical performance after washing cycles. Employing this technology, a flexible ECG detection system is developed, augmented with a convolutional neural network (CNN) for automated signal analysis. The experimental results demonstrate the system's reliability in capturing physiological signals. Additionally, a CNN model trained on ECG data achieves over 99% accuracy in diagnosing arrhythmias. This study presents TFRAT as a promising solution for wearable electronics, offering both comfort and functionality in long-term epidermal applications, with implications for healthcare and beyond.

Tris-Functionalized Polyoxotungstovanadate-Mediated Antitumor Efficacy Involves Multiple Cell Death Pathways.

Polyoxometalates (POMs) are promising inorganic drug candidates for cancer chemotherapy. They are becoming attractive because of their easy accessibility and low cost. Herein, we report the synthesis and antitumor activity studies of four Lindqvist-type POMs with mixed-addenda atoms Na2[V4W2O16{(OCH2)3CR}] (R=-CH2OH, -CH3, -CH2CH3) and (Bu4N)2[V3W3{(OCH2)3CH2OOCCH2CH3}]. Compared with the current clinical applied antitumor drug 5-fluorouracil (5-FU) or Gemcitabine, analysis of MTT/CCK-8 assay, colony formation and wound healing assay revealed that the {V4W2} POMs had acceptable cytotoxicity in normal cells (293T) and significant inhibitory effects on cell proliferation and migration in three human tumor cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa), and human breast cancer cells (MCF-7). Interestingly, among the POMs analyzed, the therapeutic index (TI) of the {V4W2} POM with R= -CH2OH was relatively the most satisfactory. Thus, it was subsequently used for further studies. Flow cytometry analysis showed it prompted cellular apoptosis rate. qRT-PCR and Western blotting analysis indicated that multiple cell death pathways were activated including apoptosis, autophagy, necroptosis and pyroptosis during the POM-mediated antitumor process. In conclusion, our study shows that the polyoxotungstovanadate has great potential to be developed into a broad-spectrum antitumor chemotherapeutic drug.

Exposure risk and emergency evacuation modeling of toxic gas leakage in urban areas under the influence of multiple meteorological factors.

Frequent toxic gas leakage accidents in urban environments cannot be timely controlled and often cause great harm due to the many factors affecting gas diffusion. In this study, based on the coupling method of the Weather Research and Forecasting Model (WRF) and the open source OpenFOAM software platform, the chlorine gas diffusion process at different temperatures, wind speeds, and wind directions in a chemical laboratory and nearby urban areas in Beijing was studied numerically. A dose-response model was used to calculate chlorine lethality and assess exposure risk at the pedestrian level. To predict the evacuation path, an improved ant colony algorithm, a greedy heuristic search algorithm based on the dose-response model, was applied. The results demonstrated that the combination of WRF and OpenFOAM could consider the effects of various factors such as temperature, wind speed, and wind direction on the diffusion of toxic gases. The direction of chlorine gas diffusion was affected by wind direction, and the range of chlorine gas diffusion was affected by temperature and wind speed. The area of high exposure risk (fatality rate above 40%) at high temperatures was 21.05% larger than that at low temperatures. When the wind direction was opposite the building, the high exposure risk area was 78.95% smaller than that under the building direction. The present work provides a promising approach for exposure risk assessment and evacuation planning for the emergency response to urban toxic gas leakage.

Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish.

As an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of TCPP exposure (5-25 mg/L) on lipid homeostasis in larval and adult zebrafish (Danio rerio). TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in obesity and excessive lipid accumulation in zebrafish liver. Mechanistically, TCPP induced the over-expression of adipogenesis genes and suppressed the expression of fatty-acid ß-oxidation genes. Consequently, excess lipid synthesis and deficient expenditure triggered oxidative damage and an inflammation response by disrupting the antioxidant system and over-expressing proinflammatory cytokine. Based on high-throughput transcriptome sequencing, we found that TCPP exposure led to enrichment of several pathways involved in lipid metabolism and inflammation, as well as several genes related to pathways of cancer. Notably, increasing expressions of Ki-67 and 53BP1 proteins, which are reliable biomarkers for recognition and risk prediction of cellular proliferation in cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic TCPP exposure triggers a potential risk of hepatocellular carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus flame retardants on humans.

Alternation of supragingival microbiome in patients with cirrhosis of different Child-Pugh scores.

OBJECTIVES: The aim of this study was to analyze the differences in the taxonomy and functions of oral microbiome between patients with and without cirrhosis. MATERIALS AND METHODS: In this study, V4-16S rDNA amplicon sequencing was used to compare the difference of supragingival microbiome in 42 patients and 12 healthy individuals. RESULTS: Overall, 3,223,529 clean reads were generated, with an average of 59,694 ± 1,548 clean reads per sample. A total of 30 phyla, 78 classes, 116 orders, 167 families, 228 genera, and 114 species were detected in the 54 samples. The differences were detected among groups at each taxonomical level. Functional prediction showed that patients with cirrhosis had a significant higher proportion of the genes associated with carbohydrate transport and metabolism, defense mechanisms, infectious diseases, membrane transport, etc. compared with healthy individuals (p < .05). CONCLUSIONS: In conclusion, significant differences were observed in compositions and predictive functions of the supragingival microbiome between patients with cirrhosis and that in healthy people. These findings will provide a new insight into the understanding of pathogenesis, diagnosis, prognosis, and therapy of cirrhosis.

Gas-Sensing Properties of the SiC Monolayer and Bilayer: A Density Functional Theory Study.

Using density functional theory calculations, the adsorption of gaseous molecules (NO, NO2, NH3, SO2, CO, HCN, O2, H2, N2, CO2, and H2O) on the graphitic SiC monolayer and bilayer has been investigated to explore the possibilities in gas sensors for NO, NO2, and NH3 detection. The strong adsorption of NO2 and SO2 on the SiC monolayer precludes its applications in nitride gas sensors. The nitride gases (NO, NO2, and NH3) are chemisorbed on the SiC bilayer with moderate adsorption energies and apparent charge transfer, while the other molecules are all physisorbed. Further, the bilayer can effectively weaken the adsorption strength of NO2 and SO2 molecules, that is, NO2 molecules are only weakly chemisorbed on the SiC bilayer with an E ads of -0.62 eV, while SO2 are physisorbed on the bilayer. These results indicate that the SiC bilayer can serve as a gas sensor to detect NO, NO2, and NH3 gases with excellent performance (high sensitivity, high selectivity, and rapid recovery time). Moreover, compared with other molecular adsorptions, the adsorption of NH3 molecules significantly changes the work function of the SiC monolayer and bilayer, indicating that they can be used as optical gas sensors for NH3 detection.

Si2BN monolayers as promising candidates for hydrogen storage.

Hydrogen storage properties of the pure Si2BN monolayer were studied using density functional theory calculations. The interaction of H2 molecules with the Si2BN monolayer is weak and of electrostatic nature. The average hydrogen adsorption energies are within the ideal range of practical applications (0.187-0.214 eV), and the consecutive adsorption energies indicate that the spontaneous adsorption of H2 molecules on the Si2BN monolayer can occur. The hydrogen gravimetric density of the periodic Si2BN monolayer reaches 8.5 wt%, which exceeds the standard of 6.0 wt% set by the US Department of Energy (DOE) by the year 2020. The estimated desorption temperatures show the desirable properties for the long term recycling of the Si2BN storage medium. Thus, our results show that the Si2BN monolayer is a promising candidate for molecular hydrogen storage.

[Comparison of flavonoids content in huangqi gnizhi wuwu tang of different dosages by uniform design method].

OBJECTIVE: To determine the content of flavonoids in huangqi guizhi wuwu tang (HQGZWWT) of different dosages by uniform design method and analyze their difference for clinical application. METHODS: The uniform design set five factors and 11 levels to explore the content of flavonoids. The results were analyzed by computer with the method of multiple regression analysis. RESULTS: The contribution of each medicinal material to the content of total flavonoids was Radix Astragali (51.8%), Rhizoma Zingiberis (0.967%), Rhizoma Zingiberis (0.689%), Ramulus Cinnamomi (0.381%) and Raidix Paenoiae alba (0.185%), respectively. CONCLUSION: The extraction rate of flavonoids is not directly relative to the total amount of medicines, instead, there is an optimum dosage matching for it.