Flavonoids: Potential therapeutic agents for cardiovascular disease.

Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They are related to plant growth and development, pigment formation, and protection against environmental stress. Flavonoids function as antioxidants and exert anti-inflammatory effects in the cardiovascular system by modulating classical inflammatory response pathways, such as the TLR4-NF-ĸB, PI3K-AKT, and Nrf2/HO-1 signalling pathways. There is increasing evidence for the therapeutic effects of flavonoids on hypertension, atherosclerosis, and other diseases. The potential clinical value of flavonoids for diseases of the cardiovascular system has been widely explored. For example, studies have evaluated the roles of flavonoids in the regulation of blood pressure via endothelium-dependent and non-endothelium-dependent pathways and in the regulation of myocardial systolic and diastolic functions by influencing calcium homeostasis and smooth muscle-related protein expression. Flavonoids also have hypoglycaemic, hypolipidemic, anti-platelet, autophagy, and antibacterial effects. In this paper, the role and mechanism of flavonoids in cardiovascular diseases were reviewed in order to provide reference for the clinical application of flavonoids in the future.

Abnormalities in Electroencephalographic Microstates in Patients with Late-Life Depression.

Background: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear. Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed. Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items. Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.

Haloketones: A class of unregulated priority DBPs with high contribution to drinking water cytotoxicity.

Although unregulated aliphatic disinfection byproducts (DBPs) had a much higher concentration and cytotoxicity than known aromatic DBPs, a recent study indicated that seven classes of regulated and unregulated priority DBPs (one and two-carbon-atom DBPs) just accounted for 16.2% of disinfected water cytotoxicity in the U.S., meaning some of the highly toxic aliphatic DBPs may be overlooked. Haloketones (HKs) are an essential class of priority DBPs with a 1-100 µg/L concentration in drinking water but lack cytotoxicity data. This study investigated the cytotoxicity of seven HKs using Chinese hamster ovary (CHO) cells. The order for cytotoxicity of HKs from most to least toxic was: 1,3-dichloroacetone (LC50: 1.0 ± 0.20 µM) ≈ 1,3-dibromoacetone (1.5 ± 0.19 µM) ≈ bromoacetone (1.9 ± 0.49 µM) > chloroacetone (4.3 ± 0.22 µM) > 1,1,3-trichloropropanone (6.6 ± 0.46 µM) > 1,1,1-trichloroacetone (222 ± 7.7 µM) > hexachloroacetone (3269 ± 344 µM). The cytotoxicity of HKs was higher than most regulated and priority aliphatic DBPs in mono-halogenated, di-halogenated, and tri-halogenated categories. A prediction model of HK cytotoxicity was developed based on the quantitative structure-activity relationship (QSAR), optimizing structures and computing descriptors with Gaussian 09 W. The average concentrations of HKs in representative drinking water samples from South Carolina (U.S.) and Suzhou (China) were 12.4 and 0.9 µg/L, respectively, accounting for 18.8% and 1.7% of their specific total DBPs measured (i.e. not TOX). For South Carolina drinking water, their contributions to total calculated additive cytotoxicity of aliphatic DBPs and overall drinking water cytotoxicity were 86.7% and 14.0%, respectively, demonstrating that HKs are an essential class of overlooked DBPs with a high contribution to drinking water cytotoxicity. Our study can help to explain the conflict that why regulated and priority DBPs (except HKs) just accounted for 16% of chlorinated drinking water cytotoxicity even enough they had much higher concentration and cytotoxicity than known aromatic DBPs.

An optimal method for diagnosing heart disease using combination of grasshopper evalutionary algorithm and support vector machines.

Due to the importance of accurate diagnosis and prompt treatment of this condition, the medical world is searching for a solution for its early detection and efficient treatment. Heart disease is one of the leading causes of death in modern society. With the development of computer science today, this issue can be resolved using computers. Data mining is one of the solutions for diagnosing this illness. One of the cutting-edge disciplines, data mining, can aid in better decision-making in many areas of medicine, including disease diagnosis and treatment. In order to improve diagnosis accuracy, a combination method using the evolutionary algorithms locust and support vector machine has been tested in this study. Use should be made of heart disease. Because of the hybrid nature of this approach, normalization is actually carried out in three steps: first, by using pre-processing operations to remove unknown and outlier data from the data set; second, by using the locust evolutionary algorithm to choose the best features from the available features; and third, by classifying the data set using a support vector machine. The accuracy criterion for the proposed method compared to Niobizin methods, neural networks, and J48 trees improved by 18 %, 30 %, and 24 %, respectively, after implementing it on the data set and comparing it with other algorithms used in the field of heart disease diagnosis.

The ideal model for determination the formation potential of priority DBPs during chlorination of free amino acids.

Amino acids (AAs) account for about 15-35% of dissolved organic nitrogen (DON), and are known as the important precursors of nitrogenous disinfection by-products (N-DBPs). Determining the formation potential (FP) of AAs to DBPs is used to reveal the key precursors of DBPs for further control, while the ideal method for N-DBPs FP of AAs during chlorination is not revealed. In this study, the ideal FP test models for five classes of priority DBPs during chlorination of four representative AAs (accounted for about 35% of total AAs) were analyzed. For haloaldehydes (HALs), haloketones (HKs), haloacetonitriles (HANs), haloacetamides (HAMs), and halonitromethanes (HNMs), their FPs during chlorination of four AAs were 0.1-13.0, 0.01-1.1, 0.1-104, not detectable (nd)-173, and nd-0.4 µg/mg, respectively. The FPs of priority DBPs had significant deviations between different FP test models and different tested AAs. For HALs, the model, whose chlorine dosage was determined by 15 × molar concentration of AAs [Cl (mM) = 15 × M](named: model II), was the ideal model. For HKs, model II was also the ideal FP test model for AAs with ≤3 carbons, while for AAs with 4 carbons, the model, whose chlorine dosage was determined by keeping the residual chlorine at 1 ± 0.2 mg/L after 24 h of reaction (named: model 4), was the ideal model. For HANs and HNMs, model 4 was the ideal FP test model for most of the studied AAs. The performance of HAMs during chlorination of amino acids was totally different from other P-DBPs, and model 3 was recommended to be the ideal model, in which chlorine dosage was determined by 3 × mass concentration of AAs [Cl (mg/L) = X × DOC]. This study is a reference that helps researchers select an ideal model for N-DBPs FP study of AAs.

Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults.

BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

Insights into the inhibition of protospacer integration via direct interaction between Cas2 and AcrVA5.

Spacer acquisition step in CRISPR-Cas system involves the recognition and subsequent integration of protospacer by the Cas1-Cas2 complex in CRISPR-Cas systems. Here we report an anti-CRISPR protein, AcrVA5, and reveal the mechanisms by which it strongly inhibits protospacer integration. Our biochemical data shows that the integration by Cas1-Cas2 was abrogated in the presence of AcrVA5. AcrVA5 exhibits low binding affinity towards Cas2 and acetylates Cas2 at Lys55 on the binding interface of the Cas2 and AcrVA5 N-terminal peptide complex to inhibit the Cas2-mediated endonuclease activity. Moreover, a detailed structural comparison between our crystal structure and homolog structure shows that binding of AcrVA5 to Cas2 causes steric hindrance to the neighboring protospacer resulting in the partial disassembly of the Cas1-Cas2 and protospacer complex, as demonstrated by electrophoretic mobility shift assay. Our study focuses on this mechanism of spacer acquisition inhibition and provides insights into the biology of CRISPR-Cas systems.

Compound heterozygous mutation of the SNX14 gene causes autosomal recessive spinocerebellar ataxia 20.

Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays. Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14. Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression. Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children's families.

Searching for Two-Neutrino and Neutrinoless Double Beta Decay of

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νßß) search. In addition, the two-neutrino case (2νßß) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νßß and 0νßß of ^{134}Xe half-lives, with limits of 2.8×10^{22} yr and 3.0×10^{23} yr at 90% confidence level, respectively. The 2νßß (0νßß) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

Insights into adsorbable organic halogen analysis: Two overlooked factors impacting water quality assessment.

Adsorbable organic halogen (AOX) represents the total amount of halogenated organics that can be adsorbed on activated carbon (AC) from samples. Measuring AOX is crucial for assessing water quality, and any erroneous estimation of AOX risks misleading decision-makers. This study demonstrated two overlooked factors that may introduce biases to AOX measurement. The first one relates to impurities in the gas transfer tubes of AOX combustion system and in the pressurized gas of AOX separation system, which resulted in significant fluctuations and high blank values (8.5-118.0 µg-Cl/L). The solutions of above issues are to warming up the combustor for several runs and replacing the pressurized air with argon gas in the separator, which could drop the blank AOX values to 9.1-10.0 µg-Cl/L. The second one involves coexisting chloride ion (Cl-) during AOX analysis, which interfered with AOX measurements (T. test, p < 0.05) even at low concentration levels (e.g., 10 mg/L Cl- in samples with 100 µg-Cl/L p-chlorophenol). Results show that AC captured 0.02-0.11 % of Cl-, resulting in 17.7-24.5 µg-Cl/L AOX responses in control samples containing 15-130 mg/L Cl- only. Furthermore, a significant mass imbalance of Cl- (3.58-8.39 %) during analysis process suggests a potential impact of residual Cl- on subsequent samples. By comparing synthetic and actual waters, samples with low dissolved organic carbon (DOC) were more susceptible to interference from Cl- on AOX measurement than those with high DOC. These findings underscore the pressing need to optimize existing AOX methods or develop alternative analytical methods to ensure accurate water quality assessment.

Percutaneous cement-augmented short-segment pedicle screw fixation plus percutaneous vertebroplasty for stage III Kummell's disease without neurological symptoms: A case report.

INTRODUCTION: The incidence of stage III Kummell's disease without neurological symptoms is increasing in elderly patients with osteoporotic thoracolumbar fractures. However, the surgical method is still controversial in this condition. This report presented a case of Kummell's disease in which percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty was performed, providing a reference for the surgical approach. CASE PRESENTATION: The patient was a 72-year-old female who presented unexplained lower back pain accompanied with limited mobility for the past three months. Based on her medical history, physical examinations, and imaging studies, it was confirmed that she had Kummell's disease in stage III without neurological symptoms. We treated her with percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty on the symptomatic vertebrae. CLINICAL DISCUSSION: The majority of patients with stage III Kummell's disease have severe osteoporosis, which result in failure of the internal fixation and a series of other complications. Maintaining the stability of the internal fixation system is crucial, especially after screwing and subsequent locking. When augmented with bone cement, the grip and pull-out resistance of the percutaneous pedicle screws enhance greatly. Simultaneously, percutaneous vertebroplasty on the symptomatic vertebrae can immediately support the spine unit's stability mechanically and maintain the shape of the vertebrae after reduction. CONCLUSIONS: The percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty on the symptomatic vertebrae is an effective treatment for stage III Kummell's disease without neurological symptoms. It can effectively restore the vertebral height, correct the kyphotic deformities, improve spinal canal stenosis, and achieve satisfactory short-term clinical outcomes.

Engineering a hollow bowl-like porous carbon-confined Ru-MgO hetero-structured nanopair as a high-performance catalyst for ammonia borane hydrolysis.

Exploration of high-performance catalysts holds great importance for on-demand H2 production from ammonia borane (AB) hydrolysis. In this work, a hollow bowl-like porous carbon-anchored Ru-MgO hetero-structured nano-pair with high-intensity interfaces is made, using a tailored design approach. Consequently, the optimized catalyst shows AB hydrolysis activity with a turnover frequency value of 784 min-1 in aqueous media and 1971 min-1 in alkaline solvent. Robust durability is also achieved, with slight deactivation after a ten-cycle test. Combined experimental and theoretical calculations validate the positive function of the interface between Ru and MgO for facilitating H transfer and boosting water activation, thus leading to improved AB hydrolysis performance. This study could be valuable in guiding the upgradation of Ru catalytic systems, to advance their practical applications.

VDRA downregulate ß-catenin/Smad3 and DNA damage and repair associated with improved prognosis in ccRCC patients.

The clear cell renal cell carcinoma (ccRCC) spotlighted the poorest survival, while chromophobe renal cell carcinoma (chRCC) was associated with the best survival. Earlier studies corroborated vitamin D receptor (VDR) was a promising molecular for improving the prognosis of RCC. In contrast to VDRA, the one of VDR isoforms, VDRB1 (VDR isoform B1) has an N-terminal extension of 50 amino acids and is less ligand-dependent. However, the functional differences between VDRA and VDRB1, and their roles in the prognosis of ccRCC and chRCC, have not been investigated. In the present study, we uncovered that the transcripts related to vitamin D pathway and cellular calcium signaling were effectively decreased in the context of ccRCC, yet failed to exert a comparable effect within chRCC. Specially, minimally levels of VDRA wherein kidneys of patients suffering from ccRCC predict shorter survival time. In addition, the protein expressions for ß-catenin/Smad3 pathway and DNA damage and repair pathways were obviously impeded in VDRA-overexpressed ccRCC cells, yet this inhibitory effect was conspicuously absent in enable VDRB1 cells. Our results provide a new idea to improve the prognosis of ccRCC via VDRA upregulation.

Reproductive toxicity of PFOA, PFOS and their substitutes: A review based on epidemiological and toxicological evidence.

Per- and polyfluoroalkyl substances (PFAS) have already drawn a lot of attention for their accumulation and reproductive toxicity in organisms. Perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), two representative PFAS, are toxic to humans and animals. Due to their widespread use in environmental media with multiple toxicities, PFOA and PFOS have been banned in numerous countries, and many substitutes have been produced to meet market requirements. Unfortunately, most alternatives to PFOA and PFOS have proven to be cumulative and highly toxic. Of the reported multiple organ toxicities, reproductive toxicity deserves special attention. It has been confirmed through epidemiological studies that PFOS and PFOA are not only associated with reduced testosterone levels in humans, but also with an association with damage to the integrity of the blood testicular barrier. In addition, for women, PFOA and PFOS are correlated with abnormal sex hormone levels, and increase the risk of infertility and abnormal menstrual cycle. Nevertheless, there is controversial evidence on the epidemiological relationship that exists between PFOA and PFOS as well as sperm quality and reproductive hormones, while the evidence from animal studies is relatively consistent. Based on the published papers, the potential toxicity mechanisms for PFOA, PFOS and their substitutes were reviewed. For males, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Apoptosis and autophagy in spermatogenic cells; (2) Apoptosis and differentiation disorders of Leydig cells; (3) Oxidative stress in sperm and disturbance of Ca2+ channels in sperm membrane; (4) Degradation of delicate intercellular junctions between Sertoli cells; (5) Activation of brain nuclei and shift of hypothalamic metabolome. For females, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Damage to oocytes through oxidative stress; (2) Inhibition of corpus luteum function; (3) Inhibition of steroid hormone synthesis; (4) Damage to follicles by affecting gap junction intercellular communication (GJIC); (5) Inhibition of placental function. Besides, PFAS substitutes show similar reproductive toxicity with PFOA and PFOS, and are even more toxic to the placenta. Finally, based on the existing knowledge, future developments and direction of efforts in this field are suggested.

GenX caused liver injury and potential hepatocellular carcinoma of mice via drinking water even at environmental concentration.

Hexafluoropropylene oxide dimer acid (GenX) is an alternative to perfluorooctanoic acid (PFOA), whose environmental concentration is close to its maximum allowable value established by the US Environmental Protection Agency, so its effects on human health are of great concern. The liver is one of the most crucial target organ for GenX, but whether GenX exposure induces liver cancer still unclear. In this research project, male C57 mice were disposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and higher concentrations (1 and 100 mg/L) for 14 weeks to explore its effects on liver injury and potential carcinogenicity in mice. GenX was found to cause a dose-dependent increase in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG). As the content of GenX in drinking water increased, so did the concentrations of Glypican-3 (GPC-3) and detachment gamma-carboxyprothrombin (DCP), indicators of early hepatocellular cancer. GenX destroyed the boundaries and arrangements of hepatocytes, in which monocyte infiltration, balloon-like transformation, and obvious lipid vacuoles were observed between cells. Following exposure to GenX, Masson sections revealed a significant quantity of collagen deposition in the liver. Alpha-feto protein (AFP), vascular endothelial growth factor (VEGF), Ki67, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene expression increased in a dose-dependent manner in the treatment group relative to the control group. In general, drinking water GenX exposure induced liver function impairment, elevated blood lipid level, caused liver pathological structure damage and liver fibrosis lesions, changed the liver inflammatory microenvironment, and increased the concentration of liver-related tumor indicator even in the environmental concentration, suggesting GenX is a potential carcinogen.

Altered resting-state brain oscillation and the associated cognitive impairments in late-life depression with different depressive severity: An EEG power spectrum and functional connectivity study.

OBJECTIVE: Cognitive impairments are prevalent in late-life depression (LLD). However, it remains unclear whether there are concurrent brain oscillation alterations in resting condition across varying level of depression severity. This cross-sectional study aims to investigate the characteristics of altered resting-state oscillations, including power spectrum and functional connectivity, and their association with the cognitive impairments in LLD with different depression severity. METHODS: A total of 65 patients with LLD and 40 elder participants without depression were recruited. Global cognition and subtle cognitive domains were evaluated. A five-minute resting-state electroencephalography (EEG) was conducted under eyes-closed conditions. Measurements included the ln-transformed absolute power for power spectrum analysis and the weighted phase lag index (wPLI) for functional connectivity analysis. RESULTS: Attentional and executive dysfunction were exhibited in Moderate-Severe LLD group. Enhanced posterior upper gamma power was observed in both LLD groups. Additionally, enhanced parietal and fronto-parietal/occipital theta connectivity were observed in Moderate-Severe LLD group, which were associated with the attentional impairment. LIMITATIONS: Limitations include a small sample size, concomitant medication use, and a relatively higher proportion of females. CONCLUSIONS: Current study observed aberrant brain activity patterns in LLD across different levels of depression severity, which were linked to cognitive impairments. The altered posterior brain oscillations may be trait marker of LLD. Moreover, cognitive impairments and associated connectivity alterations were exhibited in moderate-severe group, which may be a state-like marker of moderate-to severe LLD. The study deepens understanding of cognitive impairments with the associated oscillation changes, carrying implications for neuromodulation targets in LLD.

A global review on the abundance and threats of microplastics in soils to terrestrial ecosystem and human health.

Soil is the source and sink of microplastics (MPs), which is more polluted than water and air. In this paper, the pollution levels of MPs in the agriculture, roadside, urban and landfill soils were reviewed, and the influence of MPs on soil ecosystem, including soil properties, microorganisms, animals and plants, was discussed. According to the results of in vivo and in vitro experiments, the possible risks of MPs to soil ecosystem and human health were predicted. Finally, in light of the current status of MPs research, several prospects are provided for future research directions to better evaluate the ecological risk and human health risk of MPs. MPs concentrations in global agricultural soils, roadside soils, urban soils and landfill soils had a great variance in different studies and locations. The participation of MPs has an impact on all aspects of terrestrial ecosystems. For soil properties, pH value, bulk density, pore space and evapotranspiration can be changed by MPs. For microorganisms, MPs can alter the diversity and abundance of microbiome, and different MPs have different effects on bacteria and fungi differently. For plants, MPs may interfere with their biochemical and physiological conditions and produce a wide range of toxic effects, such as inhibiting plant growth, delaying or reducing seed germination, reducing biological and fruit yield, and interfering with photosynthesis. For soil animals, MPs can affect their mobility, growth rate and reproductive capacity. At present epidemiological evidences regarding MPs exposure and negative human health effects are unavailable, but in vitro and in vivo data suggest that they pose various threats to human health, including respiratory system, digestive system, urinary system, endocrine system, nervous system, and circulation system. In conclusion, the existence and danger of MPs cannot be ignored and requires a global effort.

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways.

Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 µM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1ß, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

Restoration of a dental defect in a patient with ectodermal dysplasia: a case report and literature review / 口腔疾病防治

Objective@#To explore the treatment options for congenitally missing teeth in patients with ectodermal dysplasia and provide a clinical reference.@*Methods@#A patient with ectodermal dysplasia with a concave midface, anterior protrusion of the chin, and underdevelopment of the lower third of the face presented with congenital loss of multiple maxillary teeth, malocclusion of the remaining teeth, congenital loss of mandibular dentition, small dental arches, and upper and lower alveolar bone hypoplasia. The patient was treated by means of a removable partial maxillary prosthesis, implants in the anterior region of the lower mandible designed with the assistance of digital guides, and bar-clamped implant-overlay prostheses. A literature review of the protocol for the treatment of this condition was also conducted.@*Results@#In addition to good retention and stability after denture wear, an excellent occlusal relationship, improvement of the patient's facial appearance, including upper and lower lip fullness, more equal balancing of the lower and middle 1/3 of the face, and improved masticatory function were achieved. The results of the literature review showed that patients with ectodermal dysplasia who are congenitally edentulous usually have a complex intraoral situation that makes restoration difficult, and common restorative modalities for these patients include fixed bridges, removable partial dentures, complete dentures, overdentures, and implant prostheses, which need to be selected according to the actual intraoral situation of each patient. Currently, there is no consensus on the treatment of congenitally missing teeth in patients with ectodermal dysplasia, and some scholars have suggested that fixed restorations be recommended for patients with fewer missing teeth, while the option of removable or implant-covered denture restorations should be given to patients with more missing teeth, with removeable prostheses for underage patients that are replaced with permanent fixed prostheses when the jaws have stabilized.@*Conclusion@#In patients with ectodermal dysplasia with congenital tooth loss, all factors should be taken into account, and an individualized restorative plan should be developed.