Airborne Nanoplastics Exposure Inducing Irreversible Glucose Increase and Complete Hepatic Insulin Resistance.

As an emerging type of pollutant, microplastics have become a global environmental problem. Approximately, a fifth of the global burden of type 2 diabetes can be attributed to air particulate pollution. However, scientific knowledge remains limited about the effects of airborne nanoplastics (NPs) exposure on metabolic diseases. In this experiment, a whole-body exposure system was used to simulate the real atmospheric environment, and three exposure concentrations combined with the actual environmental concentration were selected to explore the effects of airborne NPs on metabolic diseases. Based on histological analyses, metabolic studies, gene expression, metabolites, and molecular signaling analyses, mice exposed to airborne NPs were observed to show a phenotype of systemic inflammation and complete insulin resistance featuring excessive drinking and eating, weight loss, elevated blood glucose, and decreased triglyceride levels. After airborne NPs exposure, mice were intolerant to glucose and tolerant to insulin. In addition, airborne NPs exposure could result in long-term irreversible hyperglycemia. Together, the research findings provide a strong basis for understanding the hazards of airborne nanopollution on metabolic disorders.

Nervous system exposure of different classes of nanoparticles: A review on potential toxicity and mechanistic studies.

Nanoparticles (NPs) are generally defined as very small particles in the size range of 1-100 nm. Due to the rapid development of modern society, many new materials have been developed. The widespread use of NPs in medical applications, the food industry and the textile industry has led to an increase in NPs in the environment and the possibility of human contact, which poses a serious threat to human health. The nervous system plays a leading role in maintaining the integrity and unity of the body and maintaining a harmonious balance with the external environment. Therefore, based on two categories of organic and inorganic NPs, this paper systematically summarizes the toxic effects and mechanisms of NPs released into the nervous system. The results showed that exposure to NPs may damage the nervous system, decrease learning and cognitive ability, and affect embryonic development. Finally, a remediation scheme for NPs entering the body via the environment is also introduced. This scheme aims to reduce the neurotoxicity caused by NPs by supplementing NPs with a combination of antioxidant and anti-inflammatory compounds. The results provide a valuable reference for future research in this field.

(±)-Polysiphenol and Other Analogues via Symmetrical Intermolecular Dimerizations: A Synthetic, Spectroscopic, Structural, and Computational Study.

We report an improved total synthesis of 4,5-dibromo-9,10-dihydrophenanthrene-2,3,6,7-tetraol, (±)-polysiphenol, via intermolecular McMurray dimerization of 5-bromovanillin and subsequent intramolecular oxidative coupling as the key steps. The synthetic route is applicable to 4,5-dichloro- and 4,5-difluoro-halologues (as well as a 4,5-dialkyl-analogue). Distinctive AA'BB' multiplets in their 1H NMR spectra for the dimethylene bridges of the dibromo and dichloro compounds reveal them to be room-temperature stable atropisomers, while for the difluoro compound they present as a singlet. X-ray crystal structure determinations of their tetramethylated synthetic precursors show atropisomeric twist angles of 48°, 46°, and 32°, respectively, with the former representing the largest yet observed in any 4,5-disubstituted-9,10-dihydrophenanthrene. DFT computational studies reveal an unprecedented two-stage atropisomeric interconversion process involving time-independent asynchronous rotations of the dimethylene bridge and the biaryl axis for halologues containing chlorine or bromine, but a more synchronous rotation for the difluoro analogue.

Metabonomics analysis of semen euphorbiae and semen Euphorbiae Pulveratum using UPLC-Q-TOF/MS.

Semen Euphorbiae (SE), the dry and mature seed of Euphorbia lathyris L., a common traditional Chinese medicine, has significant pharmacological activity. However, its toxicity limits its clinical application, and less toxic Semen Euphorbiae Pulveratum (SEP) is often used clinically. To explore the possible mechanism of SE frost-making and attenuation, this study used ultrahigh-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry to perform a comprehensive metabolomics analysis of serum and urine samples from rats treated with SE and SEP, and performed histopathological evaluation of liver, kidney and colon tissues. Meanwhile, the different metabolites were visualized through multivariate statistical analysis and the HMDB and KEGG databases were used to distinguish the differential metabolites of SE and SEP to reveal related metabolic pathways and their significance. In total, 32 potential biomarkers, 14 in serum and 18 in urine, were identified. The metabolic pathway analysis revealed that arachidonic acid metabolism, sphingolipid metabolism, tyrosine and tryptophan biosynthesis, the tricarboxylic acid cycle and seven other metabolic pathways were significantly altered. Importantly, compared with SE, SEP reduced the metabolic disorder related to endogenous components. The mechanism may be related to the regulation of lipid metabolism, intestinal flora metabolites, amino acid metabolism and energy metabolism. This study provided new insights into the possible mechanism of SE freezing and attenuation.

IPSO-LSTM hybrid model for predicting online public opinion trends in emergencies.

When emergencies are widely discussed and shared, it may lead to conflicting opinions and negative emotions among internet users. Accurately predicting sudden network public opinion events is of great importance. Therefore, this paper constructs a hybrid forecasting model to solve this problem. First, this model introduces an improved inertia weight and an adaptive variation operation to enhance the Particle Swarm Optimization (PSO) algorithm. Then, the improved PSO (IPSO) algorithm optimizes the parameters of the Long Short-Term Memory (LSTM) neural network. Finally, the IPSO-LSTM hybrid prediction model is constructed to forecast and analyze emergency public opinion dissemination trends. The experimental outcomes indicate that the IPSO-LSTM model surpasses others and has high prediction accuracy. In the four emergency predictions we select, the MAPE value of IPSO-LSTM is 74.27% better than that of BP, 33.96% better than that of LSTM, and 13.59% better than that of PSO-LSTM on average. This study aims to assist authorities in quickly identifying potential public opinion crises, developing effective strategies, and promoting sustainable and positive growth in the network environment.

Associations of polysocial risk score with incident rosacea: a prospective cohort study of government employees in China.

Background: The associations between single risk factors and incident rosacea have been reported, but the effects of social risk factors from multiple domains coupled remain less studied. Objectives: To quantify the influence of social determinants on rosacea comprehensively and investigate associations between the polysocial risk score (PsRS) with the risks of incident rosacea. Methods: This was a prospective cohort study of government employees undertaken from January 2018 to December 2021 among participants aged >20 from five cities in Hunan province of China. At baseline, information was collected by a questionnaire and participants were involved in an examination of the skin. Dermatologists with certification confirmed the diagnosis of rosacea. The skin health status of participants was reassessed every year since the enrolment of study during the follow-up period. The PsRS was determined using the nine social determinants of health from three social risk domains (namely socioeconomic status, psychosocial factors, and living environment). Incident rosacea was estimated using binary logistic regression models adjusted for possible confounding variables. Results: Among the 3,773 participants who completed at least two consecutive skin examinations, there were 2,993 participants included in the primary analyses. With 7,457 person-years of total follow-up, we detected 69 incident rosacea cases. After adjustment for major confounders, participants in the group with high social risk had significantly raised risks of incident rosacea with the adjusted odds ratio (aOR) being 2.42 (95% CI 1.06, 5.55), compared to those in low social risk group. Conclusion: Our findings suggest that a higher PsRS was associated with an elevated risk of incident rosacea in our study population.

Tumor Targeting with Apatinib-loaded Nanoparticles and Sonodynamic Combined Therapy

INTRODUCTION: This study implies the enhancement of apatinib killing effect in 4T1 tumor cells through constructing drug-loaded nanoparticles apatinib/Ce6@ZIF-8@Membranes (aCZM) to enhance tumor therapeutic targeting and reduce toxic side following sonodynamic therapy (SDT). METHODS: apatinib/Ce6@ZIF-8 (aCZ) were synthesized by in situ encapsulation, and aCZM were constructed by encapsulating the nanoparticles with extracted breast cancer 4T1 cell membranes. aCZM were characterized and tested for the stability by electron microscopy, and the membrane proteins on the nanoparticles' surface were assessed using SDS-PAGE gel electrophoresis. The cell viability of 4T1 cells following treatment with aCZM was tested using cell counting kit-8 (CCK-8). The uptake of nanoparticles was detected by laser confocal microscopy and flow cytometry, and the SDT-mediated production of reactive oxygen species (ROS) was verified by singlet oxygen sensor green (SOSG), electron spin resonance (ESR), and DCFH-DA fluorescent probes. The CCK-8 assay and flow cytometry using Calcein/PI were used to assess the antitumoral effect of aCZM nanoparticles under SDT. The biosafety of aCZM was further verified in vitro and in vivo using the hemolysis assay, routine blood test and H&E staining of vital organs in Balb/c mice. RESULTS: aCZM with an average particle size of about 210.26 nm were successfully synthesized. The results of the SDS-PAGE gel electrophoresis experiment showed that aCZM have a band similar to that of pure cell membrane proteins. The CCK-8 assay demonstrated the absence of effects on cell viability at a low concentration range, and the relative cell survival rate reached more than 95%. Laser confocal microscopy and flow cytometry analysis showed that aCZM treated group has the strongest fluorescence and the highest cellular uptake of nanoparticles. SOSG, ESR, and DCFH-DA fluorescent probes all indicated that the aCZM + SDT treated group has the highest ROS production. The CCK-8 assay also showed that when the ultrasound intensity was fixed at 0.5 W/cm2, the relative cell survival rates in the medium concentration group (10 µg/ml) (5.54 ± 1.26%) and the high concentration group (20 µg/ml) (2.14 ± 1.63%) were significantly lower than those in the low concentration group (5 µg/ml) (53.40 ± 4.25%). Moreover, there was a concentration and intensity dependence associated with the cell-killing effect. The mortality rate of the aCZM in the ultrasound group (44.95±3.03%) was significantly higher than that of the non-ultrasound (17.00±2.26%) group and aCZ + SDT group (24.85 ± 3.08%) (P<0.0001). The live and dead cells' staining (Calcein/PI) also supported this result. Finally, in vitro hemolysis test at 4 and 24 hours showed that the hemolysis rate of the highest concentration group was less than 1%. The blood routine, biochemistry, and H&E staining results of major organs in Balb/c mice undergoing nano-treatments showed no obvious functional abnormalities and tissue damage in 30 days. CONCLUSION: In this study, a multifunctional bionic drug delivery nanoparticles (aCZM) system with good biosafety and compatibility in response to acoustic dynamics was successfully constructed and characterized. This system enhanced apatinib killing effect on tumor cells and reduced toxic side effects under SDT.

Associations of adherence to Mediterranean-like diet pattern with incident rosacea: A prospective cohort study of government employees in China.

Background: Despite of growing evidence on gastrointestinal comorbidities of rosacea, there was a lack of literatures regarding the role of diet on rosacea. Objectives: To investigate the relationship between adherence to a Mediterranean-like diet pattern and the risk of incident rosacea. Methods: This was a prospective cohort study of government employees aged >20 years conducted between January 2018 and December 2021 from five cities of Hunan province of China. At baseline, participants completed a food frequency questionnaire and participated in a skin examination. Presence of rosacea was determined by certified dermatologists. Subsequent skin examinations during follow-up were performed every one-year interval since the entry of the study. The Mediterranean diet score (MDS) was generated based on seven food groups (whole grains, red meats, fish, raw vegetables, legumes, fruits and nuts). Binary logistic regression models adjusted for potential confounders were used to estimate risks for incident rosacea. Results: Of the 3,773 participants who completed at least two consecutive skin examinations, 3,496 were eligible for primary analyses. With a total follow-up of 8,668 person-years, we identified 83 incident rosacea cases. After full adjustments for covariates, the MDS was associated a decreased risk of incident rosacea (aOR: 0.84, 95% CI: 0.72, 0.99; P trend = 0.037 for 1-point increment of MDS). In subgroup analyses by body mass index (BMI), this inverse association was consistently observed in the lowest and medium tertiles of BMI (<24.5 kg/m2), but not in the highest tertile of BMI (≥24.5 kg/m2), with a significant interaction effect (P < 0.001). Conclusions: Our results suggested that adherence to a Mediterranean-like diet pattern might reduce the risk of incident rosacea among non-overweight individuals.

SARS-CoV-2 vaccination in androgen sensitive phenotypes - A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients.

Background: Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection. Purpose: We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH. Method: We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy. Result: A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019). Conclusion: Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.

Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells.

BACKGROUND: It has been reported that atractylodin has a potential antitumor effect. This study aimed to investigate the effects of atractylodin on Huh7 and Hccm hepatocellular carcinoma (HCC) cells and its molecular mechanism. METHODS: Huh7 and Hccm cells were cultured in vitro, and their viability was detected by CCK-8 assay and the half inhibitory concentration (IC50) was calculated. The cells were treated with different concentrations of atractylodin, and the migration and invasion ability of cells was detected by scratch assay and Transwell assay. The cell cycle change and apoptosis rate were detected by flow cytometry. IlluminaHiSeq4000 platform was used for transcriptome sequencing, and the results were analyzed for gene differential expression, gene function, and signal pathway enrichment. Morphological changes of cells were detected by transmission electron microscopy, reactive oxygen species (ROS) levels were detected by DCFH-DA probe, and the expressions of ferroptosis related proteins GPX4, ACSL4, FTL, and TFR1 were detected by Western blot. RESULTS: The results showed that atractylodin could inhibit the proliferation, migration, and invasion of Huh7 and Hccm cells, regulate the cell cycle, and induce cell apoptosis and G1 phase cell cycle arrest. In addition, it could significantly induce the increase of intracellular ROS levels, decrease the expression of GPX4 and FTL proteins, and up-regulate the expression of ACSL4 and TFR1 proteins. CONCLUSIONS: Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, our results suggest that atractylodin may induce ferroptosis in HCC cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins.

Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae.

BACKGROUND: Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts. METHODS: A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L1, L2, and L3 in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol. RESULTS: The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen. CONCLUSION: These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L1, L2, and L3 after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.