Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats

Objective(s): Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in different kinds of commercial products as a plasticizer. Previous studies have revealed that exposures to DEHP could be associated with precocious puberty in teenagers, but the exact mechanism is yet to be known. Materials and Methods: In this study, 48 prepubertal Wistar female rats were randomly apportioned into 4 groups and orally treated with 0, 250, 500, and 1000 mg/kg/d DEHP from postnatal day 21 up to 4 weeks. Subsequently, we examined the indicators related to the initiation of sexual development. Results: DEHP was able to shorten the vaginal opening time and prolong the estrous cycles of female rats. IGF-1 expression was significantly upregulated by 1000 mg/kg/d DEHP in the hypothalamus, and the hypothalamic, as well as serum levels of GH, were also upregulated by DEHP. It also caused decrements in serum levels of FSH, LH, and T and the increment in level of progesterone. Meanwhile, DEHP was able to exert its effect on the mRNA and protein expression levels of Kiss-1, GPR54, and GnRH in the hypothalamus in pubertal female rats. Conclusion: These findings are revealing that DEHP exposure more likely causes imbalances of hypothalamus functioning in pubertal female rats and thus induces precautious puberty in these animals

Unraveling Controversies Over Civic Honesty Measurement: An Extended Field Replication in China

Cohn et al. (2019) conducted a wallet drop experiment in 40 countries to measure civic honesty around the globe, which has received worldwide attention but also sparked controversies over using the email response rate as the sole metric of civic honesty. Relying on the lone measurement may overlook cultural differences in behaviors that demonstrate civic honesty. To investigate this issue, we conducted an extended replication study in China, utilizing email response and wallet recovery to assess civic honesty. We found a significantly higher level of civic honesty in China, as measured by the wallet recovery rate, than reported in the original study, while email response rates remained similar. To resolve the divergent results, we introduce a cultural dimension, individualism versus collectivism, to study civic honesty across diverse cultures. We hypothesize that cultural differences in individualism and collectivism could influence how individuals prioritize actions when handling a lost wallet, such as contacting the wallet owner or safeguarding the wallet. In reanalyzing Cohn et al.\u27s data, we found that email response rates were inversely related to collectivism indices at the country level. However, our replication study in China demonstrated that the likelihood of wallet recovery was positively correlated with collectivism indicators at the provincial level. Consequently, relying solely on email response rates to gauge civic honesty in cross-country comparisons may neglect the vital individualism versus collectivism dimension. Our study not only helps reconcile the controversy surrounding Cohn et al.\u27s influential field experiment but also furnishes a fresh cultural perspective to evaluate civic honesty

Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies

Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system

Docetaxel-Encapsulating Small-Sized Polymeric Micelles with Higher Permeability and Its Efficacy on the Orthotopic Transplantation Model of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance, and the small-sized nanocarrier loaded with platinum has been adopted to address this problem which is not suitable for loading docetaxel (DTX). In the present study, we used the poly(d,l-lactide)-b-polyethylene glycol-methoxy (mPEG-b-PDLLA) to encapsulate DTX and got a small-sized polymeric micelle (SPM); meanwhile we functionalized the SPM’s surface with TAT peptide (TAT-PM) for a higher permeability. The diameters of both SPM and TAT-PM were in the range of 15–26 nm. In vitro experiments demonstrated that TAT-PM inhibited Capan-2 Luc PDAC cells growth more efficiently and induced more apoptosis compared to SPM and Duopafei. The in vivo therapeutic efficiencies of SPM and TAT-PM compared to free DTX was investigated on the orthotopic transplantation model of Capan-2 Luc. SPM exerted better therapeutic efficiency than free DTX, however, TAT-PM didn’t outperformed SPM. Overall, these results disclosed that SPM could represent a new therapeutic approach against pancreatic cancer, but its permeability to PDAC was not the only decisive factor

Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD

Xanthoangelol (XAG), a major chalcone presents in Angelica keiskei, has been employed in research to develop functional supplements or drugs due to its various pharmacological activities. Here, we investigated the underlying mechanism of XAG-induced cell death in hepatocellular carcinoma (HCC). We found that XAG inhibited the cell viability of either HepG2 or HuH7cells, and induced pyroptotic death in HuH7 cell with concomitant activation of NOD-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway. However, in GSDMD-low HepG2 cells, Caspase-1 expression modulated the underlying XAG-induced apoptosis pathway, thereby regulating cell death. VX-765, a special inhibitor of caspase-1, attenuated XAG-induced pyroptosis and apoptosis. Additionally, mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway were suppressed by XAG. These findings suggest that XAG is a promising therapeutic agent through induction of caspase-1 mediated pyroptosis and apoptosis depend on the expression of GSDMD in HCC cells

DataSheet1_Minoxidil delivered via a stem cell membrane delivery controlled release system promotes hair growth in C57BL/6J mice.docx

Objective: Umbilical cord-derived mesenchymal stem cell membrane-loaded minoxidil (MXD) nanoparticles (STCM-MXD-NPs) were prepared to investigate their effects on hair growth in C57BL/6J mice.Methods: STCM-MXD-NPs were obtained by freeze-thawing and differential centrifugation, and their effects on hair growth were evaluated using C57BL/6J mice. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Protein expression levels of marker of proliferation Ki-67 (MKI67) and β-catenin (CTNNB) in skin tissue were detected by immunohistochemistry.Results: STCM-MXD-NPs improved MXD solubility. They released the drug slowly, increasing its transdermal properties, accumulation in the skin, and content in the hair bulb tissues with a better efficacy than that of ordinary MXD. Moreover, STCM-MXD-NPs significantly upregulated the mRNA and protein levels of VEGF and IGF-1 and promoted the protein expression of MKI67 and CTNNB in mouse skin tissues, promoting mouse hair growth.Conclusion: Stem cell membrane-loaded MXD nanoparticles with slow-release properties increased MXD accumulation in the skin by improving its transdermal properties, increasing VEGF, IGF-1, MKI67, and CTNNB expression levels and promoting hair growth in C57BL/6J mice.</p

Iron Robustly Stimulates Simultaneous Nitrification and Denitrification Under Aerobic Conditions

Simultaneous nitrification and denitrification (SND) is a promising single-reactor biological nitrogen-removal method. Activated sludge with and without iron scrap supplementation (Sludge-Fe and Sludge-C, respectively) was acclimated under aerobic condition. The total nitrogen (TN) content of Sludge-Fe substantially decreased from 25.0 ± 1.0 to 11.2 ± 0.4 mg/L, but Sludge-C did not show the TN-removal capacity. Further investigations excluded a chemical reduction of NO₃^–-N by iron and a decrease of NH₄⁺-N by microbial assimilation, and the contribution of SND was verified. Moreover, the amount of aerobic denitrifiers, such as bacteria belonging to the genera <i>Thauera</i>, <i>Thermomonas</i>, <i>Rhodobacter</i>, and <i>Hyphomicrobium</i>, was considerably enhanced, as observed through Miseq Illumina sequencing method. The activities of the key enzymes ammonia monooxygenase (AMO) and nitrite oxidoreductase (NXR), which are associated with nitrification, and periplasmic nitrate reductase (NAP) and nitrite reductase (NIR), which are related to denitrification, in Sludge-Fe were 1.23-, 1.53-, 3.60-, and 1.55-fold higher than those in Sludge-C, respectively. In Sludge-Fe, the quantity of the functional gene <i>NapA</i> encoding enzyme NAP, which is essential for aerobic denitrification, was significantly promoted. The findings indicate that SND is the primary mechanism underlying the removal of TN and that iron scrap can robustly stimulate SND under aerobic environment