Novel Insight into the mechanism of di (2-ethylhexyl) phthalate (DEHP) impairing early follicle development.

Di (2-ethylhexyl) phthalate (DEHP), an artificially synthetic plasticizer, is a widespread environmental endocrine disruptor, which has raised substantial concern among the public about its potential reproductive toxicity effects. Taking large amounts of DEHP disrupts the normal functioning of the ovaries, however, the toxicological effects and the mechanisms by which DEHP impairs fetal folliculogenesis remain poorly understood. Our research aims to elucidate the associations between utero exposure to DEHP and fetal folliculogenesis in offspring. In this research, we monitored the spatiotemporal and expression levels of GDF9-Hedgehog (Hh) pathway-related genes during postnatal days 3-14, confirming initially the potential associations between defects in theca cell development and the downregulation of GDF9-Hh signaling. Moreover, utilizing an ovarian organ in vitro culture model, rescue validation experiments demonstrated that the addition of recombinant GDF9 protein effectively alleviate the theca cell damage caused by DEHP, thus supporting the aforementioned associations. In conclusion, our findings validate the significant role of the GDF9-Hh pathway in the enduring reproductive toxicity resulting from prenatal exposure to DEHP.

Clinical nutrition service capacity of 445 secondary or above hospitals in Sichuan, China: the 2021 annual survey.

BACKGROUND AND OBJECTIVES: To investigate the capacity of clinical nutrition services in secondary and tertiary hospitals in the Sichuan Province, China. METHODS AND STUDY DESIGN: Convenience sampling was used. E-questionnaires were distributed to all eligible medical institutions in Sichuan through the official network of provincial and municipal clinical nutrition quality control centers. The data obtained were sorted in Microsoft Excel and analyzed by SPSS. RESULTS: A total of 519 questionnaires were returned, of which 455 were valid. Only 228 hospitals were accessible to clinical nutrition services, of which 127 hospitals had independently set up clinical nutrition departments (CNDs). The ratio of clinical nutritionists to beds was 1:214. During the last decade, the rate of constructing new CNDs was maintained at approximately 5 units/year. A total of 72.4% of hospitals managed their clinical nutrition units as part of their medical technology departments. The specialist number ratio of senior, associate, intermediate and junior is approximately 1:4:8:10. There were 5 common charges for clinical nutrition. CONCLUSIONS: The sample representation was limited, and the capacity of clinical nutrition services may have been overestimated. Secondary and tertiary hospitals in Sichuan are currently in the second high tide of department establishment, with a positive trend of departmental affiliation standardization and a basic formation of a talent echelon.

MitoQ Protects Ovarian Organoids against Oxidative Stress during Oogenesis and Folliculogenesis In Vitro.

Ovarian organoids, based on mouse female germline stem cells (FGSCs), have great value in basic research and are a vast prospect in pre-clinical drug screening due to their properties, but the competency of these in vitro-generated oocytes was generally low, especially, in vitro maturation (IVM) rate. Recently, it has been demonstrated that the 3D microenvironment triggers mitochondrial dysfunction during follicle growth in vitro. Therefore, therapies that protect mitochondria and enhance their function in oocytes warrant investigation. Here, we reported that exposure to 100 nM MitoQ promoted follicle growth and maturation in vitro, accompanied by scavenging ROS, reduced oxidative injury, and restored mitochondrial membrane potential in oocytes. Mechanistically, using mice granulosa cells (GCs) as a cellular model, it was shown that MitoQ protects GCs against H2O2-induced apoptosis by inhibiting the oxidative stress pathway. Together, these results reveal that MitoQ reduces oxidative stress in ovarian follicles via its antioxidative action, thereby protecting oocytes and granulosa cells and providing an efficient way to improve the quality of in vitro-generated oocytes.

Evidence of Formation of Monolayer Hydrated Salts in Nanopores.

Despite much effort being devoted to the study of ionic aqueous solutions at the nanoscale, our fundamental understanding of the microscopic kinetic and thermodynamic behaviors in these systems remains largely incomplete. Herein, we reported the first 10 µs molecular dynamics simulation, providing evidence of the spontaneous formation of monolayer hexagonal honeycomb hydrated salts of XCl2·6H2O (X = Ba, Sr, Ca, and Mg) from electrolyte aqueous solutions confined in an angstrom-scale slit under ambient conditions. By using both the classical molecular dynamics simulations and the first-principles Born-Oppenheimer molecular dynamics simulations, we further demonstrated that the hydrated salts were stable not only at ambient temperature but also at elevated temperatures. This phenomenon of formation of hydrated salt in water is contrary to the conventional view. The free energy calculations and dehydration analyses indicated that the spontaneous formation of hydrated salts can be attributed to the interplay between ion hydration and Coulombic attractions in the highly confined water. In addition to providing molecular-level insights into the novel behavior of ionic aqueous solutions at the nanoscale, our findings may have implications for the future exploration of potential existence of water molecules in the saline deposits on hot planets.

Site-bond percolation model of epidemic spreading with vaccination in complex networks.

To study disease transmission with vaccination based on the network, we map an SIR model to a site-bond percolation model. In the case where the vaccination probability is zero, this model degenerates into a bond percolation model without the immunization. Using the method of generation functions, we obtain exact theoretical results for the epidemic threshold and the average outbreak size. From these exact solutions, we find that the epidemic threshold increases while the average outbreak size decreases with vaccination probability. Numerical simulations show that the size of giant component S increases with transmissibility T but decreases with the probability of vaccination. In addition, we compare the epidemic threshold and the size of the giant component for a Poisson network, an exponential network and a power-law network using numerical simulations. When the probability of vaccination is fixed, the epidemic threshold is the smallest for heterogeneous networks and the size of giant component S in homogeneous networks becomes largest for large transmissibility T(T close to 1).

Mesenchymal stem cell therapies for Alzheimer's disease: preclinical studies.

Alzheimer's disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder that is characterized by memory failure, cognitive impairment, as well as behavioral and psychological manifestations. Drugs can only moderately manage, but not alleviate, clinical symptoms. Results, based on animal models, have demonstrated that cell therapy is a promising strategy for treating neurodegenerative disorders. The homing effect of mesenchymal stem cells (MSCs) replaces damaged cells, while some scholars believe that the paracrine effects play a crucial role in treating diseases. In fact, these cells have rich sources, exhibit high proliferation rates, low tumorigenicity, and immunogenicity, and have no ethical concerns. Consequently, MSCs have been used across various disease aspects, such as regulating immunity, nourishing nerves, and promoting regeneration. Deterioration of public health status have exposed both Alzheimer's patients and researchers to various difficulties during epidemics. In this review, we discuss the advances and challenges in the application of mesenchymal stem cell therapy for treatment of Alzheimer's disease.

Spatial-heterogeneous granulation of organic amendments and chemical fertilizer stimulated N2O emissions from agricultural soil: An microcosm study.

The promising application modes of organic fertilizer (OF) and chemical nitrogen (N) fertilizer (CF) could be the homogeneous granulation (HG: OF and CF are distributed spatially evenly) and spatial heterogeneous granulation (SG: OF and CF are distributed separately in space), where the N transformation processes, such as the nitrous oxide (N2O) emissions, are greatly influenced by the spatial distribution of the OF and CF, particularly. Currently, there is a lack of in-depth understanding about the microbial mechanisms of the SG and HG application on N2O emissions, and the related functional guilds (ammonia oxidizers and heterotrophic denitrifiers) respond to the granular fertilizer is yet not known. In the present study, we made CF (15N-(NH4)2SO4), cow compost and maize straw (2% or 8% based on the N proportion) into granular of 1 cm in diameter, in HG and SG forms, respectively, and then applied these granules in soils for 80 days incubation. Results showed that, compared with HG treatments, the SG treatment promoted the ammonium (NH4+), nitrate (NO3-) and microbial biomass carbon (MBC) intensities, and increased the N2O emissions possibly through ammonia oxidize bacteria dependent nitrification and fungal denitrification. In addition, the high maize residues proportion in organic fertilizer significantly mitigated N2O emissions by the coupled impacts of suppressed nitrification and enhanced denitrification enzyme activity with high C input. Overall, our results suggest that spatial heterogeneous granulation of and CF may induce higher risk of N2O emissions and the higher proportion of maize residues could potentially mitigate such increased emissions.

Exploration and implementation for the construction of the quaternary teaching system of medical genetics including teaching, practice, research and clinical application.

Medical genetics, the connection between basic and clinical medicine, is a subject with strong applicability and plays important role in modern medical education system. Based on years of teaching experience and during the construction of state-level top quality course, our teaching team has established the quaternary teaching system of medical genetics which includes teaching, practice, research and clinical application. The four elements of the system interpenetrate, complement and reinforce each other. Specifically, classroom teaching is the basics which is further complemented by social practice, improved by research and promoted by clinical application. The quaternary teaching system provides a feasible way to integrate theoretical and clinical courses. After years of implementation, the teaching system has got great effects on the obvious improvement of research ability, social reputation and clinical service capacities of the research team.

A colorimetric platform for sensitive sensing of Hg2+ and S2- based on Se-AuNPs with Hg2+-activated peroxidase-like activity.

Herein, the selenium (Se) modified gold nanoparticles (Se-AuNPs) was synthesized using cerium doped carbon dots (Ce-CDs) as a reducing agent and template. As desired, Se-AuNPs displays enhanced peroxidase (POD)-like activity in the presence of Hg2+. The mechanism for the enhanced activity was attributed to the increased affinity between Se-AuNPs-Hg2+ and the substrate, in which Se and Au elements have a strong binding capacity to Hg2+, forming Hg-Se bonds and Au-Hg amalgam to generate more ·OH. This POD-like activity of Se-AuNPs-Hg2+ correlates with the colorimetric reaction by the catalytic reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The oxidation of TMB was completely inhibited by the introduction of the reductive S2-. Based on the above findings, a strategy for the colorimetric detection of Hg2+ and S2- by Se-AuNPs was established with linear ranges of 0.33-66 µg/L and 0.625-75 µg/L, and low detection limits of 0.17 µg/L and 0.12 µg/L (3.3 δ/k), respectively. When the colorimetric probes for detection of Hg2+ and S2- was applied in environmental water samples, the recoveries were in the range of 90.3-108.0 %. This method will provide a new idea for the colorimetric detection strategy of Hg2+ due to the strong interaction between Hg and Se.

Fenton-ultrasound treatment of corn stalks enhances humification during composting by stimulating the inheritance and synthesis of polyphenolic compounds-preliminary evidence from a laboratory trial.

The impact of Fenton-ultrasound treatment on the production of polyphenols and humic acid (HA) during corn stalk composting was investigated by analyzing the potential for microbial assimilation of polysaccharides in corn stalks to generate polyphenols using a13C-glucose tracer. The results showed that Fenton-ultrasound treatment promoted the decomposition of lignocellulose and increased the HA content, degree of polymerization (DP), and humification index (HI). The primary factor could be attributed to Fenton-ultrasound treatment-induced enhanced the abundance of lignocellulose-degrading microorganisms, as Firmicutes, Actinobacteria phylum and Aspergillis genus, which serve as the primary driving forces behind polyphenol and HA formation. Additionally, the utilization of a13C isotope tracer revealed that corn stalk polysaccharide decomposition products can be assimilated by microbes and subsequently secrete polyphenolic compounds. This study highlights the potential of microbial activity to generate phenolic compounds, offering a theoretical basis for increasing polyphenol production and promoting HA formation during composting.

Investigating the Dewatering Efficiency of Sewage Sludge with Optimized Ratios of Electrolytic Manganese Residue Components.

As an industrial waste residue, Electrolytic Manganese Residue (EMR) can greatly promote sludge dewatering and further particle-size optimization can significantly strengthen sludge dewaterability. In this study, the effects of ammonium sulfate, calcium sulphate dihydrate, and manganese carbonate in EMR on sludge dewatering performance were investigated using the response surface optimization method. It was found that the optimized ratio of three components in EMR was 1.0:1.6:2.2 based on capillary suction time (CST), specific resistance of filtration (SRF), and zeta potential of dewatered sludge. The composition ratio of particle-size optimized EMR was modified based on the above optimization, resulting in a significant increase in sludge dewatering performance (CST and SRF reduced by 8.7% and 11.2%, respectively). Compared with those in original sludge, the content of bound extracellular polymeric substances in the conditioned sludge with optimized ratio was drastically reduced while that of soluble extracellular polymeric substances was slightly increased, which was in accordance with the decline of fluorescence intensity. These findings indicated the disintegration of extracellular polymeric substances, the enhancement of hydrophobicity, and dewatering properties of the sludge. In summary, optimized EMR can effectively intensify the dewaterability of sludge, providing a competitive solution for dewatering and further disposal of sludge.

Cycloleucine induces neural tube defects by reducing Pax3 expression and impairing the balance of proliferation and apoptosis in early neurulation.

S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (Pax3) gene is involved in neural tube closure. However, the exact mechanism between Pax3 and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of Pax3 on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and Pax3 were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of Pax3. These results suggest that decreased expression of Pax3 impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs.

Distinct biophysical and chemical mechanisms governing sucrose mineralization and soil organic carbon priming in biochar amended soils: evidence from 10 years of field studies.

While many studies have examined the role of biochar in carbon (C) accrual in short-term scale, few have explored the decadal scale influences of biochar on non-biochar C, e.g., native soil organic C (SOC) and added substrate. To address this knowledge gap, soils were collected from decade-old biochar field trials located in the United Kingdom (Cambisol) and China (Fluvisol), with each site having had three application rates (25-30, 50-60 and 75-100 Mg ha-1) of biochar plus an unamended Control, applied once in 2009. We assessed physicochemical and microbial properties associated with sucrose (representing the rhizodeposits) mineralization and the priming effect (PE) on native SOC. Here, we showed both soils amended with biochar at the middle application rate (50 Mg ha-1 biochar in Cambisol and 60 Mg ha-1 biochar in Fluvisol) resulted in greater substrate mineralization. The enhanced accessibility and availability of sucrose to microorganisms, particularly fast-growing bacterial genera like Arenimonas, Spingomonas, and Paenibacillus (r-strategists belonging to the Proteobacteria and Firmicutes phyla, respectively), can be attributed to the improved physicochemical properties of the soil, including pH, porosity, and pore connectivity, as revealed by synchrotron-based micro-CT. Random forest analysis also confirmed the contribution of the microbial diversity and physical properties such as porosity on sucrose mineralization. Biochar at the middle application rate, however, resulted in the lowest PE (0.3 and 0.4 mg of CO2-C g soil-1 in Cambisol and Fluvisol, respectively) after 53 days of incubation. This result might be associated with the fact that the biochar promoted large aggregates formation, which enclosed native SOC in soil macro-aggregates (2-0.25 mm). Our study revealed a diverging pattern between substrate mineralization and SOC priming linked to the biochar application rate. This suggests distinct mechanisms, biophysical and physicochemical, driving the mineralization of non-biochar carbon in a field where biochar was applied a decade before. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00327-0.

Dispose of Chinese cabbage waste via hydrothermal carbonization: hydrochar characterization and its potential as a soil amendment.

Landfill of waste biomass not only poses a threat to environmental protection but also leads to a great waste of biomass resources. Hydrothermal carbonization (HTC) has been considered a promising method to convert the wet biomass into hydrochar, a high-value-added product with multiple application potentials. The cabbage waste, typical wet waste biomass with a huge production per year, was hydrothermally carbonized under 190 °C and 260 °C, respectively. The results indicated that the majority of nutrients from feedstock were dissolved in spent liquor during HTC, with only a few amounts retained on hydrochar. Temperature showed a more significant impact on hydrochar properties than retention time, which enables hydrochar to be potentially used as a soil conditioner. Particularly, the hydrochar produced at 190 °C could improve plant nutrition in the short term, while that produced at 260 °C may benefit in C sequestration. Moreover, the hydrochar dominated by meso/macropores (> 90%) would be conducive to the storage of plant-available water. But both BTX and VOCs may release during hydrochar application; thus, further field experiments are needed to test the environmental risks of hydrochar when applied as a soil amendment.

Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro.

Ovarian organoids, based on female germline stem cells (FGSCs), are nowadays widely applied for reproductive medicine screening and exploring the potential mechanisms during mammalian oogenesis. However, there are still key issues that urgently need to be resolved in ovarian organoid technology, one of which is to establish a culture system that effectively expands FGSCs in vitro, as well as maintaining the unipotentcy of FGSCs to differentiate into oocytes. Here, FGSCs were EED226 treated and processed for examination of proliferation and differentiation in vitro. According to the results, EED226 specifically increased FGSC survival by decreasing the enrichment of H3K27me3 on Oct4 promoter and exon, as well as enhancing OCT4 expression and inhibiting P53 and P63 expression. Notably, we also found that FGSCs with EED226 treatment differentiated into more oocytes during oogenesis in vitro, and the resultant oocytes maintained a low level of P63 versus control at early stage development. These results demonstrated that inhibition of EED activity appeared to promote the survival of FGSCs and markedly inhibited their apoptosis during in vitro differentiation. As a result of our study, we propose an effective culture strategy to culture FGSCs and obtain oocytes in vitro, which provides a new vision for oogenesis in vitro.

SERS detection of Hg2+ and aflatoxin B1 through on-off strategy of oxidase-like Au@HgNPs/carbon dots.

In this work, cerium-doped carbon dots (Ce-CDs) both as a reducing agent and template hybrid gold nanoparticles (AuNPs) with weak oxidase-like (OXD) activity was synthesized for the detection of Hg2+ and aflatoxin B1 (AFB1). The AuNPs can catalyze efficiently mercury ion (Hg2+) reduction to the metallic (Hg0) to form Au-Hg amalgam (Au@HgNPs). The obtained Au@HgNPs with strong OXD-like activity oxidize without Raman-active leucomalachite green (LMG) into the Raman-active malachite green (MG) and simultaneously as the SERS substrates by the formed Raman "hot spot" through MG-induced Au@HgNPs aggregation. While AFB1 was introduced resulting in the SERS intensity decreasing due to Hg2+ with AFB1 via carbonyl group to inhibit the aggregation of Au@HgNPs. The work paves a new path for the design of a nanozyme-based SERS protocol for tracing Hg2+ and AFB1 residues in foodstuff analysis.

circPTN Promotes the Progression of Non-Small Cell Lung Cancer through Upregulation of E2F2 by Sponging miR-432-5p.

Background: Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers, accounting for around 80% of total lung cancer cases worldwide. Exploring the function and mechanism of circRNAs could provide insights into the diagnosis and treatment for NSCLC. Methods: In this study, we collected tumor tissues and adjacent normal tissues from NSCLC patients to detect the expression level of circPTN and analyzed the association of its expression level with the clinicopathological parameter of NSCLC patients. Moreover, the functional engagement of circPTN in NSCLC cells was examined by cell counting kit-8 (CCK-8) cell proliferation assay, transwell migration and invasion assays, and tube formation assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) analysis were used to detect gene and protein expression, respectively. The molecular targets of cicrPTN were predicted using starBase online resources, which was validated by RNA immunoprecipitation (RIP) and dual-luciferase reporter assay. Results: Compared with adjacent normal tissues, there was a remarkable increase of the circPTN levels in NSCLC tissues. A high level of circPTN expression was associated with more lymph node metastasis (LNM) and advanced TNM stages. Functionally, circPTN knockdown inhibited the proliferation, migration, and invasion and tube formation ability of NSCLC cells. We further demonstrated that circPTN regulated the malignant phenotype of NSCLC cells through targeting the miR-432-5p/E2F2 axis. Conclusion: Together, our results suggest that circPTN, which is upregulated in NSCLC tissues, could serve as a prognostic marker for NSCLC patients. circPTN regulates the malignant progression of NSCLC cells through targeting the miR-432-5p/E2F2 axis, which may be employed as a potential strategy for the management of NSCLC.

Continuous and First-Order Liquid-Solid Phase Transitions in Two-Dimensional Water.

Understanding the phase behaviors of nanoconfined water is of importance in fundamental physical science and nanofluidic applications. Herein, we perform sub-microsecond to microsecond long molecular-dynamics (MD) simulations to show evidence of continuous and first-order phase transitions of water confined between two smooth walls with width of h = 1.0 nm. At either relatively low lateral pressure (PL ≤ 10 MPa) or relatively high lateral pressure (PL ≥ 400 MPa), the freezing of the confined water undergoes a first-order phase transition and gives rise to bilayer low-density amorphous (BL-LDA) ice and the trilayer puckered high-density ice (TL-pHDI), respectively. Very interestingly, within a moderate range of lateral pressures (100 MPa ≤ PL ≤ 300 MPa), the confined water appears to undergo a continuous phase transition in the isobaric condition to form a new phase, namely, the bilayer and puckered high-density amorphous (BL-pHDA) ice. A similar continuous phase transition behavior has been reported previously in tens of nanoseconds MD simulations of the freezing of BL water into the BL flat rhombic ice within a narrower hydrophobic nanoslit (h = 0.8 nm) and in the isochoric condition at high densities of water (Han et al. Nat. Phys. 2010, 6, 685). Our simulation results on the pressure-dependent continuous and first-order phase transitions of the confined water extend the previous study in a different way and thereby provide new insights into the novel thermodynamic phase behavior of low-dimensional water in nanoscale confinement.