Abiotic transformation of synthetic progestins in representative soil mineral suspensions.

Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while their fate in soil minerals remains unclear. This study explored the transformation of these progestins in MnO2, SiO2, and ferrihydrite suspensions and identified their transformation products (TPs) via high resolution mass spectrometry and density functional theory calculations. Transformations were only observed for DRO and MLA in SiO2 suspension and ALT in MnO2 suspension (half-lives = 0.86 min - 9.90 day). ALT transformation was facilitated at higher MnO2 loadings, while DRO and MLA transformations were inhibited at higher SiO2 loadings. These data indicated that hydrophobic partitioning interaction was dominant at higher SiO2 loadings rather than specific interaction, which limited subsequent surface-catalyzed transformation. ALT transformation rate decreased with increasing pH because MnO2 reduction requires proton participation. In contrast, relatively high pH facilitated MLA and DRO transformation, indicating that base-catalyzed hydrolysis occurred in SiO2 suspension. The clustermap demonstrated the formation of abundant TPs. Lactone ring and acetoxy group hydrolysis was the major transformation pathway for DRO and MLA, with estimated yields of 57.7% and 173.2% at 6 day, respectively. ALT experienced C12 hydroxylation and formed the major TP 326g (yield of 15.4% at 8 hr). ALT also experienced allyl group oxidation and subsequent C5 hydroxylation, forming the major TP 344a (yield of 14.1% at 8 hr). This study demonstrates that TPs of metastable progestins are likely the main species in soils and that TP identification is a particular priority for risk assessment.

Two-dimensional hexagonal chromium chalco-halides with large vertical piezoelectricity, high-temperature ferromagnetism, and high magnetic anisotropy.

On the basis of density functional theory, we predicted that Janus CrTeI and CrSeBr monolayers possess highly energetic, dynamical, and mechanical stability. Due to noncentral symmetry, the two monolayers exhibit vertical piezoelectricity with large piezoelectric coefficients d31 (1.745 and 1.716 pm V-1 for CrBSe and CrTeI, respectively), which are larger than those of most materials in existence. Both systems are also ferromagnetic (FM) semiconductors, with Curie temperature (TC) higher than 550 K and large in-plane magnetic anisotropy energy. Superexchange interactions are responsible for high-temperature FM order. A semiconductor to half metal transition can be regulated by carrier doping, which can be carried out by gate voltages. Doped systems still retain the same FM order as pristine ones; in particular, hole doping enhances exchange coupling, thereby increasing TC. The combination of piezoelectricity, high TC, and controllable electronic structures and magnetic properties makes magnetic 2D Janus CrSeBr and CrTeI attractive materials for potential applications in nanoelectronics, electromechanics, and spintronics.

Effects of hyaluronic acid on differentiation of human amniotic epithelial cells and cell-replacement therapy in type 1 diabetic mice.

Our hypothesis is that hyaluronic acid may regulate the differentiation of human amniotic epithelial cells (hAECs) into insulin-producing cells and help the treatment of type 1 diabetes. Herein, a protocol for the stepwise in vitro differentiation of hAECs into functional insulin-producing cells was developed by mimicking the process of pancreas development. Treatment of hAECs with hyaluronic acid enhanced their differentiation of definitive endoderm and pancreatic progenitors. Endodermal markers Sox17 and Foxa2 and pancreatic progenitor markers Pax6, Nkx6.1, and Ngn3 were upregulated an enhanced gene expression in hAECs, but hAECs did not express the ß cell-specific transcription factor Pdx1. Interestingly, hyaluronic acid promoted the expression of major pancreatic development-related genes and proteins after combining with commonly used inducers of stem cells differentiation into insulin-producing cells. This indicated the potent synergistic effects of the combination on hAECs differentiation in vitro. By establishing a multiple injection transplantation strategy via tail vein injections, hAECs transplantation significantly reduced hyperglycemia symptoms, increased the plasma insulin content, and partially repaired the islet structure in type 1 diabetic mice. In particular, the combination of hAECs with hyaluronic acid exhibited a remarkable therapeutic effect compared to both the insulin group and the hAECs alone group. The hAECs' paracrine action and hyaluronic acid co-regulated the local immune response, improved the inflammatory microenvironment in the damaged pancreas of type 1 diabetic mice, and promoted the trans-differentiation of pancreatic α cells into ß cells. These findings suggest that hyaluronic acid is an efficient co-inducer of the differentiation of hAECs into functional insulin-producing cells, and hAECs treatment with hyaluronic acid may be a promising cell-replacement therapeutic approach for the treatment of type 1 diabetes.

Sorption and desorption of seven steroidal synthetic progestins in five agricultural soil-water systems.

Manure fertilization and wastewater irrigation can introduce the biologically potent synthetic progestins into agricultural soils, causing endocrine disruption in organisms of nearby surface waters. Therefore, this study investigated the sorption and desorption potential of etonogestrel, medroxyprogesterone, gestodene, norgestrel, cyproterone acetate, levonorgestrel, and dienogest in five agricultural soil-water systems. Sorption data were well-described by the linear sorption model. In most batch systems, cyproterone acetate exhibited the highest affinities for soils, followed by etonogestrel, medroxyprogesterone, levonorgestrel, gestodene, norgestrel, and dienogest. The sorption magnitudes (logKoc or logKd) were significantly correlated with the progestin hydrophobicities (R2 = 0.72-0.86, p < 0.05). The Kd values of the progestins were also significantly correlated with organic carbon content and pore volumes of the soils (R2 = 0.68-0.98, p < 0.05). In addition, 0.5 M urea resulted in 3-19% decreases in Kd values of the progestins. Taken together, these data indicated that hydrophobic partitioning interaction, hydrogen bonding interaction, and pore filling were the sorption mechanisms for the progestins in soil-water systems. No significant desorption hysteresis was observed for the progestins, indicating that they can be readily desorbed under rainfall or irrigation events. Based on the sorption and desorption data, we estimated the dynamic transport of the progestins in conventional agricultural management systems, and predicted the concentrations of the progestins as a function of soil-sorbed concentration, water-soil ratio, and dilution factor of receiving waters. This study will improve the understanding of the risks posed by the progestins under field-scale hydrological conditions.

Hyaluronic acid enhances proliferation of human amniotic mesenchymal stem cells through activation of Wnt/ß-catenin signaling pathway.

This study investigated the pro-proliferative effect of hyaluronic acid (HA) on human amniotic mesenchymal stem cells (hAMSCs) and the underlying mechanisms. Treatment with HA increased cell population growth in a dose- and time-dependent manner. Analyses by flow cytometry and immunocytochemistry revealed that HA did not change the cytophenotypes of hAMSCs. Additionally, the osteogenic, chondrogenic, and adipogenic differentiation capabilities of these hAMSCs were retained after HA treatment. Moreover, HA increased the mRNA expressions of wnt1, wnt3a, wnt8a, cyclin D1, Ki-67, and ß-catenin as well as the protein level of ß-catenin and cyclin D1 in hAMSCs; and the nuclear localization of ß-catenin was also enhanced. Furthermore, the pro-proliferative effect of HA and up-regulated expression of Wnt/ß-catenin pathway-associated proteins - wnt3a, ß-catenin and cyclin D1 in hAMSCs were significantly inhibited upon pre-treatment with Wnt-C59, an inhibitor of the Wnt/ß-catenin pathway. These results suggest that HA may positively regulate hAMSCs proliferation through regulation of the Wnt/ß-catenin signaling pathway.

Long-term Effectiveness of Modified Electroconvulsive Therapy Compared With Repetitive Transcranial Magnetic Stimulation for the Treatment of Recurrent Major Depressive Disorder.

This retrospective study recruited 150 patients with recurrent major depressive disorder (MDD) who received modified electroconvulsive therapy (MECT) and 150 cases treated with repetitive transcranial magnetic stimulation (rTMS), which aimed to compare the short- and long-term effectiveness, as well as economic outcomes, of MECT and rTMS with a large sample size in patients with recurrent MDD. The results showed that the response rate of patients in the rTMS group was lower than that in the MECT group (46.0% vs 58.7%, p < 0.05). Patients in the rTMS group had elevated rate of dizziness, but reduced rates of poor memory and headache, as well as lower costs compared with the MECT group (p < 0.05). Importantly, we found that the relapse-free survival of patients was similar between the rTMS and MECT groups in the long term. In conclusion, rTMS is an alternative method for MECT in the treatment of patients with recurrent MDD.

Downregulation of caveolin-1 in chronic rhinosinusitis with and without nasal polyps.

The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding protein and plays a pivotal role in host defense against infections and tumour suppression by reducing production of cyclin D1 and endothelial nitric oxide-synthase (eNOS). However, little is known about their roles in CRS. Therefore, we aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein expression were investigated by immunohistochemistry method and mRNA expression of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction in CRS and control subjects. Moreover, the effects of various stimulators with different concentrations and time on Cav-1 were evaluated on nasal explant culture. The results showed that weaker expression of Cav-1 protein and mRNA were observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was augmented by IFN-γ, but supressed by IL-4 and IL-1ß. In conclusion, the expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN-γ may be essential for Cav-1 gene expression.

Viologen-mediated assembly of and sensing with carboxylatopillar[5]arene-modified gold nanoparticles.

Carboxylatopillar[5]arene (CP[5]A), a new water-soluble macrocyclic synthetic receptor, has been employed as a stabilizing ligand for in situ preparation of gold nanoparticles (AuNPs) to gain new insights into supramolecular host-AuNP interactions. CP[5]A-modified AuNPs with good dispersion and narrow size distributions (3.1 ± 0.5 nm) were successfully produced in aqueous solution, suggesting a green synthetic pathway for the application of AuNPs in biological systems. Supramolecular self-assembly of CP[5]A-modified AuNPs mediated by suitable guest molecules was also investigated, indicating that the new hybrid material is useful for sensing and detection of the herbicide paraquat.

Mechanized silica nanoparticles based on pillar[5]arenes for on-command cargo release.

Mechanized silica nanoparticles, equipped with pillar[5]arene-[2]pseudorotaxane nanovalves, operate in biological media to trap cargos within their nanopores, but release them when the pH is lowered or a competitive binding agent is added. Although cargo size plays an important role in cargo loading, cargo charge-type does not appear to have any significant influence on the amount of cargo loading or its release. These findings open up the possibility of using pillar[n]arene and its derivatives for the formation of robust and dynamic nanosystems that are capable of performing useful functions.

Knowledge, attitudes, and practice of pelvic floor dysfunction and pelvic floor ultrasound among women of childbearing age in Sichuan, China.

Objective: Pelvic floor dysfunction (PFD) is highly prevalent among women. Pelvic floor ultrasound (PFU) is a critical method for assessing PFD. This study examined the knowledge, attitudes, and practice (KAP) of women of childbearing age regarding PFD and PFU. Methods: This cross-sectional study was conducted between August 18, 2022, and September 20, 2022, in Sichuan, China. A total of 504 women of childbearing age participated in this study. A self-administered questionnaire was developed to assess KAP regarding PFD and PFU. Univariable and multivariable logistic regression analyses were conducted to assess the association between demographic characteristics and KAP. Results: The average scores for knowledge, attitudes, and practice were 12.53, 39.98, and 16.51 out of 17, 45, and 20, respectively. Despite adequate knowledge of PFD symptoms, aging-related risks, and PFD harms (correct rates > 80%), participants showed poor knowledge about the benefits of PFU, PFU types, and Kegel exercise (correct rates < 70%). High scores in knowledge and attitude (odds ratio = 1.23 and 1.11, P < 0.001 and P = 0.005, respectively) were independent predictors of good practice, while never having been pregnant (odds ratio = 0.10, P < 0.001), alcohol consumption (odds ratio = 0.09, P = 0.027), and not being diagnosed with PFD or an unclear diagnosis independently predicted poor practice (both odds ratio = 0.03, both P < 0.001). Conclusion: Women of childbearing age in Sichuan, China, showed moderate knowledge, positive attitude, and good practice regarding PFD and PFU. Knowledge, attitude, pregnancy history, alcohol consumption, and PFD diagnosis are associated with practice.

One-pot synthesis of pillar[n]arenes catalyzed by a minimum amount of TfOH and a solution-phase mechanistic study.

A practical and effective trifluoromethanesulfonic acid (TfOH)-catalyzed cyclooligomerization strategy was developed for the synthesis of functionalized pillar[n]arenes and copillar[5]arenes from 1,4-dialkoxybenzenes with paraformaldehyde under mild reaction conditions, and the reaction mechanism of solution-phase catalytic synthesis of pillararenes was investigated by room-temperature X-band ESR spectroscopy, mass spectroscopy, NMR and control experiments, suggesting a free radical process initially and a Friedel-Crafts alkylation process during the consequent coupling and ring-closure stage.

Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model.

Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC(50) values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.

Jiangxienone, a new compound with potent cytotoxicity against tumor cells from traditional Chinese medicinal mushroom Cordyceps jiangxiensis.

A new compound, named jiangxienone, has been isolated from a culture of the traditional Chinese medicinal mushroom Cordyceps jiangxiensis, and its chemical structure was established on the basis of spectroscopic and chemical techniques. Jiangxienone showed potent cytotoxic effects against human gastric adenocarcinoma SGC-7901 cell and human lung carcinoma A549 cell with IC(50) values ranging from 1.38 to 2.93 µM, i.e., with at least approximately six-fold stronger cytotoxicity than cisplatin, a first-line chemotherapy drug for cancer patients.

Occurrence and distribution of natural and synthetic progestins, androgens, and estrogens in soils from agricultural production areas in China.

The occurrence of biologically potent sex hormones in agricultural soils is of growing concern due to their ability to disrupt the endocrine systems of aquatic organisms after being transported to surface waters via runoff. This study, therefore, examined the large-scale occurrence of 34 natural and synthetic sex hormones (13 progestins, 16 androgens, and 5 estrogens) in soils from 7 provinces and 1 municipality in China. The target sex hormones were detected in 99.3% of the soil samples, indicating their widespread occurrence in most agricultural areas. Additionally, seven synthetic progestins were detected in soils for the first time. The total concentration of the 34 sex hormones (Σsex hormones) in the sampled soils ranged from below the method detection limit to 23.7 ng/g (mean of 4.72 ± 4.07 ng/g), with androgens and progestins being the most dominant hormone groups. Significant correlations were observed among the concentrations of Σestrogens, Σandrogens, and Σprogestins (r = 0.117-0.433, p < 0.001), suggesting similar sources of sex hormones. The mean concentration of Σsex hormones varied considerably across the selected provinces/municipality. Notably, the annual slaughter of poultry and swine (R2 = 0.75-0.88), female population (R2 = 0.57-0.58), and soil organic carbon content (R2 = 0.20-0.55) in each province were significantly correlated with the concentrations or mean concentrations of Σsex hormones, Σestrogens, or Σprogestins. This finding implies that these parameters contributed to the occurrence and distribution of sex hormones in the studied soils. Finally, risk quotients for some sex hormones exceeded 0.01, indicating medium or high risks to agroecosystems. This study highlights the importance of designing an optimal manure fertilization strategy in order to mitigate the risks posed by sex hormones in agroecosystems.

Sorption, transport, and transformation of natural and synthetic progestins in soil-water systems.

Natural and synthetic progestins are emerging endocrine disruptors that can be transported from livestock farms and agricultural fields to receiving waters via surface runoff. The transformation of progestins during transport is expected to affect the efficiencies of runoff management systems. Therefore, this study explored the sorption, transport, and transformation of progesterone, norethisterone acetate, medroxyprogesterone acetate, cyproterone acetate, dydrogesterone, and norethisterone in agricultural soil-water systems. The sorption coefficients and retardation factors (R) were positively correlated with the progestin hydrophobicities, indicating that hydrophobic interactions dominated the sorption and transport processes. During transport, dydrogesterone and progesterone were transformed into 9-10 products. The breakthrough curves of the parents and products exhibited periodical patterns over extended times. Specifically, the R values of the parents and products were positively correlated with chromatographic retention times (hydrophobicities) when the products were generated before transport. In contrast, a negative correlation (R2 = 0.75-0.88) was observed when products were successively generated during transport, indicating that the transformation kinetics changed the retardation of these solutes in the columns. These observations also demonstrated that the transport potential estimates based on traditional metrics of steroid hydrophobicity are not always accurate and that runoff management measures are less effective for metastable progestins.

Hyaluronic acid promotes osteogenic differentiation of human amniotic mesenchymal stem cells via the TGF-ß/Smad signalling pathway.

AIMS: This study investigated the effects of hyaluronic acid (HA), a commonly used osteogenic medium referred to as DAG, and the combined administration of HA and DAG (CG) on the osteogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs), and the underlying mechanism. MAIN METHODS: The phenotype of hAMSCs was detected by flow cytometry and immunocytochemical staining. Alkaline phosphatase (ALP) and calcium deposition assays were employed for evaluating the osteogenic differentiation of hAMSCs. The expression of osteogenesis-related genes and proteins was determined by quantitative reverse transcription PCR (qRT-PCR) and Western blotting, respectively. Meanwhile, the molecular mechanism of osteogenic differentiation of hAMSCs was detected by PCR array and qRT-PCR. KEY FINDINGS: The results showed that treatment with CG could significantly stimulate hAMSC ALP activity and calcium deposition compared to treatment with DAG, while HA had little effect. The expression of osteogenesis-related molecules and stemness-related molecules was up-regulated at the mRNA and protein levels in all three groups, and this up-regulation was most significant in the CG group. In addition, treatment with CG significantly increased the gene expressions involved in regulation of the TGF-ß/Smad signalling pathway compared to treatment with DAG. Furthermore, the pro-osteogenic differentiation effects as well as the up-regulated expression of genes observed in the CG treatment group were significantly inhibited when the cells were pre-treated with SB431542, an inhibitor of the TGF-ß/Smad pathway. SIGNIFICANCE: These results suggest that HA in combination with DAG could significantly enhance the osteogenic differentiation of hAMSCs, potentially via the TGF-ß/Smad signalling pathway.

[Epidemiological investigation of Angiostrongylus cantonensis in Jiangmen of Guangdong Province].

OBJECTIVE: To make an epidemiological survey on Angiostrongylus cantonensis in Jiangmen City of Guangdong Province. METHODS: From October 2006 to November 2007, the characteristics of A. cantonensis infection were investigated in Jiangmen district in various hosts, including the third stage larva infection in the snails Achatina fulica and Pomacea canaliculata by digestion method, and the adult A. cantonensis in rats by the dissection of heart and lungs. Relevant symptoms and dietary habits in Jiangmen residents who were randomly recruited were also investigated by questionnaire, and the specific IgG and IgM antibodies against A. cantonensis in their sera were detected by ELISA. RESULTS: 695 A. fulica and 720 P. canaliculata were examined. The infection rate of third stage larva of A. cantonensis were 45.0% and 1.8% respectively, with an infectivity of 53.74+/-147.30 and 5.23+/-8.51 respectively. Natural infection rate of A. cantonensis in all 229 rats was 4.4%. Among the 300 people surveyed, 11.3% had a history of eating raw or undercooked fish and shrimp, 5.3% directly or indirectly exposed to A. fulica or P. canaliculata. The positive rate of specific IgG antibody against A. cantonensis for serum samples among residents was 14.0% (42/300), and 5 serum samples in the 42 positive samples showed specific IgM antibody, with a positive rate of 1.7%. CONCLUSION: Jiangmen district is an endemic area of A. cantonensis, and the local residents are under the risk of infection.

[Investigation on antitumor mechanism of polysaccharide from medicinal fungus Penicillium jiangxiense].

OBJECTIVE: To investigate the possible antitumor mechanism of polysaccharide from medicinal fungus Penicillium jiangxiense. METHODS: The cytotoxic effect was measured by MTT assay, and the cell cycle was analyzed by flow cytometry with Propidium iodide (PI) staining. To apoptotic detections, Hoechst 33258 staining for chromatin, annexin-V FITC/PI double staining for early phase cell apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) for late phase cell apoptosis. RESULTS: Both MPPJ4 and MPPJ5, the fine polysaccharide fractions from P. jiangxiense, showed slight cytotoxic effects to inhibit human gastric adenocarcinoma SGC-7901 cells proliferation, but significantly caused cell cycle arrest at the S phase, and the rate of cell population at the subG1 phase was evidently increased. In apoptotic assays, MPPJ5 was more potent than MMPJ4 in inducing tumor cells in a time-dependent manner at the range from 0 to 72 hours, comparable to the negative control. CONCLUSION: The antitumor acting mechanism of P. jiangxiense polysaccharide is associated with the induction of apoptotic cell death and cell cycle arrest.

Synergistic antitumor efficacy of antibacterial helvolic acid from Cordyceps taii and cyclophosphamide in a tumor mouse model.

The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the in vivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) - a well-known chemotherapy drug - showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of ß-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent in vivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ ß-catenin signaling pathway.