Tryptophan in the mouse diet is essential for embryo implantation and decidualization.

Introduction: Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy. Methods: Embryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis. Results: On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization. Conclusions: Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.

Effect of Aurora kinase B on polyploidy and decidualization in mouse uterus.

RESEARCH QUESTION: Decidualization is critical to the establishment of mouse normal pregnancy. The fibroblast-like stromal cells in the process form polyploid multinucleated cells. Aurora kinase B (Aurora B) has previously been shown to regulate polyploidy in various cells. However, whether Aurora B regulates the formation of decidual cell polyploidization and its regulatory mechanisms remain poorly understood. DESIGN: Establish decidualization model of mouse primary endometrial stromal cells in vitro. Construct pseudopregnancy mouse models and delayed-activation mouse models. Detect Aurora B and polyploidization related genes in mouse uteri treated by Aurora B specific inhibitor Barasertib and CPT. RESULTS: In this study, we found that Aurora B was strongly expressed in endometrial stromal cells after implantation. Additionally, Aurora B was remarkably up regulated in the stromal cells of oil-induced deciduomoa and in vitro decidualization. As an Aurora B specific inhibitor, Barasertib significantly inhibits the mRNA expression of Prl8a2, a marker of mouse decidualization. Furthermore, the protein levels of p-Plk1, Survivin and p-Cdk1 were inhibited by Barasertib. CPT-induced DNA damage suppressed Aurkb (encodes Aurora B) expression, thus resulting in polyploidization. CONCLUSION: Our data shows that Aurora B is expressed in decidual stromal cells of implantation sites and plays a key role for mouse decidualization. The protein of Plk1, Survivn, and Cdk1 may participate in formation of decidual cell polyploidization during mouse decidualization.

NIR phosphorescent cyclometalated platinum (II) complexes with CAIX targeted and nuclear penetration as potent anticancer theragnostic agents.

Although cisplatin drugs have achieved great success in cancer therapy, they also easily cause drug resistance and other side effects. Non-classical platinum (II) complexes with targeted therapy characteristics have become one of the hotspots in the research of new anticancer drugs. In the present work, a series of carbonic anhydrase IX (CAIX)-targeted and inhibited cyclometalated platinum (II) complexes with near-infrared (NIR) phosphorescent emission have been developed, due to the calculation of Molecular docking and the result of CAIX inhibition assay in vitro, all complexes show a high binding affinity and effective inhibition on CAIX in vitro. Moreover, Pt2 shows a significant cellar uptake efficiency, and translocation of red emission in Pt2 from the cytoplasm to nuclear in Hela cell can be recorded by confocal within 24 h, while Pt2 can selectively target and locate in the lysosome of MDA-MB-231 cell, thus resulting in significantly enhanced therapeutic effect on multiple cancer cell lines compared with cisplatin, as well as the killing selectivity towards cancer cell of CAIX-inhibited cyclometalated platinum (II) complex are 6.0-14.6 times higher than that of cisplatin. Hence, our work presents the rational design of Pt (II)-CAIX conjugates as a promising strategy in the application of constructing a new platform for cancer theragnostic agents.

Trapping integrated molecular devices via local transport circulation.

Interactions between quantum systems and their environments may always result in inevitable decoherence. Isolation of the quantum system from the undesired environmental noise is a great challenge for ideal quantum information processing. Herein, based on a parallelly shaped control-target molecular nanomagnet structure, we report a novel strategy which decouples the target molecular device from its surrounding conduction baths. By tuning the level differences between the control and target orbitals through external gate voltages, one manipulates both, neither or only the target subsystem to contribute to the quantum transport in sequence, corresponding to an "on-off-on" behavior in the linear conductance. In the off window, a local transport circulation develops, preventing the target device from being disturbed by the itinerant electrons. This finding provides a prospective method for confining integrated quantum devices with high intrinsic fidelity, remarkable tunability, and universal suitability.

Effects of Aurora kinase A on mouse decidualization via Stat3-plk1-cdk1 pathway.

BACKGROUND: Decidualization is essential to the successful pregnancy in mice. The molecular mechanisms and effects of Aurora kinase A (Aurora A) remain poorly understood during pregnancy. This study is the first to investigate the expression and role of Aurora A during mouse decidualization. METHODS: Quantitative real time polymerase chain reaction, western blotting and in situ hybridization were used to determine the expression of Aurora A in mouse uteri. Aurora A activity was inhibited by Aurora A inhibitor to explore the role of Aurora A on decidualization via regulating the Aurora A/Stat3/Plk1/Cdk1 signaling pathway. RESULTS: Aurora A was strongly expressed at implantation sites compared with inter-implantation sites. Furthermore, Aurora A was also significantly increased in oil-induced deciduoma compared with control. Both Aurora A mRNA and protein were significantly increased under in vitro decidualization. Under in vitro decidualization, Prl8a2, a marker of mouse decidualization, was significantly decreased by TC-S 7010, an Aurora A inhibitor. Additionally, Prl8a2 was reduced by Stat3 inhibitor, Plk1 inhibitor and Cdk1 inhibitor, respectively. Moreover, the protein levels of p-Stat3, p-Plk1 and p-Cdk1 were suppressed by TC-S 7010. The protein levels of p-Stat3, p-Plk1 and p-Cdk1 were also suppressed by S3I-201, a Stat3 inhibitor). SBE 13 HCl (Plk1 inhibitor) could reduce the protein levels of p-Plk1 and p-Cdk1. Collectively, Aurora A could regulate Stat3/Plk1/Cdk1 signaling pathway. CONCLUSION: Our study shows that Aurora A is expressed in decidual cells and should be important for mouse decidualization. Aurora A/Stat3/Plk1/Cdk1 signaling pathway may be involved in mouse decidualization.

Kondo effect and RKKY interaction assisted by magnetic anisotropy in a frustrated magnetic molecular device at zero and finite temperature.

Molecular magnetic compounds, which combine the advantages of nanoscale behaviors with the properties of bulk magnetic materials, are particularly attractive in the fields of high-density information storage and quantum computing. Before molecular electronic devices can be fabricated, a crucial task is the measurement and understanding of the transport behaviors. Herein, we consider a magnetic molecular trimer sandwiched between two metal electrodes, and, with the aid of the sophisticated full density matrix numerical renormalization group (FDM-NRG) technique, we study the effect of magnetic anisotropy on the charge transport properties, illustrated by the local density of states (LDOS, which is proportional to the differential conductance), the Kondo effect, and the temperature and inter-monomer hopping robustness. Three kinds of energy peaks are clarified in the LDOS: the Coulomb, the Kondo and the Ruderman-Kittel-Kasuya-Yosida (RKKY) peaks. The local magnetic moment and entropy go through four different regimes as the temperature decreases. The Kondo temperature TK could be described by a generalized Haldane's formula, revealing in detail the process where the local moment is partially screened by the itinerant electrons. A relationship between the width of the Kondo resonant peak WK and TK is built, ensuring the extraction of TK from WK in an efficient way. As the inter-monomer hopping integral varies, the ground state of the trimer changes from a spin quadruplet to a magnetically frustrated phase, then to an orbital spin singlet through two first order quantum phase transitions. In the first two phases, the Kondo peak in the transmission coefficient reaches its unitary limit, while in the orbital spin singlet, it is totally suppressed. We demonstrate that magnetic anisotropy may also induce the Kondo effect, even without Coulomb repulsion, hence it is replaceable in the many-body behaviours at low temperature.

Tryptophan and kynurenine stimulate human decidualization via activating Aryl hydrocarbon receptor: Short title: Kynurenine action on human decidualization.

Decidualization is essential for successful pregnancy in rodents and primates. Although L-Tryptophan and its metabolites are essential for mammalian pregnancy, the underlying mechanism is poorly defined. We explored effects of tryptophan and kynurenine on human in vitro decidualization in human endometrial stromal cell line and primary endometrial stromal cells. Tryptophan significantly stimulates the expression of prolactin and insulin growth factor binding protein 1, reliable markers for human decidualization. When stromal cells are treated with tryptophan, tryptophan hydroxylase-1 remains unchanged, but indoleamine 2,3-dioxygenase 1 is significantly increased, suggesting tryptophan is mainly metabolized through kynurenine pathway. Kynurenine significantly stimulates insulin growth factor binding protein 1 expression. Aryl hydrocarbon receptor and its target genes (P450 1A1 and P450 1B1) are significantly increased by tryptophan and kynurenine. The induction of tryptophan and kynurenine on insulin growth factor binding protein 1 is abrogated by CH223191, an aryl hydrocarbon receptor inhibitor. Cytochrome P450 1A1 and P450 1B1 catalyze the oxidative metabolism of estradiol to catechol estrogens (2-hydroxy estradiol and 4-hydroxy estradiol), respectively. Insulin growth factor binding protein 1 is up-regulated by 2-hydroxy estradiol and 4-hydroxy estradiol. Interferon-γ significantly induces the expression of indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor and insulin growth factor binding protein 1. All the data are also verified in primary human stromal cells. Our data indicate that Interferon-γ-induced kynurenine pathway promotes human decidualization via aryl hydrocarbon receptor signaling.

MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene.

Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA-363 (miR-363) affects the development of RCC via the Janus tyrosine kinases (JAK2)-signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR-363 mimic, miR-363 inhibitor, or small interfering RNA against GHR to determine the influence of miR-363 on the expression of GHR and JAK2-STAT3 axis-related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), wound-healing, and Transwell assays. The results revealed reduced miR-363 expression and elevated GHR expression in RCC. It was also found that miR-363 altered the activation of the JAK2-STAT3 axis through the inhibition of GHR. Cells treated with the miR-363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR-363. These results implicated that the overexpression of miR-363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2-STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.

Expression and localization of GPR143 in sheep skin.

G-protein coupled receptor143 (GPR143) plays an important role in melanogenesis. In this study, we investigated the expression pattern and localization of GPR143 in skin of sheep with different coat colors and explored the correlation between GPR143 gene and coat color. The mRNA level and protein level of GPR143 in skin of sheep with different coat colors were detected by qRT-PCR and immunoblotting separately while the localization of GPR143 in sheep skin was detected by immunofluorescence assay following optical density analysis. The qRT-PCR results showed that the relative expression level of GPR143 mRNA in black sheep skin was 7.84 times of that in white sheep skin (P<0.01). Immunoblotting results demonstrated that the expression level of GPR143 protein in black sheep skin was 1.30 times of that in white sheep skin (P<0.05). Immunofluorescence assay revealed that GPR143 was primarily expressed in the outer root sheath of hair follicles and epidermal skin tissue. Optical density analysis showed that expression levels of GPR143 in the outer root sheath and epidermis of black sheep skin were significantly higher than that of white sheep skin. Our studies demonstrated that GPR143 is expressed in skin of sheep with different coat colors. However, the mRNA and protein levels of GPR143 in black sheep skin are significantly higher than that in white sheep skin, indicating that GPR143 mRNA and protein levels are upregulated in skin of black sheep while downregulated in skin of white sheep. GPR143 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of the melanosome.

Novel perfusion-decellularized method to prepare decellularized ureters for ureteral tissue-engineered repair.

As the endoscopic technique is widely used in the diagnosis and treatment of diseases, the incidence of ureteral injuries increases annually. The classical surgical therapies are not always satisfactory. With the constant development of the tissue engineering technology in the field of urinary reconstruction, the ureteral reconstruction has become possible technology. In this study, a novel perfusion-decellularized protocol, which combined a perfusion system with the commonly used physical and chemical methods, was used to prepare the decellularized ureters for ureteral reconstruction and the urinary tract-derived cells (UDCs) were seeded on the surface of the perfusion-decellularized ureters (PDUs) in order to observe the cells survival, adhesion, proliferation and distribution. The data of H&E staining, DAPI staining, and the agarose gel electrophoresis demonstrated that the cellular components of PDUs were removed, and the decellularized time was shorter than previous study. In addition, compared with the native ureters, the DNA content of the PDUs was significantly decreased just two percent residue (P<0.05). Scanning electron microscopy, collagen and glycosaminoglycan content assay showed that the three-dimensional (3D) ultrastructure and the compositions of the extracellular matrix (ECM) of PDUs were well preserved. When the UDCs were seeded onto the PDUs, the UDCs formed multilayer structure on the surface of the PDUs, infiltrated into the deep layer of the decellularized ureters and then formed laminated structure. In conclusion, the decellularized ureters prepared by the novel perfusion-decellularized method may be the potential surrogate for ureteral tissue-engineered repair.

[A perfusion system for preparing canine ureteral acellular matrix].

OBJECTIVE: To explore the feasibility of preparing ureteral acellular matrix (UAM) using perfusion systems. METHODS: Using the luminal structure of the ureter, the UAM was prepared by perfusing canine ureter with SDS, TritonX-100, or both. The residual nuclei in the UAM were evaluated using HE staining, DAPI staining, DNA quantification, and agarose gel electrophoresis. The three-dimensional ultrastructure and the bioactive components were evaluated by Masson's trichrome staining, Alcian Blue staining, collagen quantification, GAG quantification, scanning electron microscopy (SEM), and toxicity detection. RESULTS: HE staining and DAPI staining showed the absence of obvious nuclear materials in the combined group, which was further confirmed by DNA quantification and agarose gel electrophoresis. Masson's trichrome staining, Alcian Blue staining, collagen quantification and GAG quantification all verified that the ultrastructure and the bioactive components were well preserved in the combined group. SEM showed a large amount of porous structure on the surface of the UAM prepared by combined perfusion, and toxicity assay confirmed that the prepared UAM was nontoxic. CONCLUSION: Perfusion of canine ureter with SDS and TritonX-100 is feasible to prepare UAM for ureteral reconstruction.

[Ecological adaptability evaluation of peanut cultivars based on biomass and nutrient accumulation].

To identify the good peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability, 19 selected peanut cultivars were planted in the low champaign area and piedmont plain area of Hebei Province. By using principal component analysis, the adaptability of these 19 cultivars was evaluated for different ecological regions through comparing their 16 main traits including biomass and nutrient parameters. According to the critical value of principal component (>1.0), the 16 biomass and nutrient characteristics were integrated into 4 principal components which accounted for 85% of the original information. The results indicated that there were obvious differences in yield and nutrient use efficiency for the peanut cultivars in different ecological regions. The 19 peanut cultivars were classified into 2 groups according to their ecological adaptability, and the cultivars from the group with wide adaptability could further be divided into 3 categories according to their yield and nutrient use efficiency. Among these cultivars, Yuhua 9719, Jihua 0212-4, Weihua 10, Yuhua 15, Puhua 28 and Jihua 10 were selected as the better peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability.

[Immobilization remediation of Cd and Pb contaminated soil: remediation potential and soil environmental quality].

A pot experiment was conducted to investigate the immobilization remediation effects of sepiolite on soils artificially combined contamination by Cd and Pb using a set of various pH and speciation of Cd and Pb in soil, heavy metal concentration in Oryza sativa L., and soil enzyme activity and microbial quantity. Results showed that the addition of sepiolite increased the soil pH, and the exchangeable fraction of heavy metals was converted into Fe-Mn oxide, organic and residual forms, the concentration of exchangeable form of Cd and Pb reduced by 1.4% - 72.9% and 11.8% - 51.4%, respectively, when compared with the control. The contents of heavy metals decreased with increasing sepiolite, with the maximal Cd reduction of 39.8%, 36.4%, 55.2% and 32.4%, respectively, and 22.1%, 54.6%, 43.5% and 17.8% for Pb, respectively, in the stems, leaves, brown rice and husk in contrast to CK. The addition of sepiolite could improve the soil environmental quality, the catalase and urease activities and the amount of bacteria and actinomycete were increased to some extents. Although the fungi number and invertase activity were inhibited compared with the control group, it was not significantly different (P > 0.05). The significant correlation between pH, available heavy metal content, urease and invertase activities and heavy metal concentration in the plants indicated that these parameters could be used to evaluate the effectiveness of stabilization remediation of heavy metal contaminated soil.