Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment.

To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.

Hierarchical Gelation of a Pd12L24 Metal-Organic Cage Regulated by Cholesteryl Groups.

The creation of supramolecular assemblies by assembly of structurally simple components via supramolecular interactions provides an opportunity to develop functional materials with hierarchical complexibility. Herein, we report an assembly approach to supramolecular gels based on metal-organic cages with tunable hierarchical structures and properties. A Pd12L24 cage (L is cholesteryl-functionalized 3,5-bis(4-pyridyl)benzene) bearing 24 cholesteryl groups is used as a supramolecular building unit and molecular platform for functionalization with tunable functional behaviors. The Pd12L24 cage motifs spontaneously self-assemble into gels where orthogonal metal-organic coordination and cholesteryl-cholesteryl interactions are involved in the gelation. The Pd12L24 cage exhibits a reversible transition between solution and aggregated gel states in response to temperature. The gelation and the mechanical property are rarely regulated by deuterated solvents and tetramethylsilane. The mechanical property of the gel materials is tunable by varying the content of cholesteryl groups of Pd12L24. Functional moieties (e.g., luminescent TPE group) can be introduced on the cage, and the luminescent property changes while the structure is maintained. The Pd12L24 gel shows visible anion-responsive behaviors arising from the hierarchical structure.

Apple Fruit Recognition Algorithm Based on Multi-Spectral Dynamic Image Analysis.

The ability to accurately recognize fruit on trees is a critical step in robotic harvesting. Many researchers have investigated a variety of image analysis methods based on different imaging technologies for fruit recognition. However, challenges still occur in the implementation of this goal due to various factors, especially variable light and proximal color background. In this study, images with fruit were acquired with a Forward Looking Infrared (FLIR) camera based on the Multi-Spectral Dynamic Imaging (MSX) technology. In view of its imaging mechanism, the optimal timing and shooting angle for image acquisition were pre-analyzed to obtain the maximum contrast between fruit and background. An effective algorithm was developed for locking potential fruit regions, which was based on the pseudo-color and texture information from MSX images. The algorithm was applied to 506 training and 340 evaluating images, including a variety of fruit and complex backgrounds. Recognition precision and sensitivity of these complete fruit regions were both above 92%, and those of incomplete fruit regions were not lower than 72%. The average processing time for each image was less than 1 s. The results indicated that the developed algorithm based on MSX imaging was effective for fruit recognition and could be suggested as a potential method for the automation of orchard production.

Efficient Removal of Copper Ion from Wastewater Using a Stable Chitosan Gel Material.

: Gel adsorption is an efficient method for the removal of metal ion. In the present study, a functional chitosan gel material (FCG) was synthesized successfully, and its structure was detected by different physicochemical techniques. The as-prepared FCG was stable in acid and alkaline media. The as-prepared material showed excellent adsorption properties for the capture of Cu2+ ion from aqueous solution. The maximum adsorption capacity for the FCG was 76.4 mg/g for Cu2+ ion (293 K). The kinetic adsorption data fits the Langmuir isotherm, and experimental isotherm data follows the pseudo-second-order kinetic model well, suggesting that it is a monolayer and the rate-limiting step is the physical adsorption. The separation factor (RL) for Langmuir and the 1/n value for Freundlich isotherm show that the Cu2+ ion is favorably adsorbed by FCG. The negative values of enthalpy (ΔH°) and Gibbs free energy (ΔG°) indicate that the adsorption process are exothermic and spontaneous in nature. Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS) analysis of FCG before and after adsorption further reveal that the mechanism of Cu2+ ion adsorption. Further desorption and reuse experiments show that FCG still retains 96% of the original adsorption following the fifth adsorption-desorption cycle. All these results indicate that FCG is a promising recyclable adsorbent for the removal of Cu2+ ion from aqueous solution.

Effects of Ca addition on the uptake, translocation, and distribution of Cd in Arabidopsis thaliana.

Cadmium (Cd) pollution poses a risk to human health for its accumulation in soil and crops, but this can be alleviated by calcium (Ca) addition. However, its mechanism remains unclear yet. In this study, Arabidopsis thaliana was used to explore the alleviating effects of Ca on Cd toxicity and its specific function during uptake, upward-translocation, and distribution of Cd. Supplementing plants with 5mM CaCl2 alleviated the intoxication symptoms caused by 50µM CdCl2, such as smaller leaves, early bolting and root browning. Ca addition decreased uptake of Cd, possibly by reducing the physical adsorption of Cd since the root cell membrane was well maintained and lignin deposition was decreased as well, and by decreasing symplastic Cd transport. Expression of the genes involved (AtZIP2 and AtZIP4) was also decreased. In addition, Ca accumulated in the plant shoot to help facilitating the upward-translocation of Cd, with evidence of higher translocation factor and expression of genes that were involved in Ca transport (AtPCR1) and Cd xylem loading (AtHMA2 and AtHMA4). Dithizone-staining of Cd in leaves showed that in Cd+Ca-treated plants, Ca addition initially protected the leaf stomata by preventing Cd from entering guard cells, but with prolonged Cd treatment facilitated the Cd accumulation around trichomes and maybe its excretion. We conclude that Ca promotes the upward-translocation of Cd and changes its distribution in leaves. The results may have relevance for bioremediation.

[Status, problems and warranty strategy of quality uniformity for traditional Chinese medicine preparations].

The quality uniformity of traditional Chinese medicine (TCM) preparation is the base for guaranteeing the safety and effectiveness of clinical medication. At present, the quality of TCM preparation is uneven. At present, the same TCM preparation in different manufacturers, TCM preparations in the same manufacturer, and even different batches of a same TCM preparation in the same manufacturer have great differences in quality, which can not reach stability and uniformity. This paper would discuss the possible factors that influence the uniformity of quality in the whole process of pharmacy by means of consulting relevant literature on quality control of Chinese herbal preparations and analyzing the present situation and problems of the quality of TCM preparation. In addition, some strategies such as standardization of cultivation of TCM, processing standardization, standardization of pharmaceutical equipment, mixed batch feeding, and Quality by Design would be also put forward to provide references for the quality uniformity of TCM preparation.

Gelation of Luminescent Supramolecular Cages and Transformation to Crystals with Trace-Doped-Enhancement Luminescence.

Supramolecular gels with hierarchical order and complexity have been assembled. The gels contain well-defined Ag4L2 luminescent supramolecular cages as cores, which are cross-linked via Ag-P coordination bonding. The resulting gels are highly luminescent and exhibit rich stimuli-responsive behaviors toward mechanical and chemical (nitroexplosive and anions) stimuli. The gels could be transformed to highly luminescent crystal materials upon addition of halogen anions, in which only traces of lumiphor are accommodated in a host crystal matrix.

High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation.

AIM: High dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim of this study was to determine whether HDM exposure (area under the concentration vs. time curve, AUC), is significantly associated with transplant outcomes. METHODS: Melphalan concentrations were measured in six to 11 plasma samples collected after HDM (median 192 mg m(-) (2) ) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (≥ grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression-free survival and overall survival (OS). RESULTS: Melphalan AUC ranged from 4.9 to 24.6 mg l(-1)  h, median 12.84 mg l(-1) h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P = 0.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P = 0.001), with an estimated median survival of 8.50 years vs. 5.38 years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression-free survival. CONCLUSIONS: This large scale pharmacodynamic analysis of HDM demonstrates that high melphalan exposure is associated with improved survival, with an acceptable increase in transplant toxicity. These results suggest studies targeting a higher AUC are warranted in patients undergoing HDM and ASCT for myeloma.

The correction fluorescence inner filter effect using a single excitation and dual-emission fiber optic probe.

A significant disadvantage of fluorometry is the inner filter effect when the fluorophore concentration is high. A new simple fiber-optic probe was made to measure the concentration of fluorescent solutions. The proposed probe consists of one excitation fiber and two emission fibers. One emission fiber is parallel to the excitation fiber, and the other has a tilted angle with the excitation fiber. A numerical model was used to optimize the tilted angle and distance of the three fibers. There was a linear relationship between the fluorophore concentration and the ratio of the fluorescence intensity of the two emission fibers. Using our homemade probe, we measured Eosin Y, fluorescein and quinine sulfate solutions. The linear range of Eosin Y solution was up to 500 µM, which was approximately 7 times the range measured with a single emission probe. The results of fluorescein and quinine sulfate solutions also showed that the fluorescence intensity ratio method could correct the inner filter effect. The experimental results also indicated that the probe is robust when the excitation light fluctuates.

An H2S Sensor Based on Electrochemistry for Chicken Coops.

The recent modernization of the livestock industry lags behind the scale of the livestock industry, particularly in indoor environmental monitoring. In particular, the H2S gas concentration in chicken coops affects the growth and reproductive capacity of the chickens and threatens their health. Therefore, the research and development of a low-cost, environmentally friendly sensor that can achieve on-line monitoring of H2S gas has a notably important practical significance. This paper reports the design of an H2S gas sensor, with selection of an electrochemical probe with high accuracy and wide measurement range using the relatively mature technology of electrochemical sensors. Although the probe of the sensor is the main factor that affects the sensor accuracy, the probe must be combined with a specifically designed signal condition circuit that can overcome the lack of an electrode to satisfy the requirements for the interconnection and matching between the output signal and the test instrument. Because the output current of the electrochemical electrode is small and likely to be disturbed by noise, we designed signal-conditioning modules. Through the signal-conditioning circuit, the output signal of the current electrode can be converted into a voltage and amplified. In addition, we designed a power control module because a bias voltage is necessary for the electrode. Finally, after the calibration experiment, the accurate concentration of H2S gas can be measured. Based on the experimental analysis, the sensor shows good linearity and selectivity, comparatively high sensitivity, perfect stability and an extremely long operating life of up to two years.

Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging. AIM OF THE STUDY: To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 µM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs. RESULTS: After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention. The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress. Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis. The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385. CONCLUSIONS: ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.

Overexpression of keratin 17 is associated with poor prognosis in epithelial ovarian cancer.

The aim of this study was to investigate the association between keratin 17 (K17) expression and the clinicopathological features of patients with epithelial ovarian cancer (EOC). K17 expression was detected by real-time quantitative RT-PCR in EOC and adjacent noncancerous tissues. In addition, K17 expression was analyzed by immunohistochemistry in 104 clinicopathologically characterized EOC cases. The expression levels of K17 mRNA and protein in EOC tissues were both significantly higher than those in noncancerous tissues. In addition, positive expression of K17 correlated with the clinical stage (p=0.001). Furthermore, Kaplan-Meier survival analysis showed that a high expression level of K17 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis revealed that EOC expression level was an independent prognostic parameter for the overall survival rate of EOC patients. Our data are the first to suggest that increased K17 expression in EOC is significantly associated with aggressive progression and poor prognosis. K17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of EOC.

Application of resistance gene analog markers to analyses of genetic structure and diversity in rice.

Plant disease resistance gene analog (RGA) markers were designed according to the conserved sequence of known RGAs and used to map resistance genes. We used genome-wide RGA markers for genetic analyses of structure and diversity in a global rice germplasm collection. Of the 472 RGA markers, 138 were polymorphic and these were applied to 178 entries selected from the USDA rice core collection. Results from the RGA markers were similar between two methods, UPGMA and STRUCTURE. Additionally, the results from RGA markers in our study were agreeable with those previously reported from SSR markers, including cluster of ancestral classification, genetic diversity estimates, genetic relatedness, and cluster of geographic origins. These results suggest that RGA markers are applicable for analyses of genetic structure and diversity in rice. However, unlike SSR markers, the RGA markers failed to differentiate temperate japonica, tropical japonica, and aromatic subgroups. The restricted way for developing RGA markers from the cDNA sequence might limit the polymorphism of RGA markers in the genome, thus limiting the discriminatory power in comparison with SSR markers. Genetic differentiation obtained using RGA markers may be useful for defining genetic diversity of a suite of random R genes in plants, as many studies show a differentiation of resistance to a wide array of pathogens. They could also help to characterize the genetic structure and geographic distribution in crops, including rice, wheat, barley, and banana.

Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization.

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research. Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1. Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed. Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

The Effect of a Three-Level Remote Alliance on Critical Care in Grassroot Areas: A Multi-Center, Retrospective Study.

Purpose: To explore an effective model to promote the homogeneous development of intensive care units (ICUs) in grassroot, impoverished and remote areas. Methods: A three-level remote alliance model (in-place and online assistance) was adopted to guide the cross-talk of ICUs between counties and cities. The observed indicators included the mortality of ICU patients and those with APACHE II scores ≥15 points, deep vein thrombosis, ventilator-associated pneumonia, the completion rate of septic shock goals in 3-hour and 6-hour bundles, and the rates of patient transfers. Results: After the implementation of the remote alliance, there was significant reduction in the mortality of ICU patients in the county and city-level tertiary hospitals (7.6% vs 4.5%, P = 0.004; OR = 1.734, 95% CI 1.189-2.532) and the mortality rates of patients with APACHE II scores ≥15 points (11.9% vs 7.1%, P = 0.004; OR = 1.763, 95% CI 1.189-2.614). There was a significant reduction in the incidence of ventilator-associated pneumonia (0.9% vs 5.0%, P < 0.001) and deep vein thrombosis (52.4% vs 13.6%, P < 0.001). The completion rate of 3-hour bundle therapies for septic shock was significantly improved (95.7% vs 68.4%, P < 0.001), as well as 6-hour bundle therapies for septic shock (97.9% vs 81.6%, P < 0.001). The hospital transfer rate decreased significantly in the grassroots and impoverished areas (2.6% vs 4.7%, P < 0.001). Conclusion: A three-level remote alliance might be helpful in improving the quality of critical care in remote areas and promoting the homogeneous development of disciplines.

Shikonin Could Be Used to Treat Tubal Pregnancy via Enhancing Ferroptosis Sensitivity.

Background: Albeit oxidative stress has been implied in the pathogenesis of tubal pregnancy (TP), there are scant data to suggest that ferroptosis occurs in TP. Shikonin plays a pivotal role in redox status, but whether it can regulate ferroptosis to treat TP remains unknown. Methods: We collected and analyzed ferroptosis-related indices from the villous tissue (VT) of women suffering from TP and from women with a normal pregnancy. In vitro, we used shikonin and/or RAS-selective lethal 3 (RSL3) to intervene HTR-8/SVneo cells and further detected ferroptosis indices and cell functions. Finally, the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) is pharmacologically activated to explore the effect of Nrf2 on shikonin regulating ferroptosis. Results: Increased malondialdehyde content, reduced levels of glutathione and glutathione peroxidase (GPx), and upregulated protein expression which promoted ferroptosis were observed in the VT of TP patients, suggesting that ferroptosis occurred during TP. In vitro, shikonin enhanced ferroptosis sensitivity in HTR-8/SVneo cells induced by RSL3 via amplifying lipid peroxidation, which mainly included increasing cellular reactive oxygen species (ROS), lipid ROS and Fe2+ level. RSL3 and/or shikonin inhibited Nrf2 and downregulated protein expression of SLC7A11 and GPx4 caused by RSL3 + shikonin co-treatment, which could be reversed under activation of Nrf2. Hence, shikonin facilitated lipid peroxidation by inhibiting Nrf2 signaling. Additionally, shikonin and/or RSL3 potently inhibited the invasion and migration of HTR-8/SVneo cells. Conclusion: This study firstly showed that ferroptosis may be involved in TP pathogenesis and shikonin potentially targeted ferroptosis to treat TP.

Zuogui pills maintain the stemness of oogonial stem cells and alleviate cyclophosphamide-induced ovarian aging through Notch signaling pathway.

BACKGROUND: Zuogui pills (ZGP), a classical prescription of traditional Chinese medicine, have been widely used in the treatment of ovarian aging. Previous studies have demonstrated its efficacy on protecting ovarian aging, and the mechanisms were mostly relevant to inhibiting the apoptosis of follicles and activating the primordial follicles. However, whether ZGP could stimulate the oogonial stem cells (OSCs) to refresh the follicle pool remains poorly understood. PURPOSE: To investigate the effects of ZGP on the stemness of OSCs in cyclophosphamide (Cy)-induced ovarian aging. STUDY DESIGN AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into 8 groups: control group, model group, ZGP groups (low / high dose groups), estradiol valerate (EV) groups (low / high dose groups), DAPT group and DAPT+ZGP-L group. After modeling with Cy, the ZGP groups and EV groups were treated with ZGP and EV for 8 weeks respectively. Meanwhile, the DAPT groups were treated with DAPT twice a week. Additionally, OSCs were also isolated after modeling, and then treated with drug serum containing ZGP or EV. Ovarian volume and the ratio of weight of total ovaries to the body weight were measured. The serum hormones were measured by ELISA. Quantities and location of OSCs in ovaries were detected by flow cytometry and immunofluorescence. Cell viability was measured by CCK8. And OSCs were identified by immunofluorescence. Biomarkers of germ cells, stem cells and associated to differentiation and meiosis were detected by qPCR and western blot. Proteins in Notch signaling pathway were detected by western blot and immunofluorescence. RESULTS: After treating with ZGP, ovarian volume and the ratio of weight of total ovaries to the body weight increased. ZGP could increase serum AMH and E2 level and decrease serum FSH level. Quantities and cell viability of OSCs increased after ZGP treatment in vivo and in vitro. In addition, treatment with ZGP could increase not only the expression of MVH, Oct4 and DAZL, but also the expression of ZP1 and ZP2. Furthermore, ZGP could up-regulate the expression of Notch intracellular domain (NICD), HES1 and HES5. After blocking the Notch signaling pathway, ZGP could increase not only the expression of NICD, HES1 and HES5, but also the expression of MVH, Oct4, DAZL, ZP1 and ZP3. CONCLUSION: In conclusion, the mechanism of ZGP on treating ovarian aging may be relevant to maintain the stemness of OSCs by up-regulating Notch signaling pathway, which added the mechanism of ZGP on the perspective of OSCs at first time.

Mechanical forces on trophoblast motility and its potential role in spiral artery remodeling during pregnancy.

During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.

Research on the Mechanism of Asperosaponin VI for Treating Recurrent Spontaneous Abortion by Bioinformatics Analysis and Experimental Validation.

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.