Giant tunnel resistance effect in (SrTiO3)2/(BaTiO3)4/(CaTiO3)2 asymmetric superlattice with enhanced polarization.

In this work, we report the effectively enhanced tunneling electroresistance effect in Au/(SrTiO3)2/(BaTiO3)4/(CaTiO3)2/Nb:SrTiO3 superlattice ferroelectric tunnel junction (FTJ). The stable polarization switching and enhanced ferroelectricity were achieved in the nanoscale thickness high-quality epitaxial superlattice. A high ON/OFF current ratio of more than 105 was obtained at room temperature, which is an order of magnitude larger than the BaTiO3 FTJ with the same structure. Nonvolatile resistance switching controlled by nonvolatile polarization switching was observed in the superlattice FTJ. Driven by increased polarization and intrinsic asymmetric ferroelectricity, a highly asymmetric depolarization field is generated compared with the Au/BaTiO3/Nb:SrTiO3 FTJ, resulting in an enhanced tunneling electroresistance effect. These results provide a potential way to construct FTJ memory devices by constructing asymmetric three-component ferroelectric superlattices.

Euploid blastocyst rates in patients from POSEIDON groups 3 and 4 using propensity score matching.

RESEARCH QUESTION: Do patients with low ovarian reserve, as defined by the patient-oriented strategies encompassing individualized oocyte number (POSEIDON) criteria, have low euploid blastocyst rates? DESIGN: Retrospective study of 548 IVF cycles of patients with unexplained recurrent miscarriage who underwent preimplantation genetic test for aneuploidy (PGT-A). Euploid blastocyst rates were analysed to compare patients from POSEIDON groups 3 and 4 (serum anti-Müllerian hormone [AMH] levels <1.2 ng/ml) with those who have normal ovarian reserve (AMH levels ≥1.2 ng/ml) before and after using propensity score matching to match selected variables, such as female age, body mass index, the number of clinical miscarriages, ovarian stimulation protocols and PGT-A analysis platforms. Cycles of patients from POSEIDON groups 3 and 4 were then divided into four groups according to median and quartiles of serum AMH levels: <0.668 ng/ml, 0.668-0.890 ng/ml, >0.890-1.070 ng/ml and >1.070-<1.20 ng/ml. The euploid blastocyst rates were compared across these four groups. RESULTS: After using propensity score matching, no difference was found in euploid blastocyst rates between patients from POSEIDON groups 3 and 4 and those with normal ovarian reserve. Among cycles of patients from POSEIDON groups 3 and 4, no difference was found in euploid blastocyst rates between the different AMH levels. CONCLUSIONS: The decline in ovarian reserve in patients from POSEIDON groups 3 and 4 was not related to low euploid blastocyst rates. Serum AMH levels do not seem to be a predictor of euploid blastocyst rates in such patients.

Differential transcriptional profiles of human cumulus granulosa cells in patients with diminished ovarian reserve.

PURPOSE: This study compared the gene expression profiles of cumulus granulosa cells in patients with diminished ovarian reserve and those with normal ovarian reserves to identify genes that may be involved in the pathogenesis of diminished ovarian reserve. METHODS: After retrieval of the cumulus-oocyte complex, the cumulus granulosa cells that surrounded the oocytes of 25 patients with diminished ovarian reserve and 25 patients with normal ovarian reserves were removed by mechanical stripping. Extraction of RNA from the cumulus granulosa cells was for RNA sequencing and analysis. RT-PCR was used to confirm the candidate genes. Statistical analysis was performed using student's t test. RESULTS: A total of 294 upregulated genes and 336 downregulated genes were identified in the POSEIDON patients relative to the normal ovarian reserve group. Bioinformatic analysis showed that the downregulated genes were highly enriched in the Wnt signaling pathway, negative regulation of stress fiber assembly, and cell chemotaxis, while the upregulated genes were highly enriched in functions associated with the regulation of interleukin-5 production and regulation of immune system processes. According to the differential expression levels and their potential functions, IL1RL1, IL33, SFRP4, and S1PR1 were validated by quantitative RT-PCR. The results of RT-PCR were consistent with those of RNA sequencing. CONCLUSION: Expression of IL1RL1, IL33, SFRP4, and S1PR1 in the cumulus granulosa cells may be involved in the pathogenesis of diminished ovarian reserve.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis.

PURPOSE: This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection. METHODS: Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals. RESULTS: Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group. CONCLUSION: The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma.

p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.

Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma.

BACKGROUND: Cell division cycle 5-like (Cdc5L), as a pre-mRNA splicing factor, is a regulator of mitotic progression. Previous study found that deletion of endogenous Cdc5L decreases the cell viability via dramatic mitotic arrest, while the role of Cdc5L in cancer biology remains under debate. AIMS: To investigate the involvement of Cdc5L in the progression of hepatocellular carcinoma (HCC). METHODS: In this study, the expression of Cdc5L was evaluated by Western blot in 8 paired fresh HCC tissues and immunohistochemistry on 116 paraffin-embedded slices. We treated HCC cells by nocodazole to analyze the role of Cdc5L in mitotic progress. To determine whether Cdc5L could regulate the proliferation of HCC cells, we increased endogenous Cdc5L and analyzed the proliferation of HCC cells using Western blot, CCK8, flow cytometry assays, and colony formation analyses. Furthermore, Cdc5L-siRNA oligos were used to confirm that Cdc5L plays an essential role in HCC development. RESULTS: Cdc5L was highly expressed in HCC and significantly associated with multiple clinicopathological factors, including AJCC stage, tumor size, and Ki-67. Besides, univariate and multivariate survival analyses demonstrated that high Cdc5L expression was an independent prognostic factor for HCC patients' poor survival. Overexpression of Cdc5L favors cell cycle progress of HCC cells, while downregulation of Cdc5L results in cell cycle arrest at G2/M phase and reduced cell proliferation of HCC cells. CONCLUSIONS: Our findings suggested that Cdc5L could play an important role in the tumorigenesis of HCC and thus be a potential therapeutical target to prevent HCC progression.

Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma.

SYF2, also known as p29/NTC31/CBPIN, encodes a nuclear protein that interacts with Cyclin D-type binding-protein 1. SYF2 has been reported to be involved in pre-mRNA splicing and cell cycle regulation. In the present study, we observed that SYF2 was obviously upregulated in HCC tumor tissues and cell lines, and its level was positively correlated with the tumor grade and Ki-67 expression, as well as poor prognosis of HCC. In vitro, using serum starvation-refeeding experiment, our results suggested that SYF2 was upregulated in proliferating HCC cells, and was positive correlated with the expression of PCNA and Cyclin D1. In addition, depletion of SYF2 decreased PCNA and Cyclin D1 levels. Accordingly, interference of SYF2 resulted in cells cycle arrest at G1/S phase in Huh7 HCC cells. Furthermore, we found that SYF2 might interact with Cyclin D1 and could confer doxorubicin resistance in HCC cells. These findings revealed that SYF2 might play a regulatory role in the proliferation of HCC cells. In summary, SYF2 may be a novel prognostic marker and serve as a potential therapeutic target in HCC.

HES5 promotes cell proliferation and invasion through activation of STAT3 and predicts poor survival in hepatocellular carcinoma.

OBJECTIVES: HES5 is a member of the basic helix-loop-helix (bHLH) family of transcription factors, and involved in cell differentiation and proliferation in a variety of tissues other than HCC. Therefore, we have characterized HES5 and investigated its role during hepatocarcinogenesis. METHODS: We first examined the expression of HES5 in eight paired frozen HCC and adjacent noncancerous liver tissues by Western blot. Immunohistochemistry was performed to confirm our results in 58 HCC samples and evaluated the relativity between the expression of HES5 and clinicopathological variables and estimated the prognostic significance. Moreover, Western blot examined the expression of downstream proteins by siRNA HES5. Flow cytometer assay was performed to investigate the role of HES5 in the process of HCC. RESULTS: We found that HES5 was upregulated in HCC specimens. The data showed that high expression of HES5 was tightly associated with histological grade (P<0.01) and metastasis (P<0.01), and positively correlated with proliferation marker Ki-67 (P<0.01). Moreover, the results show that abnormal expression of HES5 influences cell growth and cell cycle of HCC cell lines. Furthermore, HES5 knockdown resulted in the reduction of p-STAT3. CONCLUSION: These results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.

Upregulated HOXC8 Expression Is Associated with Poor Prognosis and Oxaliplatin Resistance in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. It is indispensable to understanding molecular mechanisms of HCC progression and to developing clinically useful biomarkers for this disease. AIM: In this article, we examined whether HOXC8 was associated with the poor prognosis of hepatocellular carcinoma and explored the possible underlying mechanism. METHODS: The HOXC8 and Ki67 expression levels in 86 patients with hepatocellular carcinoma were examined using immunohistochemistry. HOXC8 levels in HCC cells were downregulated by siRNA transfection. The cycle progression and cell proliferation status of HCC cells and the oxaliplatin effectiveness were evaluated by flow cytometry and CCK-8 assay. HOXC8, CyclinD1, PCNA, Nkd2, and cleaved caspase-3 levels were detected by western blot. RESULTS: HOXC8 was upregulated in HCC tissues, compared with adjacent non-tumor ones. HOXC8 expression levels in 86 patients with hepatocellular carcinoma were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that HOXC8 was a significant predictor for overall survival of HCC patients. HOXC8 siRNA knockdown delayed the G1-S phase transition, inhibited cell proliferation, and attenuated resistance to oxaliplatin. CONCLUSIONS: HOXC8 promoted HCC proliferation and predicted poor prognosis. Furthermore, upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma.

Xuefu Zhuyu decoction alleviates deep vein thrombosis through inhibiting the activation of platelets and neutrophils via sirtuin 1/nuclear factor kappa-B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuefu Zhuyu Decoction (XZD), a renowned traditional Chinese medicine prescription, is widely employed for the management of conditions characterized by qi-stagnation and blood stasis. Although its anti-thrombotic effect on deep vein thrombosis (DVT) patients has been clinically observed, the underlying mechanism remains largely unexplored. AIM OF THE STUDY: Our aim was to investigate the mechanisms by which XZD exerted its effect on DVT. MATERIALS AND METHODS: The ultra performance liquid chromatography (UPLC) technique was employed to evaluate quality of XZD. To examine the effect of XZD on DVT, a DVT rat model with inferior vena cava (IVC) stenosis was established. The 4D-label-free proteomics approach was then utilized to uncover the possible mechanisms of XZD against DVT. Based on proteomics, citrullinated histone H3 (CitH3), along with serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) were observed the inhibitory activity of XZD on neutrophil activation. Subsequently, the marker of platelet activation, specifically glycoprotein IIb (CD41) and glycoprotein IIIa (CD61), were assessed along with the secretion of von Willebrand factor (vWF) to investigate the inhibitory activity of XZD on platelet activation. Finally, we explored the impact of XZD on the sirtuin 1 (SIRT1)/nuclear factor kappa-B (NF-κB) pathway, which was associated with the activation of platelets and neutrophils. RESULTS: Eight distinct components were identified for the quality control of XZD. XZD effectively reduced thrombus weight and length in DVT rats, without affecting the coagulation function or hematological parameters in the systemic circulation. Proteomics analysis revealed that XZD alleviated DVT by inhibiting the activation of platelets and neutrophils. The protein expression of CitH3, along with serum levels of TNF-α and IL-1ß, were reduced in XZD-treated DVT rats. Similarly, protein expressions of CD41 and CD61, along with the release of vWF, were markedly down-regulated in XZD-treated DVT rats. Finally, treatment with XZD resulted in an up-regulation of SIRT1 protein expression and a down-regulation of both acetylated NF-κB/p65 and phosphorylated NF-κB/p65 protein expressions in endothelium. CONCLUSIONS: XZD alleviates DVT by inhibiting the activation of platelets and neutrophils at the injured endothelium via the regulation of SIRT1/NF-κB pathway.

Multi-omics analysis of macrophage-associated receptor and ligand reveals a strong prognostic signature and subtypes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.

Supercritical fluid coating of flavonoids on excipients enhances drug release and antioxidant activity.

Supercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles. The results showed that temperature, pressure, carrier, and drug solution concentration have a large effect on yield. Within the study range, low supercritical CO2 density at higher temperature and lower pressure, a larger surface area carrier, and moderate drug solution concentration led to a higher yield. The effect of the solvent on the yield of flavonoids is a result of multiple factors. Scanning electron microscopy (SEM) images showed that the drug-loaded particles prepared from different carriers and solvents have different precipitations pattern on the carrier surface, and their particle sizes were smaller than unprocessed particles and those prepared by the SAS process. Fluorescence microscopy (FM) results showed that the flavonoids were uniformly coated on the carrier. X-ray powder diffraction (XRPD) results showed that the crystalline morphology of SAS-FB particles remained unchanged after the SAS-FB process, although the diffraction peak intensity decreased. The cumulative dissolution of SAS-FB particles was more than four times faster in the first 5 min than that of the unprocessed flavonoids. The antioxidant activity of SAS-FB processed LUT, NGR and DMY was 1.89-3.78 times, 4.92-10.68 times and 0.99-2.57 times higher than that of the untreated flavonoids, respectively. The approach provides a reference for the application of SAS-FB technology in flavonoids.

Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine.

The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0→∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.

Similar implantation competence in euploid blastocysts developed on day 5 or day 6 in young women: a retrospective cohort study.

The results from different studies are inconsistent regarding whether development potential correlated with embryo development speed after single euploid blastocyst transfer. The age-associated reproductive decline is not only because of the difference in aneuploidy rates but also because of metabolic and epigenetic changes of the embryos. Therefore, we aimed to assess the independent effect of embryo development speed on implantation potential in young women. A total of 326 young women who underwent preimplantation genetic testing for monogenic diseases with aneuploidy screening were analyzed. Day-5 and day-6 euploid blastocysts yielded similar implantation rates (65.20 vs. 61.22%). The odds ratio (OR) remained non-significant after adjusting for confounders (adjusted OR = 0.84, 95% confidence interval 0.52-1.36). There was a trend that day-6 euploid blastocysts had a higher miscarriage rate (13.33 vs. 9.20%). However, the live birth delivery rate of day-5 blastocysts was similar to that of day-6 blastocysts (59.20 vs. 53.06%). In the stratified analysis, live birth delivery rates were similar between day-5 and day-6 similarly graded euploid blastocysts (excellent and good, 62.04 vs. 64.71%; average, 58.73 vs. 53.70%; poor, 43.75 vs. 44.44%). Embryo development speed has no obvious impact on implantation competence in young women's vitrified/warmed euploid embryo transfer cycles.

Optimum synthesis of cactus-inspired SERS substrate with high roughness for paraquat detection.

Paraquat is a highly effective herbicide and widely used in agricultural production. However, paraquat residue is harmful for human health and can cause irreversible hazard. Thus, it is crucial for monitoring of paraquat residues. In this paper, an efficient SERS platform based on cactus-inspired nanoparticles is proposed for sensitive detection of paraquat. The cactus-liked nanoparticles obtained from one-pot stepwise reduction method possess multiple spiny structures and can produce abundant hot spots, resulting in remarkable SERS performance. SEM, TEM, UV-vis and Raman tests were conducted to characterize and optimize the morphology of cactus-liked nanoparticles under different preparation conditions. The synthesis mechanism and corresponding parameters influence mechanism of cactus-liked nanoparticles were explored in detail. Optimized substrate exhibited a high sensitivity with the detectable concentration of crystal violet (CV) down to 10-9 M and an excellent reproducibility proved by SERS mapping. Furthermore, it behaved good linear relationship with a correlation coefficient (R2) of 96.89% between Raman intensities and concentrations of paraquat, which indicates the SERS substrate prepared with cactus-liked nanoparticles could offer a great potential for identification of paraquat.

The Impact of Late Follicular Phase Progesterone Elevation on Cumulative Live Birth Rate and Embryo Quality in 4072 Freeze-All Cycles.

Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total of 4072 patients were reviewed. All patients used the freeze-all strategy. Multivariate regression analyses were used to assess the association of progesterone levels with both cumulative live birth and embryo quality. There was no significant difference in the cumulative live birth rate between the groups with progesterone level <1.5 ng/mL and ≥1.5 ng/mL. The progesterone level was not associated with cumulative live birth and embryo quality.

Optimum synthesis of Au@Ag nanoparticle as plasma amplifier to detect trace concentration of AFB1 via object-binder-metal SERS method.

The problem of aflatoxin contamination emerged gradually in the field of food safety. Surface-enhanced Raman spectroscopy (SERS) is an ultra-sensitive and non-destructive spectroscopy technology with extensive application prospects in the detection field. In this paper, with the detection of AFB1 as the target, Au@Ag NPs substrate with uniform morphology and strong SERS effect was prepared. Furthermore, the intermediates formed by hydrogen bonding between AFB1 and melamine facilitate the binding of toxin molecules to the substrate. Moreover, the AFB1-melamine-Au@Ag NPs detection system was established by optimizing the melamine dosage, and the limit of detection can reach 10-8 mol/L (M). In this method, AFB1 (concentration range of 10-4 M - 10-7 M) in tea oil, the Raman signal intensity of AFB1 shows an excellent linear, logarithmic relationship, and the correlation coefficient is 0.9685. Therefore, this work has achieved simple, sensitive, and stable AFB1 detection and has broad application potential in food safety detection.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

Characterization of excipients to improve pharmaceutical properties of sirolimus in the supercritical anti-solvent fluidized process.

Enhanced drug release and bioavailability of poorly soluble active pharmaceutical ingredient (API) can be achieved via a fluidized bed coating integrated with supercritical anti-solvent (SAS-FB) - a process of precipitating drug particles onto carrier granules. However, in the absence of excipients, SAS-FB often results in crystalline of the API on the surface of carriers, limiting the improvement of pharmaceutical properties. Co-processing with excipients is considered an effective approach to improve drug release in the SAS-FB process. Our study used sirolimus, an immune suppressive agent, as the model API to characterize excipients for their effect on pharmaceutical properties in the SAS-FB process. We show that co-precipitation of excipients and sirolumus impacts on carrier specific surface area and drug yield. Among the tested excipients, formulation containing polyvinylpyrrolidone K30 achieved the highest drug yield. Importantly, compared with Rapamune® tablet, our optimized formulation displayed a superior in vivo oral bioavailability by 3.05-fold in Sprague-Dawley rats and 3.99-fold in beagle dogs. A series of characterization of the processed API was performed to understand the mechanism by which excipients contributed to drug dissolution properties. Our study provides a useful guidance for the use of excipients in the SAS-FB technology to improve pharmaceutical properties of sirolimus and other poorly soluble drugs.

Oocyte Degeneration After ICSI Is Not an Indicator of Live Birth in Young Women.

Introduction: Intracytoplasmic sperm injection (ICSI) was introduced in 1990s as one of the most dramatic breakthroughs in assisted reproductive technology. Even with advances in ICSI technology, this mechanical micromanipulation carries a 5 to 19% risk of oocyte degeneration. Whether the presence of oocyte degeneration reflects the sibling oocyte quality and predicts the sibling embryo development potential and clinical pregnancy outcomes remains controversial. There is no study showing the competence of the sibling embryos from the prospective of cumulative live birth rate. Whether oocyte degeneration is associated with poor quality of the remainder of the cohort remains further to be elucidated. Method: This retrospective observational study included a total of 488 OPU cycles underwent ICSI with fresh cleavage stage embryo transfer and successive frozen/thawed embryo transfer (FET) cycles from January 2018 to December 2019. All female patients were under the age of 35 years, and underwent ICSI with or without oocyte degeneration (OD). Cycles with at least one oocyte degenerated were defined as oocyte degeneration group (OD group), and cycles with no oocyte degenerated were defined as non-OD group. The OD group was further divided to three subgroups according to different oocyte degeneration rate (<10%, 10-20%, and >20%). Results: There were no significant differences with regards to implantation rate (38.5% vs 35.1%, P=0.302), clinical pregnancy rate (54.9% vs 50.3%, P=0.340), and LBR per OPU cycle (47.0% vs 42.9%, P=0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD. The adjusted odds ratio of live birth rate per OPU cycle were similar in different oocyte degeneration rate subgroups. The ongoing pregnancy/LBR per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P=0.439). The cumulative LBR per OPU cycle was also comparable between OD and non-OD group (63.4% vs 64.8%, P=0.760). Conclusion: The results provide cycle-based evidence that the presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women.