Deubiquitylase ubiquitin-specific protease 7 plays a crucial role in the lineage differentiation of preimplantation blastocysts†.

Preimplantation embryos undergo a series of important biological events, including epigenetic reprogramming and lineage differentiation, and the key genes and specific mechanisms that regulate these events are critical to reproductive success. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase involved in the regulation of a variety of cellular functions, yet its precise function and mechanism in preimplantation embryonic development remain unknown. Our results showed that RNAi-mediated silencing of USP7 in mouse embryos or treatment with P5091, a small molecule inhibitor of USP7, significantly reduced blastocyst rate and blastocyst quality, and decreased total and trophectoderm cell numbers per blastocyst, as well as destroyed normal lineage differentiation. The results of single-cell RNA-seq, reverse transcription-quantitative polymerase chain reaction, western blot, and immunofluorescence staining indicated that interference with USP7 caused failure of the morula-to-blastocyst transition and was accompanied by abnormal expression of key genes (Cdx2, Oct4, Nanog, Sox2) for lineage differentiation, decreased transcript levels, increased global DNA methylation, elevated repressive histone marks (H3K27me3), and decreased active histone marks (H3K4me3 and H3K27ac). Notably, USP7 may regulate the transition from the morula to blastocyst by stabilizing the target protein YAP through the ubiquitin-proteasome pathway. In conclusion, our results suggest that USP7 may play a crucial role in preimplantation embryonic development by regulating lineage differentiation and key epigenetic modifications.

Sodium hyaluronate hydrogel for wound healing and human health monitoring based on deep eutectic solvent.

Hydrogel dressings traditionally promote wound healing by maintaining moisture and preventing infection rather than by actively stimulating the skin to regulate cell behavior. Electrical stimulation (ES) is known to modulate skin cell behavior and to promote wound healing. This study describes the first multifunctional conductive hydrogel for wound healing and health monitoring based on a deep eutectic solvent (DES). Sodium hyaluronate and polydopamine constituted the hydrogel skeleton, and tea tree oil and Panax notoginseng extract were used as the active ingredients to induce adhesion, promote antioxidant and antibacterial activity, and support biocompatibility of the hydrogel. The inclusion of DES increases the temperature resistance of the hydrogel and improves its environmental adaptability. We used a small, portable coin battery-powered to provide electrical stimulation. Treatment with both the hydrogel and ES resulted in a stronger therapeutic effect than that provided by the commercial DuoDERM dressing. The hydrogel detected movement and strain when applied as a sensor. Overall, this study reports the development of a multifunctional conductive hydrogel dressing based on DES as a wound healing and health monitor.

Zinc supplementation promotes oocyte maturation and subsequent embryonic development in sheep.

Zinc plays a crucial role in the growth and reproductive functions of animals. Despite the positive effects of zinc that have been reported in oocytes of cows, pigs, yaks, and other animals, the influence of zinc on sheep is little known. To investigate the effect of zinc on the in vitro maturation of sheep oocytes and subsequent parthenogenesis-activated embryonic development, we added different concentrations of zinc sulfate to the in vitro maturation (IVM) culture medium. The IVM culture medium with zinc improved the maturation of sheep oocytes and the subsequent blastocyst rate after parthenogenesis activation. Notably, it also enhanced the level of glutathione and mitochondrial activity while reducing levels of reactive oxygen species. Thus, zinc addition to the IVM medium improved the quality of oocytes with a positive effect on the subsequent development of oocytes and embryos.

Reproductive toxicity of microplastics in female mice and their offspring from induction of oxidative stress.

Microplastics (MPs) are an emerging pollutant that is becoming recognized as an increasingly serious environmental problem. The biological toxicity and resulting health risks of MPs have attracted much attention in the research community. While the effects of MPs on various mammalian organ systems have been described, their interactions with oocytes and the underlying mechanism of their activity within the reproductive system have remained ambiguous. Here, we discovered that oral administration of MPs to mice (40 mg/kg per day for 30 days) significantly reduced the oocyte maturation and fertilization rate, embryo development, and fertility. Ingestion of MPs significantly increased the ROS level in oocytes and embryos, leading to oxidative stress, mitochondrial dysfunction, and apoptosis. Moreover, mouse exposure to MPs caused DNA damage in oocytes, including spindle/chromosome morphology defects, and downregulation of actin and Juno expression in mouse oocytes. In addition, mice were also exposed to MPs (40 mg/kg per day) during gestation and lactation to determine trans-generational reproductive toxicity. The results showed that maternal exposure to MPs during pregnancy resulted in a decline in birth and postnatal body weight in offspring mice. Furthermore, MPs exposure of mothers markedly reduced oocyte maturation, fertilization rate, and embryonic development in their female offspring. This investigation provides new insights on the mechanism of MPs' reproductive toxicity and raises concerns for potential risks of MP pollution on the reproductive health of humans and animals.

[Principle and development of single base editing technology and its application in livestock breeding].

CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) is widely used in the field of livestock breeding. However, its low efficiency, untargeted cutting and low safety have greatly hampered its use for introducing single base mutations in livestock breeding. Single base editing, as a new gene editing tool, can directly replace bases without introducing double strand breaks. Single base editing shows high efficiency and strong specificity, and provides a simpler and more effective method for precise gene modification in livestock breeding. This paper introduces the principle and development of single base editing technology and its application in livestock breeding.

[Single base editing system mediates site-directed mutagenesis of genes GDF9 and FecB in Ouler Tibetan sheep].

In this study, a single base editing system was used to edit the FecB and GDF9 gene to achieve a targeted site mutation from A to G and from C to T in Ouler Tibetan sheep fibroblasts, and to test its editing efficiency. Firstly, we designed and synthesized sgRNA sequences targeting FecB and GDF9 genes of Ouler Tibetan sheep, followed by connection to epi-ABEmax and epi-BE4max plasmids to construct vectors and electrotransfer into Ouler Tibetan sheep fibroblasts. Finally, Sanger sequencing was performed to identify the target point mutation of FecB and GDF9 genes positive cells. T-A cloning was used to estimate the editing efficiency of the single base editing system. We obtained gRNA targeting FecB and GDF9 genes and constructed the vector aiming at mutating single base of FecB and GDF9 genes in Ouler Tibetan sheep. The editing efficiency for the target site of FecB gene was 39.13%, whereas the editing efficiency for the target sites (G260, G721 and G1184) of GDF9 gene were 10.52%, 26.67% and 8.00%, respectively. Achieving single base mutation in FecB and GDF9 genes may facilitate improving the reproduction traits of Ouler Tibetan sheep with multifetal lambs.

Iron-Based Nanocatalysts for Electrochemical Nitrate Reduction.

Nitrate has a high level of stability and persistence in water, endangering human health and aquatic ecosystems. Due to its high reliability and efficiency, the electrochemical nitrate reduction reaction (NO3 RR) is regarded as the best available option for mitigating excess nitrate in water and wastewater, especially for the removal of trace levels of nitrate. One of the most critical factors in the electrochemical reduction are the catalysts, which directly affect the reaction efficiency of nitrate removal. Iron-based nanocatalysts, which have the advantages of nontoxicity, wide availability, and low cost, have emerged as a promising electrochemical NO3 RR material in recent years. This review covers major aspects of iron-based nanocatalysts for electrochemical NO3 RR, including synthetic methods, structural design, performance enhancement, electrocatalytic nitrate reduction test, and reduction mechanism. The recent progress of iron-based nanocatalysts for electrochemical NO3 RR and the mechanism of functional advantages for modified structures are reviewed from the perspectives of loading, doping, and assembly strategies, in order to realize the conversion from pollutant nitrate to harmless nitrogen or ammonia and other sustainable products. Finally, challenges and future directions for the development of low-cost and highly-efficient iron-based nanocatalysts are explored.

Assembly: A Key Enabler for the Construction of Superior Silicon-Based Anodes.

Silicon (Si) is regarded as the most promising anode material for high-energy lithium-ion batteries (LIBs) due to its high theoretical capacity, and low working potential. However, the large volume variation during the continuous lithiation/delithiation processes easily leads to structural damage and serious side reactions. To overcome the resultant rapid specific capacity decay, the nanocrystallization and compound strategies are proposed to construct hierarchically assembled structures with different morphologies and functions, which develop novel energy storage devices at nano/micro scale. The introduction of assembly strategies in the preparation process of silicon-based materials can integrate the advantages of both nanoscale and microstructures, which significantly enhance the comprehensive performance of the prepared silicon-based assemblies. Unfortunately, the summary and understanding of assembly are still lacking. In this review, the understanding of assembly is deepened in terms of driving forces, methods, influencing factors and advantages. The recent research progress of silicon-based assembled anodes and the mechanism of the functional advantages for assembled structures are reviewed from the aspects of spatial confinement, layered construction, fasciculate structure assembly, superparticles, and interconnected assembly strategies. Various feasible strategies for structural assembly and performance improvement are pointed out. Finally, the challenges and integrated improvement strategies for assembled silicon-based anodes are summarized.

Effect of inoculation with newly isolated thermotolerant ammonia-oxidizing bacteria on nitrogen conversion and microbial community during cattle manure composting.

Nitrogen loss during composting is closely related to NH4+-N conversion, and ammonia-oxidizing bacteria (AOB) are important microorganisms that promote NH4+-N conversion. Since the biological activity of conventional AOB agents used for compost inoculation declines rapidly during the thermophilic phase of composting, new compound inoculants should be developed that are active during that phase. In the current study, the effects of inoculating cattle manure compost with newly isolated AOB (5%, v/w) [thermotolerant AOB X-2 strain (T-AOB-2), mesophilic AOB X-4 strain (M-AOB-4), and AOB X-2 combined with AOB X-4 (MT-AOB-2-4)] on the conversion of nitrogen, compost maturity, and the resident microbial community were studied. During 35 days of composting, compared with the control, AOB inoculation reduced NH3 emissions by 29.98-46.94%, accelerated the conversion of NH4+-N to NO2--N, increased seed germination values by 13.00-25.90%, and increased the abundance of the microbial community at the thermophilic phase (16.38-68.81%). Network analysis revealed that Bacillaceae play a crucial role in the composting process, with the correlation coefficients: 0.83 (p < 0.05) with NH3, 0.64 (p < 0.05) with NH4+-N, and 0.81 (p < 0.05) with NO2--N. In addition, inoculation with MT-AOB-2-4 notably increased the total nitrogen content of compost, prolonged the sanitation stage, and promoted compost maturity. Hence, MT-AOB-2-4 may be used to increase the microbial community abundance and improve the efficiency of cattle manure composting.

CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos.

Chromatin assembly factor-1, subunit b (CHAF1b), the p60 subunit of the chromatin-assembly factor-1 (CAF-1) complex, is an evolutionarily conserved protein that has been implicated in various biological processes. Although a variety of functions have been attributed to CHAF1b, its function in preimplantation embryos remains obscure. In this study, we showed that CHAF1b knockdown did not affect the blastocyst rate, but resulted in a low blastocyst hatching rate, outgrowth failure in vitro, and embryonic lethality after implantation in vivo. Notably, CHAF1b depletion increased apoptosis and caused down-regulated expression of key regulators of cell fate specification, including Oct4, Cdx2, Sox2, and Nanog. Further analysis revealed that CHAF1b mediated the replacement of H3.3 with H3.1/3.2, which was associated with decreased repressive histone marks (H3K9me2/3 and H3K27me2/3) and increased active histone marks (H3K4me2/3). Moreover, RNA-sequencing analysis revealed that CHAF1b depletion resulted in the differential expression of 1508 genes, including epigenetic modifications genes, multiple lineage-specific genes, and several genes encoding apoptosis proteins. In addition, assay for transposase-accessible chromatin-sequencing analysis demonstrated that silencing CHAF1b altered the chromatin accessibility of lineage-specific genes and epigenetic modifications genes. Taken together, these data imply that CHAF1b plays significant roles in preimplantation embryos, probably by regulating epigenetic modifications and lineage specification.

Oral isoniazid causes oxidative stress, oocyte deterioration and infertility in mice.

Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.

SUMO2, a small ubiquitin-like modifier, is essential for development of murine preimplantation embryos.

Small ubiquitin-like modifier 2 (SUMO2) is a small protein that modulates the stability and activity of other proteins. Although a variety of activities have been attributed to SUMO2, its function in preimplantation embryos is still obscure. We first explored the expression of SUMO2 protein in early embryos, and showed that compared with the 2-cell stage, the expression was increased at first, peaked at the 8-cell stage, and then dramatically decreased. To study the function of SUMO2, we used siRNA microinjection to knock down SUMO2.The silencing of SUMO2 significantly reduced the rate of in vitro blastocyst development from 75.56% to 40.60%. Notably, knockdown of SUMO2 (KD) altered the expression of CDX2, OCT4, and NANOG. The number of cells expressing CDX2 decreased, while OCT4 and NANOG were ectopically expressed in siSUMO2 embryos. The global H3K27me3 levels in SUMO2-KD embryos also were lower than in untreated embryos. Taken together, SUMO2 appears to play a significant role in mouse preimplantation embryos probably through key epigenetic modifications and regulation of pluripotency genes.

Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice.

Lead, a common metallic contaminant, is widespread in the living environment, and has deleterious effects on the reproductive systems of humans and animals. Although numerous toxic effects of lead have been reported, the effects and underlying mechanisms of the impacts of lead exposure on the female reproductive system, especially oocyte maturation and fertility, remain unknown. In this study, mice were treated by gavage for seven days to evaluate the reproductive damage and role of Nrf2-mediated defense responses during lead exposure. Lead exposure significantly reduced the maturation and fertilization of oocytes in vivo. Additionally, lead exposure triggered oxidative stress with a decreased glutathione level, increased amount of reactive oxygen species, and abnormal mitochondrial distribution. Moreover, lead exposure caused histopathological and ultrastructural changes in oocytes and ovaries, along with decreases in the activities of catalase, glutathione peroxidase, total superoxide dismutase, and glutathione-S transferase, and increases in the levels of malonaldehyde in mouse ovaries. Further experiments demonstrated that lead exposure activated the Nrf2 signaling pathway to protect oocytes against oxidative stress by enhancing the transcription levels of antioxidant enzymes. In conclusion, our study demonstrates that lead activates the Nrf2/Keap1 pathway and impairs oocyte maturation and fertilization by inducing oxidative stress, leading to a decrease in the fertility of female mice.

Outcomes for Hyperthermia Combined with Concurrent Radiochemotherapy for Patients with Cervical Cancer.

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

LncRNA miR143HG Up-Regulates p53 In Endometrial Carcinoma By Sponging miR-125a.

INTRODUCTION: MiR143HG is a recently identified tumor suppressor in bladder cancer. We performed bioinformatics prediction and found that miR143HG can form base pairs with miR-125a. This study was therefore carried out to explore the interaction between miR143HG and miR-125a in endometrial carcinoma (EC). METHODS: Gene expression was analyzed by qPCR and Western blot. Interactions among genes were analyzed by over-expression experiments. Cell apoptosis after transfections was analyzed by cell apoptosis assay. RESULTS: We found that the down-regulation of miR143HG in EC predicted poor survival. Bioinformatics analysis showed that miR-125a could bind miR143HG. In EC tissues, miR143HG was positively correlated with p53, not miR-125a. In EC cells, miR143HG and miR-125a over-expression failed to affect the expression of each other. However, miR143HG over-expression led to the up-regulated p53. MiR-125a over-expression played the opposite role and attenuated the effects of miR143HG over-expression. Cell apoptosis analysis showed that miR143HG and p53 over-expression led to an increased cell apoptotic rate. MiR-125a over-expression played the opposite role and attenuated the effects of miR143HG over-expression. CONCLUSION: MiR143HG may up-regulate p53 in EC by sponging miR-125a to promote cancer cell apoptosis.

Alantolactone enhances gemcitabine sensitivity of lung cancer cells through the reactive oxygen species-mediated endoplasmic reticulum stress and Akt/GSK3ß pathway.

Lung cancer is one of the leading causes of cancer­associated mortality in China and globally. Gemcitabine (GEM), as a first­line therapeutic drug, has been used to treat lung cancer, but GEM resistance poses a major limitation on the efficacy of GEM chemotherapy. Alantolactone (ALT), a sesquiterpene lactone compound isolated from Inula helenium, has been identified to exert anticancer activity in various types of cancer, including breast, pancreatic, lung squamous and colorectal cancer. However, the underlying mechanisms of the anticancer activity of ALT in lung cancer remain to be fully elucidated. The present study aimed to determine whether ALT enhances the anticancer efficacy of GEM in lung cancer cells and investigated the underlying mechanisms. The cell viability was assessed with a Cell Counting Kit­8 assay. The cell cycle, apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression of cell cycle­associated and apoptosis­associated proteins were determined by western blot analysis. The results demonstrated that ALT inhibited cell growth and induced S­phase arrest and cell apoptosis in A549 and NCI­H520 cells. Furthermore, ALT increased the level of ROS, inhibited the Akt/glycogen synthase kinase (GSK)3ß pathway and induced endoplasmic reticulum (ER) stress in A549 and NCI­H520 cells. Additionally, ALT treatment sensitized lung cancer cells to GEM. Analysis of the molecular mechanisms further revealed that ALT enhanced the anticancer effects of GEM via ROS­mediated activation of the Akt/GSK3ß and ER stress pathways. In conclusion, combined treatment with ALT and GEM may have potential as a clinical strategy for lung cancer treatment.

Relationship of Physical Education Curriculum Implementation and Mathematics Achievement in Chinese Youth.

PURPOSE: Previous studies indicated a positive association between physical education (PE) and mathematics achievement (MA). This study explored how PE curriculum implementation relates to MA using data from the China National Assessment of Education Quality (CNAEQ) in 2015, including Mathematics (CNAEQ-MA 2015) as well as Physical Education & Health (CNAEQ-PEH 2015). METHOD: This study included 22,619 students (48.7% girls) age 13.96 ± 0.64 yr. from the national sample of Grade 8 students from CNAEQ. During 2015, MA and cardiorespiratory fitness (CF) were assessed. PE curriculum implementation, personal hygiene, eating habits, PE interest, mathematics interest, and self-confidence were collected via a self-report student survey. Personal hygiene and eating habits were combined to create the latent variable, healthy lifestyle (HL). Structural equation modeling was applied to examine the associations. Socioeconomic status, school location, Body Mass Index (BMI), and sex were all controlled. RESULTS: PE curriculum implementation had an indirect, positive association with MA through CF, HL-mathematics interest, and HL-mathematics self-confidence. Together, the model explained 27.8% of the variance in MA. CONCLUSION: PE curriculum implementation may benefit mathematics education, and this link is mainly through HL, CF, mathematics interest, and self-confidence.

Pristimerin enhances the effect of cisplatin by inhibiting the miR­23a/Akt/GSK3ß signaling pathway and suppressing autophagy in lung cancer cells.

Lung cancer is a common type of cancer with a high mortality rate in China. Cisplatin (Cis) is one of the most effective broad­spectrum chemotherapeutic drugs for the treatment of advanced lung cancer. However, Cis resistance remains an obstacle in the treatment of advanced lung cancer. Pristimerin (Pris), a naturally occurring triterpenoid quinone compound, not only possesses anticancer properties, but also enhances chemosensitivity. Therefore, the present study aimed to investigate whether Pris can enhance the chemosensitivity of lung cancer cells to Cis and identify the underlying mechanism. A Cell Counting kit­8 and flow cytometry were used to determine cell viability, cell cycle progression and apoptosis in A549 and NCI­H446 cells. Western blotting was used to determine cell apoptosis­related, cell cycle­related and autophagy­related proteins. The results showed that Pris inhibited cell proliferation, and induced G0/G1 arrest and cell apoptosis in A549 and NCI­H446 cells. The western blotting revealed that Pris effectively synergized with Cis to induce cell apoptosis by inhibiting the microRNA­23a/Akt/glycogen synthase kinase 3ß signaling pathway and suppressing autophagy. In vivo xenograft experiments confirmed that Pris effectively synergized with Cis to suppress tumor growth. Collectively, these results indicate that Pris synergized with Cis and that this may be a potential therapeutic strategy to overcome lung cancer.

Retracted Article: RNA-sequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR.

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues. Five miRNAs were sharply downregulated in the cancer tissue, including miR-199a, miR-22, miR-615, miR-3681-3p (miR-3681), and miR-1193. Among them, miR-3681 was uncharacterized. The results from qPCR analysis showed that miR-3681 expression was decreased in patients with cervical cancer compared with the control, and decreased in the human cervical cancer cell lines SiHa, HeLa, C4-1, C-33A and Caski, compared with the normal human cervical epithelial cell line HCerEpic. Then, different concentrations of miR-3681 mimic and miR-3681 inhibitor were respectively transfected into the human cervical cancer cell line C-33A, and the expression of miR-3681, cell proliferation, cell apoptosis and cell migration were measured after 48 h. The results showed that the miR-3681 mimic increased the miR-3681 level, suppressed cell proliferation and migration, and induced cell apoptosis in a dose-dependent manner. In contrast, the miR-3681 inhibitor decreased the miR-3681 level, promoted cell proliferation and migration, and inhibited cell apoptosis in a dose-dependent manner. Moreover, bioinformatics analysis showed that there was a miR-3681 binding site in the mRNA 3'UTR of HGFR, which was robustly upregulated in cervical cancer cell lines compared with HCerEpic cells. In addition, luciferase activity analysis demonstrated that miR-3681 could directly target HGFR, which promoted the proliferation and migration of C-33A cells via activation of the PI3K/Akt pathway in a dose-dependent manner. Furthermore, our results showed that knockdown of HGFR could antagonize the promotion of anti-miR-3681 on the activation of the PI3K/Akt pathway and cell proliferation and migration. In conclusion, MiR-3681 was identified as a negative regulator in the proliferation and migration of cervical cancer cells. This function is associated with the posttranscriptional suppression of HGFR and the deactivation of the PI3K/Akt pathway.

Upregulated delta-like protein 3 expression is a diagnostic and prognostic marker in endometrial cancer: A retrospective study.

Upregulated delta-like protein 3 (DLL3) functions as a Notch ligand and has been a target for cancer therapy. The present study assessed DLL3 expression as a tumor marker for endometrial cancer.RNA-Seq expression data and clinicopathologic records from 545 patients with endometrial cancer were downloaded from The Cancer Genome Atlas database. Mann-Whitney U and logistic regression tests were applied to associate the level of DLL3 expression with clinical variables from the patients. Kaplan-Meier curves and log-rank tests were performed to compare overall survival of patients stratified by different levels of DLL3 expression. Multivariate Cox regression tests were used to analyze independent predictors for endometrial cancer. DLL3 expression was upregulated in endometrial cancer tissues compared to para-carcinoma tissues (P = .0003). High DLL3 expression was associated with the age of patients (odds ratio [OR] = 1.74), advanced stages of the International Federation of Gynecology and Obstetrics system (OR = 2.9), grade III/IV (OR = 5.1), myometrial invasion (OR = 2.2), pelvic involvement (OR = 12.9), and para-aortic lymph node metastasis (OR = 9.9) (all P ≤ .001). Furthermore, upregulated DLL3 expression was also associated with a median overall survival of 112 months (HR = 1.85, confidence internal 1.202-2.846, P = .005). The multivariate analysis showed that DLL3 overexpression and advanced tumor stages, grades, and lymph node metastases were all independent prognostic predictors for endometrial cancer.The DLL3 expression could be a potential and novel tumor marker for early diagnosis and an independent predictor of poor survival for patients with endometrial cancer.