TRIM21 promotes tumor progression and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: The ubiquitin ligase family member triplex motif protein 21 (TRIM21), which is involved in the proliferation, metastasis, and selective death of tumor cells, is crucial in the ubiquitination of a number of tumor marker proteins. As research progresses, more studies demonstrate that TRIM21 expression levels can be used to predict cancer prognosis. However, it is unclear how exactly TRIM21 contributes to cervical squamous carcinoma. METHODS: Immunohistochemistry, Western Blot, and q-PCR were utilized to determine the expression level of TRIM21 in 113 patients with CESC removed by stage I surgery at Xijing Hospital from 2018 to 2023 using paraffin-embedded tumor tissues and 12 pairs of fresh tumor tissues and their paracancerous tissues. Log-rank analysis using SPSS 23.0 was performed for prognosis and survival analysis using univariate/multifactorial analysis. CCK-8, wound-healing and Scratch assay verified that TRIM21 promoted cell proliferation, migration and invasion. The effect of overexpression and knockdown of TRIM21 on tumor stemness was examined using sphere-forming assay and Western Blot. Finally, we constructed a xenograft model to observe the effect of TRIM21 on tumorigenesis in Si Ha cell lines in vivo. RESULTS: TRIM21 expression is greater in CESC tissues than in paracancerous tissues, according to immunohistochemical data. Similarly, at the protein and mRNA levels, we verified this conclusion using Western-Blotting and q-PCR. Prognostic and OS analysis showed that TRIM21 expression levels are associated with individual prognostic factors. CCK-8, Wound healing, Transwell, and Sphere-forming tests all demonstrated that TRIM21 overexpression enhances Ca Ski cell proliferation, migration, invasion, and stemness. TRIM21 knockdown in Si Ha inhibited tumor cell proliferation, migration, invasion, and stemness. The experimental results of xenograft models demonstrated that TRIM21 knockdown in Si Ha cells inhibited tumor development. CONCLUSION: TRIM21 is a poor predictor of prognosis for cervical squamous cell carcinoma and might open up new avenues for investigation into therapeutic targets.

Ovarian stimulation protocols for poor ovarian responders: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of manifold ovarian stimulation protocols for patients with poor ovarian response. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched until February 14, 2021. Primary outcomes included clinical pregnancy rate per initiating cycle and low risk of cycle cancellation. Secondary outcomes included number of oocytes retrieved, number of metaphase II (MII) oocytes, number of embryos obtained, number of transferred embryos, endometrial thickness on triggering day and estradiol (E2) level on triggering day. The network plot, league table, rank probabilities and forest plot of each outcome measure were drawn. Therapeutic effects were displayed as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: This network meta-analysis included 15 trials on 2173 participants with poor ovarian response. Delayed start GnRH antagonist was the best regimen in terms of clinical pregnancy rate per initiating cycle (74.04% probability of being the optimal), low risk of cycle cancellation (75.30%), number of oocytes retrieved (68.67%), number of metaphase II (MII) oocytes (97.98%) and endometrial thickness on triggering day (81.97%), while for E2 level on triggering day, microdose GnRH agonist (99.25%) was the most preferred. Regarding number of embryos obtained and number of transferred embryos, no statistical significances were found between different ovarian stimulation protocols. CONCLUSION: Delayed start GnRH antagonist and microdose GnRH agonist were the two superior regimens in the treatment of poor ovarian response, providing favorable clinical outcomes. Future investigation is needed to confirm and enrich our findings.

Assisted reproductive technology causes reduced expression of amino acid transporters in human full-term placentas.

OBJECTIVE: In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of amino acid transporters in placentas during mid-to late-gestation. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. METHODS: We choose the placenta tissue of pregnant woman by ART in term birth (ART group) and by natural pregnancy in term birth (control group) to compare the birth weight of the baby, placental weight and ratio of the fetal/placental weight of these two groups. We then detect the mRNA and protein expression of placental amino acid transporter genes (SNAT1, SNAT2, SNAT4, LAT1 and LAT2) in these two groups by real-time quantitative PCR, Western blot and immunofluorescence staining. Additionally, the PI3K-AKT-mTOR signaling activity was also analyzed. RESULTS: There were no statistical differences in new birth weight between the ART group and the control group. Compared with the control group, the placenta weight of baby was significantly higher in ART group and ratio of the fetal/placental weight was significantly lower in ART group. We found that the mRNA and protein expression of A system of amino acid transporter SNAT1, SNAT2 and SNAT4 in placenta were significantly down-regulated in ART group compared with placentas from natural pregnancies. Additionally, there were no statistical differences of the mRNA and protein expression of L system of amino acid transporter LAT1 between these two groups, but amino acid transporter LAT2 in placenta was significantly down-regulated in ART group. Furthermore, the PI3K-AKT-mTOR signaling activity was inhibited in ART group. CONCLUSIONS: ART leads to the expressions of amino acid transporter genes SNAT1, SNAT2, SNAT4 and LAT2 significantly down-regulated in placenta accompanied by the PI3K-AKT-mTOR signaling inhibition, which suggests that ART may affect the function of placenta amino acid transporter during the late pregnancy, leading to enlarged placentas and probably low birth weight.

Epigallocatechin-3-gallate (EGCG) attenuates inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced endometritis via silent information regulator transcript-1 (SIRT1)/nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) pathway.

The protective effects of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl-2, cleaved caspase-3, silent information regulator transcript-1 (SIRT1), nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase1 was detected by Western blot and real-time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS-induced uterine histopathological changes, MPO activity, pro-inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.

Tricyclic Aza-Andrographolide Derivatives from Late-Stage Hydroamination and Their Anti-human Coronavirus (Anti-HCoV) Activity.

A late-stage functionalization (LSF) of the natural product andrographolide for the efficient assembly of a range of structurally interesting and diverse tricyclic-aza derivatives was developed. The key to the diversification is a photo-catalyzed intramolecular hydroamination reaction, and acridinium derivatives were demonstrated to be the optimal catalysts. Additionally, the synthesized tricyclic aza-andrographolide derivatives were found to inhibit human coronavirus with high potency.

Combining visible-light induction and copper catalysis for chemo-selective nitrene transfer for late-stage amination of natural products.

Nitrene transfer chemistry is an effective strategy for introducing C-N bonds, which are ubiquitous in pharmaceuticals, agrochemicals and diverse bioactive natural products. The development of chemical methodology that can functionalize unique sites within natural products through nitrene transfer remains a challenge in the field. Herein, we developed copper catalyzed chemoselective allylic C-H amination and catalyst-free visible-light induced aziridination of alkenes through nitrene transfer. In general, both reactions tolerate a wide range of functional groups and occur with predictable regioselectivity. Furthermore, combination of these two methods enable the intermolecular chemo-selective late-stage amination of biologically active natural products, leading to C-H amination or C=C aziridination products in a tunable way. A series of control experiments indicate two-step radical processes were involved in both reaction systems.

Clinical pregnancy outcomes prediction in vitro fertilization women based on random forest prediction model: A nested case-control study.

The present study aimed to analyze the risk factors influencing the in vitro fertilization embryo transfer (IVF-ET) pregnancy and to construct a prediction model for clinical pregnancy outcome in patients receiving IVF-ET based on the predictors. In this nested case-control study, the data of 369 women receiving IVF-ET were enrolled. Univariate and multivariate Logistic regression analyses were conducted to identify the potential predictors. Ten-fold cross validation method was used to validate the random forest model for predicting the clinical pregnancy. The receiver operating characteristic curve was drawn to evaluate the prediction ability of the model. The importance of variables was shown according to Mean Decrease Gini. The data delineated that age (odds ratio [OR]= 1.093, 95% confidence interval [CI]: 1.036-1.156, P = .0010), body mass index (BMI) (OR = 1.094, 95%CI: 1.021-1.176, P = .012), 3 cycles (OR = 0.144, 95%CI: 0.028-0.534, P = .008), hematocrit (HCT) (OR = 0.865, 95% CI: 0.791-0.943, P = .001), luteinizing hormone (LH) (OR = 0.678, 95%CI: 0.549-0.823, P < .001), progesterone (P) (OR = 2.126, 95%CI: 1.112-4.141, P = .024), endometrial thickness (OR = 0.132, 95%CI: 0.034-0.496, P = .003) and FSH (OR = 1.151, 95%CI: 1.043-1.275, P = .006) were predictors associated with the clinical pregnancy outcome of patients receiving IVF-ET. The results might provide a novel method to identify patients receiving IVF-ET with a high risk of poor pregnancy outcomes and provide interventions in those patients to prevent the occurrence of poor pregnancy outcomes.

Effect of Initial Microstructure on the Toughness of Coarse-Grained Heat-Affected Zone in a Microalloyed Steel.

Toughness of the coarse-grained-heat-affected-zone (CGHAZ) strongly depends on the prior austenite grain size. The prior austenite grain size is affected not only by chemical composition, thermal cycle, and dissolution of second-phase particles, but also by the initial microstructure. The effect of base metal microstructure (ferrite/pearlite obtained by air cooling and martensite obtained by water-quenching) on Charpy impact toughness of the CGHAZ has been investigated for different heat inputs for high-heat input welding of a microalloyed steel. A welding thermal cycle with a heat input of 100 kJ/cm and 400 kJ/cm were simulated on the MMS-300 system. Despite a similar microstructure in the CGHAZ of both the base metals, the average Charpy impact energy for the air-cooled base metal was found to be higher than the water-quenched base metal. Through thermo-kinetic simulations, it was found that a higher enrichment of Mn/C at the ferrite/austenite transformation interface of the CGHAZ of water-quenched base metal resulted in stabilizing austenite at a lower A1 temperature, which resulted in a coarser austenite grain size and eventually lowering the toughness of the CGHAZ.

[XPS analysis of beads formed by fuse breaking of electric copper wire].

The in-depth composition of beads formed by fuse breaking of the electric copper wire in different circumstances was studied by XPS with Ar+ ion sputtering. In addition, the measured Auger spectra and the calculated Auger parameters were compared for differentiation of the substances of Cu and Cu2O. Corresponding to the sputtering depth, the molten product on a bead induced directly by fuse breaking of the copper wire without cover may be distinguished as three portions: surface layer with a drastic decrease in carbon content; intermediate layer with a gentle change in oxygen content and gradually diminished carbon peak, and consisting of Cu2O; transition layer without Cu2O and with a rapid decrease in oxygen content. While the molten product on a bead formed by fuse breaking of the copper wire after its insulating cover had been burned out may be distinguished as two portions: surface layer with carbon content decreasing quickly; subsurface layer without Cu2O and with carbon and oxygen content decreasing gradually. Thus, it can be seen that there was an obvious interface between the layered surface product and the substrate for the first type of bead, while as to the second type of bead there was no interface. As a result, the presence of Cu2O and the quantitative results can be used to identify the molten product on a bead induced directly by fuse breaking of the copper wire without cover and the molten product on a bead formed by fuse breaking of the cupper wire after its insulating cover had been burned out, as a complementary technique for the judgments of fire cause.