METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

Multi-objective and multi-solution source mask optimization using NSGA-II for more direct process window enhancement.

Source and mask optimization (SMO) technology is increasingly relied upon for resolution enhancement of photolithography as critical dimension (CD) shrinks. In advanced CD technology nodes, little process variation can impose a huge impact on the fidelity of lithography. However, traditional source and mask optimization (SMO) methods only evaluate the imaging quality in the focal plane, neglecting the process window (PW) that reflects the robustness of the lithography process. PW includes depth of focus (DOF) and exposure latitude (EL), which are computationally intensive and unfriendly to gradient-based SMO algorithms. In this study, we propose what we believe to be a novel process window enhancement SMO method based on the Nondominated Sorting Genetic Algorithm II (NSGA-II), which is a multi-objective optimization algorithm that can provide multiple solutions. By employing the variational lithography model (VLIM), a fast focus-variation aerial image model, our method, NSGA-SMO, can directly optimize the PW performance and improve the robustness of SMO results while maintaining the in-focus image quality. Referring to the simulations of two typical patterns, NSGA-SMO showcases an improvement of more than 20% in terms of DOF and EL compared to conventional multi-objective SMO, and even four times superior to single-objective SMO for complicated patterns.

Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway.

BACKGROUND: Pyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI. METHODS AND RESULTS: The expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1ß production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis. CONCLUSION: Our results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer.

RESEARCH QUESTION: Do patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DESIGN: A retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1-4) for further analysis. RESULTS: The rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks' gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11-2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30-3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09-3.68). CONCLUSIONS: Chronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

Oxygen evolution reaction (OER) active sites in BiVO4 studied using density functional theory and XPS experiments.

Bismuth vanadate (BiVO4/BVO) has been widely studied as a photocatalytic water splitting semiconductor material in recent years because of its many advantages, such as its ease of synthesis and suitable band gap (2.4 eV). However, BVO still has some disadvantages, one of which is the low photocatalytic water oxidation activity. It is intriguing and unexpected to note that in the current literature, Bi atoms are taken as the oxygen evolution reaction (OER) active sites, while V metal atoms are not investigated in the OER, and the underlying reason for this remains unknown. In this work, using density functional theory (DFT) calculations and ab initio molecular dynamics simulations, we found that in BVO, the VO4 tetrahedron structure is very stable and there is strong surface reconstruction that leads to the V atoms on the surface having the same coordinates as in the bulk. For some high index surfaces, there are some theoretically predicted unsaturated V sites, but it is very easy to form a VO4 tetrahedron structure again by taking oxygen atoms from water. The other intermediates of OER are difficult to adsorb or desorb on this VO4 structure, which makes the V sites in BVO unsuitable as OER active sites. This VO4 structure remained stable during the molecular dynamics simulation at 300 and 673 K. The XPS characterization of various BVO morphologies validates our primary findings from DFT and molecular dynamics simulations. It reveals the presence of unsaturated Bi sites on the BVO surface, while unsaturated V sites are not observed. This study provides novel insights into the enhancement of OER activity of BVO and offers a fundamental understanding of OER activity in other photocatalysts containing V atoms.

Comparison of the Watson formula and bioimpedance spectroscopy for measuring body volume and calculating kt/V in patients with peritoneal dialysis.

CONCLUSION: There were significant differences between Vwat and Vbis and between Kt/Vwat and Kt/Vbis. Kt/Vwat may underestimate small-solute dialysis adequacy in most cases. Kt/Vbis instead of Kt/Vwat could be accounted for in creating individualized dialysis prescriptions if the patient has no obvious clinical symptoms.

Knockdown of AK142426 suppresses M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun.

BACKGROUND: Peritoneal fibrosis is a common complication of peritoneal dialysis, which may lead to ultrafiltration failure and ultimately treatment discontinuation. LncRNAs participate in many biological processes during tumorigenesis. We investigated the role of AK142426 in peritoneal fibrosis. METHODS: The AK142426 level in peritoneal dialysis (PD) fluid was detected by quantitative real-time-PCR assay. The M2 macrophage distribution was determined by flow cytometry. The inflammatory cytokines of TNF-α and TGF-ß1 were measured by ELISA assay. The direct interaction between AK142426 and c-Jun was evaluated by RNA pull-down assay. In addition, the c-Jun and fibrosis related proteins were assessed by western blot analysis. RESULTS: The PD-induced peritoneal fibrosis mouse model was successfully established. More importantly, PD treatment induced M2 macrophage polarization and the inflammation in PD fluid, which might be associated with exosome transmission. Fortunately, AK142426 was observed to be upregulated in PD fluid. Mechanically, knockdown of AK142426 suppressed M2 macrophage polarization and inflammation. Furthermore, AK142426 could upregulate c-Jun through binding c-Jun protein. In rescue experiments, overexpression of c-Jun could partially abolish the inhibitory effect of sh-AK142426 on the activation of M2 macrophages and inflammation. Consistently, knockdown of AK142426 alleviated peritoneal fibrosis in vivo. CONCLUSIONS: This study demonstrated that knockdown of AK142426 suppressed M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun, suggesting that AK142426 might be a promising therapeutic target for patients of peritoneal fibrosis.

The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Introduction: The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. Material and methods: C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Results: Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). Conclusions: The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.

Theoretical insight into the anion vacancy healing process during the oxygen evolution reaction on TaON and Ta3N5.

Anion vacancies are common defects in materials, and they are usually much more stable on the outermost surface. These vacancies are sometimes taken as active sites in some reactions during catalysis. During the oxygen evolution reaction (OER), these vacancies may be healed by oxygen atoms from water. But this healing process is not well understood yet. In this work, we investigated the details of the anion vacancy healing process in the OER using TaON and Ta3N5 as models. In the OER process, we found that the vacancies are stable and cannot be healed without an applied potential. But with the equilibrium potential of 1.23 V, the vacancies on the outermost top surface will be healed. The oxygen vacancies, after healing, revert back to a clean surface. The nitrogen vacancies become an oxygen doped surface after vacancy healing. We also investigated the vacancy healing process on other well-known photocatalysts, like TiO2, BiVO4, WO3, α-Fe2O3, NaTaO3 and SrTiO3, and we found that the vacancies on the top surface of these materials will also be healed in the OER with an applied equilibrium potential of 1.23 V. The results presented here could expand to other materials used for the OER in (photo) electro-catalysis and photocatalysis. This work provides a new insight for understanding the role of vacancies in the OER.

Polaron formation and transport in Bi2WO6 studied by DFT+U and hybrid PBE0 functional approaches.

Bi2WO6 (BWO) is considered as a promising material for photocatalytic water splitting. Its unique layered structure leads the charge separation, and transport is different from other materials. However, the charge transport mechanisms in BWO are not well understood. In this work, we investigated polaron formation and transport in BWO using the DFT+U and hybrid PBE0 functional approaches. We found that the electron will form 2-dimensional (2D)-shaped polarons among W sites in the ab plane of BWO with approximately 55% polaron density state on the central W site. This type of polaron is similar to the electron polarons in WO3. For other W-based materials, the electrons may also form a 2D-shaped polaron. We found that the W 6s orbital plays an important role in these 2D-shaped electron polarons. The calculated mobility of electron polarons in BWO was consistent with experimental findings. For the hole state, it could form a small hole polaron on the O site with O 2p in character. However, it will not form a polaron on the Bi site, which is quite different from BiVO4. This study provides insight for understanding polaron formation and transport in materials with W and Bi ions. It also provides understanding regarding charge separation and transport for materials with layered structures.

Role of IGF-1R in epithelial-mesenchymal transdifferentiation of human peritoneal mesothelial cells.

BACKGROUND: Peritoneal fibrosis (PF) is caused by epithelial-mesenchymal transdifferentiation (EMT) in the peritoneum under high glucose (HG) conditions. The study aimed to explored the role of Insulin-like growth factor 1 receptor (IGF-1R) in the regulation of EMT in human peritoneal mesothelial cells (HPMCs). METHODS: We used HG peritoneal dialysis fluid (PDF) to induce in vivo PF in mice, and treated HPMCs with HG in vitro to stimulate EMT. RESULTS: In the mice, the higher the glucose concentration in the dialysate, the more obvious the peritoneal tissue thickening and the more that collagen was deposited. The in vitro study indicated that the expression of IGF-1R, α-SMA, vimentin was upregulated, while the expression of occludin, ZO-1, and E-cadherin was downregulated in HPMCs under HG and IGF-1R overexpression conditions. Conversely, the expression of IGF-1R, α-SMA, and vimentin was downregulated, while the expression of occludin, ZO-1, and E-cadherin was upregulated in IGF-1R-underexpressed HPMCs under HG conditions. The cell migration abilities were increased, while the cell adhesion abilities were reduced in HPMCs under HG and IGF-1R overexpression conditions. In contrast, cell migration abilities were reduced, while cell adhesion abilities were increased in IGF-1Runderexpressed HPMCs under HG conditions. CONCLUSIONS: Targeting at IGF-1R may provide novel insights into the prevention and treatment of PF.

Angiotensin II type 2 receptor prevents extracellular matrix accumulation in human peritoneal mesothelial cell by ameliorating lipid disorder via LOX-1 suppression.

Evidence suggests that intracellular angiotensin II type 1 receptor (AT1) contributes to peritoneal fibrosis (PF) under high glucose (HG)-based dialysates. It is generally believed that AT2 antagonisticly affects AT1 function. The aim of this study was to explore whether AT2 activation is beneficial for attenuating human peritoneal mesothelial cell (HPMC) injury due to HG. We treated a HPMC line with HG to induce extracellular matrix (ECM) formation. AT2 was increased and blocked using CGP42112A and AT2 siRNA. Lipid deposition was detected, signaling molecules associated with lectin-like oxidized lipoprotein receptor-1 (LOX-1) and ECM proteins were evaluated by real-time PCR and western blot. The results showed that HG led to AT2 inhibition in HPMCs, inhibition of AT2 further aggravated the expression of ECM proteins, including α-smooth muscle actin, fibroblast specific protein-1 and collagen I, while AT2 decreased the expression of ECM proteins, even during HG stimulation. Interestingly, there was a parallel change in lipid accumulation and ECM formation when AT2 was increased or depressed. Moreover, AT2-mediated decreased ECM production was associated with reduced lipid accumulation in HPMCs and depended on the downregulation of LOX-1. Further analysis showed that HG increased oxidized low-density lipoprotein (ox-LDL) deposition in HPMCs concomitant with an enhanced expression of ECM components, whereas blocking LOX-1 reversed ox-LDL deposition even in the presence of HG. This effect was also accompanied by the remission of ECM accumulation. Our results suggested that AT2 prevented ECM formation in HG-stimulated HPMCs by ameliorating lipid via LOX-1 suppression.

Overexpression of Soybean GmWRI1a Stably Increases the Seed Oil Content in Soybean.

WRINKLED1 (WRI1), an APETALA2/ethylene-responsive-element-binding protein (AP2/EREBP) subfamily transcription factor, plays a crucial role in the transcriptional regulation of plant fatty acid biosynthesis. In this study, GmWRI1a was overexpressed in the soybean cultivar 'Dongnong 50' using Agrobacterium-mediated transformation to generate three transgenic lines with high seed oil contents. PCR and Southern blotting analysis showed that the T-DNA was inserted into the genome at precise insertion sites and was stably inherited by the progeny. Expression analysis using qRT-PCR and Western blotting indicated that GmWRI1a and bar driven by the CaMV 35S promoter were significantly upregulated in the transgenic plants at different developmental stages. Transcriptome sequencing results showed there were obvious differences in gene expression between transgenic line and transgenic receptor during seed developmental stages. KEGG analysis found that the differentially expressed genes mainly annotated to metabolic pathways, such as carbohydrated metabolism and lipid metabolism. A 2-year single-location field trial revealed that three transgenic lines overexpressing GmWRI1a (GmWRI1a-OE) showed a stable increase in seed oil content of 4.97-10.35%. Importantly, no significant effect on protein content and yield was observed. Overexpression of GmWRI1a changed the fatty acid composition by increasing the linoleic acid (C18:2) content and decreasing the palmitic acid (C16:0) content in the seed. The three GmWRI1a-OE lines showed no significant changes in agronomic traits. The results demonstrated that the three GmWRI1a overexpression lines exhibited consistent increases in seed oil content compared with that of the wild type and did not significantly affect the seed yield and agronomic traits. The genetic engineering of GmWRI1a will be an effective strategy for the improvement of seed oil content and value in soybean.

Activation of the RAS contributes to peritoneal fibrosis via dysregulation of low-density lipoprotein receptor.

Peritoneal dialysis (PD)-related peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation in peritoneal mesothelial cells (PMCs) during long-term use of high glucose (HG)-based dialysates. Activation of the renin-angiotensin system (RAS) has been shown to be associated with PF. The aim of this study was to explore the underlying mechanism of the RAS in HG-induced PF. We treated C57BL/6 mice and a human PMC line with HG to induce a PF model and to stimulate ECM accumulation, respectively. RAS activity was blocked using valsartan or angiotensin II (ANGII) type 1 receptor siRNA. The major findings were as follows. First, mice in the HG group exhibited increased collagen deposition and expression of ECM proteins, including α-smooth muscle actin (α-SMA) and collagen type I in the peritoneum. Consistent with the in vivo data, HG upregulated α-SMA expression in human peritoneal mesothelial cells (HPMCs) in a time- and dose-dependent manner. Second, HG stimulation led to RAS activation in HPMCs, and inactivation of RAS decreased the expression of ECM proteins in vivo and in vitro, even during HG stimulation. Finally, RAS-mediated ECM production was associated with lipid accumulation in HPMCs and depended on the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. HG-stimulated HPMCs showed increased coexpression of LDLr and α-SMA, whereas blockade of RAS activity reversed the effect. Furthermore, inhibition of LDLr signaling decreased α-SMA and collagen type I expression in HPMCs when treated with HG and ANG II. In conclusion, increased intracellular RAS activity impaired lipid homeostasis and induced ECM accumulation in HPMCs by disrupting the LDLr pathway, which contributed to PF.

Predictive value of live birth rate based on different intrauterine adhesion evaluation systems following TCRA.

OBJECTIVE: The aim of this study was to assess the predictive value of five different intrauterine adhesion (IUA) evaluation systems for live birth rate following transcervical resection of adhesion (TCRA). METHOD: This retrospective study included 128 women with IUA who desired for spontaneous conception after TCRA. All the patients were retrospectively scored by the American Fertility Society (AFS) classification, European Society of Gynecological Endoscopy (ESGE) classification, March's classification (March), Nasr classification (Nasr) and Chinese IUA diagnosis classification criteria (Chinese). The predictive value of these evaluation systems was determined by receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). RESULTS: The correlation coefficients of AFS, ESGE, March, Nasr and Chinese classification and the live birth rate were 0.313, 0.313, 0.288, 0.380, and 0.336, respectively. Among women with hypomenorrhea and amenorrhea, as well as women with no infertility, the severities determined by all five evaluation systems were correlated with live birth rate (P <  0.001). All five scoring systems were efficient to predict live birth rate. Among them, Nasr classification showed the highest AUC (0.748) with the best predictive value. Multivariate logistic regression analyses showed that Nasr classification had the highest OR (OR, 6.523; 95% CI, 2.612, 18.263). And, Nasr's classification system also showed highest sensitivity (81.8%) and negative predictive value (96.7%) when divide the system into mild IUA vs. moderate and severe IUA. CONCLUSION: AFS, ESGE, March, Nasr and Chinese classification were demonstrated to be capable of predicting live birth following TCRA although the predictive capacities might be limited, and Nasr classification showed the highest predictive value of live birth.

The expression and clinical significance of TPM4 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is known as the fifth most common cancer in the world for its poor prognosis. New diagnostic markers and treatments are urgent to discover. To evaluate the protein expression of Tropomyosin4 (TPM4) and investigate its prognostic value in HCC, we collected 110 patients with different degrees of HCC and 10 patients with normal hepatic tissues and performed immunohistochemistry. Western bot was used to evaluate the expression of TPM4 in three HCC cell lines (HepG2, Huh7, SMMC-7721) and normal liver cell line LO2, as well as 7 HCC tissues and 7 normal hepatic tissues. The results of TPM4 staining revealed that TPM4 expression in HCC was higher than that in normal hepatic tissues, which was positive in 51.8% (n=57) and negative in 48.2% (n=53) while in normal hepatic tissues positive staining was in 10% (n=1) and negative staining was in 90% (n=9) (P=0.011). And the expression of TPM4 was related to pT status, grade and stage (P<0.001, P=0.015 and P<0.001, respectively). Western blot results indicated that TPM4 was high expressed in HCC cell line and HCC tissues. In conclusion, we believe that TPM4 can be applied as a diagnostic and prognostic marker to assist the management of HCC.

Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery.

Polyethylenimine (PEI) is a promising delivery vector of nucleic acids, but cytotoxicity and only moderate transfection efficacy with small RNAs limit its applications. Here we hypothesized that hydrophobization of PEI by combined modification with perfluorinated moieties (F) and cholesterol (Ch) will help in addressing both the cytotoxicity and siRNA delivery efficacy. To test the hypothesis, we synthesized a series of copolymers (F-PEI-Ch) by modifying PEI by reaction with heptafluorobutyric anhydride and cholesteryl chloroformate. We investigated and compared the effect of the modifications on siRNA delivery in vitro and in vivo. We found that the F-PEI-Ch copolymers assembled into micellar structures and that the copolymer with the highest Ch content exhibited the best siRNA delivery performance, including lower cytotoxicity, enhanced cell uptake, improved endosomal escape, and the best siRNA silencing efficacy in vitro and in vivo when compared with control PEI, F-PEI, and PEI-Ch. Overall, hydrophobization of PEI with a combination of cholesterol and superhydrophobic perfluorinated moieties represents a promising approach to the design of siRNA delivery vectors with decreased toxicity and enhanced transfection efficacy.

Intestinal fistula accompanied by recurrent peritonitis associated with peritoneal dialysis: a case report.

BACKGROUND: Intestinal perforation from peritoneal dialysis is rare, but the resulting complications are serious. Some patients do not necessarily have symptoms, and it can be difficult to differentiate their condition from PD-related (peritoneal dialysis-related) peritonitis, which may lead to misdiagnosis. Here we report a peritoneal dialysis patient with intestinal fistula associated with recurrent peritonitis. CASE PRESENTATION: A 44-year-old man had been treated for more than 6 years with peritoneal dialysis for chronic kidney disease stage-V. Abdominal computed tomography and electronic colonoscopy revealed an appendiceal fossa with adjacent fistula. The peritoneal dialysis catheter was removed, and the patient recovered with no recurrence of complications. CONCLUSION: We report a case of a rare complication of peritoneal dialysis. The intestinal fistula in this patient was mainly caused by recurrent peritonitis and removal of the catheter could control the peritonitis.

Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (TUG1), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of TUG1 in PCOS remains unclear. Herein, TUG1 expression was assayed in granulosa cells (GCs) of 100 patients with PCOS and 100 control participants. Receiver operating characteristic (ROC) curve analysis was conducted to determine the diagnostic value of TUG1 in PCOS. TUG1 expression was also silenced in KGN cells to explore the role of TUG1 in cellular proliferation, apoptosis, cell-cycle progression, autophagy, and steroidogenesis. We found that TUG1 levels were dramatically increased in the PCOS group compared with those of the control group; this increased expression was related to a rising antral follicle count (R = 0.209, P < 0.001 versus control). The ROC curve indicated a significant separation between PCOS group and the control group (AUC: 0.702; 95% CI: 0.630-0.773; P < 0.001). TUG1 showed a predominantly nuclear localization in human GCs. TUG1 knockdown reduced cellular proliferation, and promoted MAPKs pathway-dependent apoptosis and P21-dependent autophagy, but may not affect cell-cycle progression. TUG1 knockdown increased aromatase expression and oestradiol biosynthesis. Our results indicate that increased TUG1 expression in PCOS GCs may contribute to excessive follicular activation and growth, and may disrupt the selection of dominant follicle. Our study shows that TUG1 can be used as a diagnostic biomarker for PCOS.

Mitochondria-mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase.

Lung cancer is the main health threat in the world. Recently, oleuropein has been reported to have potent antioxidant and anticancer activities. However, the antitumor effects of oleuropein on H1299 cells are not well understood. Therefore, the purpose of this paper is tantamount to explore the effects of oleuropein on H1299 cells and its underlying mechanism that may be involved. Oleuropein treatment in H1299 cells resulted in cell cycle distribution at G2 /M arrest and apoptosis in a dose-dependent manner. Mitochondria-mediated apoptosis was verified by the increase in Bax/Bcl-2 ratio, release of cytochrome c, and activation of caspase-3 on oleuropein-induced H1299 cells. In addition, our data also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway has a critical role in oleuropein-induced apoptosis. Moreover, we used transcriptome analysis to identify differentially expressed genes (DEGs) in H1299 cells by oleuropein and SB203580 treatment. Many DEGs were annotated to metabolic pathways, cell cycle, pathways in cancer, MAPK signaling pathway by Kyoto Encyclopedia of Genes and Genomes and Gene ontology enrichment methods. Network and expression analysis found that DEGs, including RPS6A5, GADD45A, and MKP, play a key role in the p38 MAPK signaling pathway. In H1299 cells, oleuropein resulted in the expression of numerous genes related to cell signaling, metabolism pathway and directly associated with apoptosis. These results illustrated that oleuropein-induced apoptosis via mitochondrial apoptotic cascade was activated by the p38 MAPK signaling pathway in H1299 cells. Thus, oleuropein as a natural compound and therapeutic drug has potential application value in the treatment of lung cancer.