Associations of Urinary Nickel with NAFLD and Liver Fibrosis in the USA: A Nationwide Cross­Sectional Study.

Despite the robust correlation between metabolic disorders and heavy metals, there has been limited research on the associations between nickel levels and non-alcoholic fatty liver disease (NAFLD) as well as liver fibrosis. This study aimed to examine the associations among urinary nickel, NAFLD, and liver fibrosis. The data utilized in this study were obtained from the National Health and Nutrition Examination Survey 2017-2020. A comprehensive screening process was conducted, resulting in the inclusion of a total of 3169 American adults in the analysis. The measurement of urinary nickel was conducted through inductively coupled-plasma mass spectrometry. Vibration-controlled transient elastography was employed to assess the controlled attenuation parameter and liver stiffness measurement as indicators for NAFLD and liver fibrosis, respectively. Multivariable logistic regression models were employed to evaluate the associations among urinary nickel, NAFLD, and liver fibrosis. Restricted cubic splines were employed to explored the nonlinear associations. After adjusting for all covariates, the correlation between the highest quartile of urinary nickel and NAFLD was found to be significant (OR = 1.65; 95% CI, 1.19-2.27). Subgroup analysis revealed that the correlation was significant only in men. A significant association occurred between the second quartile of urinary nickel and liver fibrosis (OR 1.88; 95% CI, 1.22-2.90). Restricted cubic spline showed that the relationship was linear between urinary nickel and NAFLD and non-monotonic, inverse U-shaped between urinary nickel and liver fibrosis. This cross-sectional study indicated that the risk of NAFLD is associated with urinary nickel, and this correlation was only present among males.

MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3.

The etiology of numerous metabolic disorders is characterized by hepatic insulin resistance (IR). Uncertainty surrounds miR-34a's contribution to high-fat-induced hepatic IR and its probable mechanism. The role and mechanism of miR-34a and its target gene ENO3 in high-fat-induced hepatic IR were explored by overexpressing/suppressing miR-34a and ENO3 levels in in vivo and in vitro experiments. Moreover, as a human hepatic IR model, the miR-34a/ENO3 pathway was validated in patients with non-alcoholic fatty liver disease (NAFLD). The overexpression of hepatic miR-34a lowered insulin signaling and altered glucose metabolism in hepatocytes. In contrast, reducing miR-34a expression significantly reversed hepatic IR indices induced by palmitic acid (PA)/HFD. ENO3 was identified as a direct target gene of miR-34a. Overexpression of ENO3 effectively inhibited high-fat-induced hepatic IR-related indices both in vitro and in vivo. Moreover, the expression patterns of members of the miR-34a/ENO3 pathway in the liver tissues of NAFLD patients was in line with the findings of both cellular and animal studies. A high-fat-induced increase in hepatic miR-34a levels attenuates insulin signaling and impairs glucose metabolism by suppressing the expression of its target gene ENO3, ultimately leading to hepatic IR. The miR-34a/ENO3 pathway may be a potential therapeutic target for hepatic IR and related metabolic diseases.

Can Epstein-Barr virus-deoxyribonucleic acid load after induction chemotherapy combined with American Joint Committee on Cancer stage determine the chemotherapy intensity of locally advanced nasopharyngeal carcinoma?

BACKGROUND: Induction chemotherapy (IC) comprising docetaxel, cisplatin, and fluorouracil (TPF), combined with concurrent chemoradiotherapy (CCRT) effectively improves the survival rate of locally advanced nasopharyngeal carcinoma (LA-NPC). Selecting patients whose risk of tumor recurrence and metastasis is high and the appropriate chemotherapy intensity is a concern. We combined tumor-node-metastasis staging with the load of Epstein-Barr virus (EBV) after IC to select the individualized chemotherapy strength. METHODS: The clinical data and prognostic factors of patients with stage III-IV LA-NPC treated with TPF IC combined with CCRT were analyzed retrospectively. The conventional treatment group received the standard three cycles TPF IC combined with CCRT. For the new treatment group, the cycles of IC were determined according to whether the EBV-DNA disappeared completely after a certain course of IC, if so, subsequent IC was stopped and the chemoradiotherapy stage was entered. Propensity score matching (PSM) was performed at a ratio of 1:1 to balance baseline characteristics. Survival outcomes and adverse events between the conventional treatment group and the new method treatment group were compared. RESULTS: The study included 256 patients, among whom 192 were matched successfully into 96 pairs. The patients were followed up for a median of 51 months. The proportions of patients receiving three, two, and one cycle of IC after PSM in the routine and new treatment cohorts were 93.8%, 3.1%, 3.1% versus 21.9%, 49.0%, 24.0%, respectively. However, their 3-year distant metastasis-free survival, local recurrence-free survival, progression-free survival, and overall survival did not differ significantly. The incidence of grade 3-4 neutropenia toxicity in CCRT decreased significantly in patients receiving the new treatment method compared with that in the conventional treatment group (p = 0.026). CONCLUSION: Combining TNM stage and EBV-DNA load after IC to determine the courses of IC in patients with LA-NPC did not alter the curative effect but decreased toxicity.

Explore the Usefulness of Concurrent Chemotherapy in Stage II Nasopharyngeal Carcinoma: A Retrospective Study.

Objective: This study aims to compare the treatment outcomes of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in stage II nasopharyngeal carcinoma (NPC) patients. Methods: We retrospectively collected 601 stage II NPC patients treated in two hospitals between June 2003 to June 2016. All patients were divided into the CCRT group (n = 255) and the RT group (n = 346). Overall survival (OS), locoregional failure-free survival (LRFFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. The log-rank test was used to compare the differences between the groups. The Cox-regression hazards model was performed to determine potential prognostic factors. Results: The median follow-up was 99 months. No significant difference was found in locoregional recurrence, distant metastasis, disease progression, and death between the two groups (all p > 0.05). In univariate analysis, the 5-years OS, PFS, LRFFS, and DMFS had no significant differences between the CCRT and RT groups (all p > 0.05). Two-dimensional radiotherapy (2DRT) sub-analysis showed that CCRT remarkably increased DMFS, PFS, and OS rates (all p < 0.05) but not LRFFS (p = 0.258) compared with RT alone. While intensity-modulated radiotherapy (IMRT) sub-analysis showed that the prognosis of the two groups had no significant differences (all p > 0.05). In multivariate analyses, age was significantly and inversely related to OS, PFS, LRFFS, and DMFS. IMRT was an independent favorable factor for improving LRFFS, PFS, and OS. Concurrent chemotherapy was an independent protective factor for DMFS. Conclusion: In the context of 2DRT, it is definite that concurrent chemotherapy provides survival benefits for patients with stage II NPC. While in the IMRT era, the impact of chemotherapy on survival in patients with stage II NPC is weakened. Prospective randomized controlled studies are required to confirm these results.

Hydrogen Clathrate Structures in Uranium Hydrides at High Pressures.

Room-temperature superconductivity has always been an area of intensive research. Recent findings of clathrate metal hydrides structures have opened up the doors for achieving room-temperature superconductivity in these materials. Here, we report first-principles calculations for stable H-rich clathrate structures of uranium hydrides at high pressures. The clathrate uranium hydrides contain H cages with stoichiometries of H24, H29, and H32, in which H atoms are bonded covalently to other H atoms, and U atoms occupy the centers of the cages. Especially, a UH10 clathrate structure containing H32 cages is predicted to have an estimated T c higher than 77 K at high pressures.

Anatomical and Histological Study of the Conjoint Fascial Sheath of the Levator and Superior Rectus for Ptosis Surgery.

PURPOSE: An anatomical and histological study of the conjoint fascial sheath of the levator and superior rectus (CFS) was carried out by using the cadavers for teaching. METHODS: Three adult Asian cadaver heads fixed in formalin were used. The CFS was exposed by the same surgeon in each case. Then the CFS was observed and measured in vivo and ex vivo. And the CFS, the levator and the frontal muscle were removed from the same eye for histological study. RESULTS: The CFS was located 2.1 ± 0.4 mm posterior to the fornix. A special muscle sheath of the levator was observed. The special muscle sheath and the tendon of the superior rectus were fused to the CFS through loose connective tissue. Hematoxylin-Eosin (HE) staining showed a large amount of connective tissue on examination of the CFS by microscopy. Double staining with Victoria-blue and Masson trichrome staining confirmed elastic fibers and collagen fibers in the CFS tissues. CONCLUSIONS: If ptosis correction surgery is performed by looking for the CFS from the upper edge of the conjunctiva, in fact, only a special part of the muscle sheath of the levator in the CFS, but not the integral CFS, is used in the surgery. The histological results confirm that the CFS is a fibrous tissue membrane with both elasticity and toughness. Perhaps the best choice is to recombine the special muscle sheath of the levator in the CFS with the levator muscle tissue during ptosis correction surgery to suspend the eyelids.

MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. METHODS: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. RESULTS: MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, ß-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. CONCLUSIONS: BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.

[Performance, Sludge Characteristics, and the Microbial Community Dynamics of Bulking Sludge Under Different Nitrogen and Phosphorus Imbalances].

In this paper, the performance, characteristics of the bulking sludge, and the variations in the microbial community (including the bulking bacteria) under different nitrogen and phosphorus imbalances were compared, using high-throughput sequencing (16S rRNA) and the high performance liquid chromatography (HPLC) technology. The results showed that after seeding bulking sludge in the A/O process and operating for a period of time, the sludge settleability of the nitrogen limitation alone reactor (RN) could recover to normal[sludge volume index (SVI)<150 mL·g-1], while the SVI of the phosphorus limitation alone reactor (RP) improved slightly; the control reactor (R0, C/N/P=100/5/1) exhibited the highest SVI index (SVI=1496 mL·g-1), followed by the reactor of simultaneous nitrogen and phosphorus limitations (RNP). Under normal nutritional conditions, Pearson correlation analysis showed a significant negative correlation between the lipopolysaccharide (LPS) relative content (LPS/MLVSS) and the settleability of bulking sludge (r=-0.625, P<0.05), while under nutrient limitation conditions, LPS showed high accuracy in reflecting the biomass of the activated sludge. Thiothrix was the dominant bulking bacteria in all the reactors. PCoA analysis showed that the migration of the community in the reactors experienced nitrogen limitation (RNP, RN) changes greatly during the stages Ⅱ and Ⅲ, while RDA analysis showed that the correlation of Thiothrix with the settling performance and oxygen consumption rate was significant.

[Inhibition of MCF-7/ADR cells by DOX-loaded pluronic-attached PAMAM dendrimer conjugate].

Pluronic modified polyamidoamine (PAMAM) conjugate (PF127-PAMAM) was prepared and the inhibiting effect of MDR against MCF-7/ADR was investigated with doxorubicin (DOX) as model drug. 1H NMR and FTIR spectra showed that the conjugate was synthesized successfully. Element analysis accurately measured that 27.63% amino of per PAMAM was modified by pluronic (PAMAM : PF127, 1 : 35.37 mole ratio). PF127-PAMAM showed an increased size and a reduced zeta potential compared to PAMAM. PF127-PAMAM had lower hemolytic toxicity and cytotoxicity due to the reduced zeta potential and the protection of PF127. Each PF127-PAMAM molecular could load 19.58 DOX molecules, and the complex exhibited sustained and pH-sensitive release behavior. PF127-PAMAM/DOX exhibited weaker cytotoxicity than free DOX in MCF-7 cells; while the complex showed much stronger reverse effect of drug resistance in MCF-7/ADR cells, and resistance reversion index (RRI) was as high as 33.15.