Moderate replacement of fish oil with palmitic acid-stimulated mitochondrial fusion promotes ß-oxidation by Mfn2 interacting with Cpt1α via its GTPase-domain.

The mitochondrial matrix serves as the principal locale for the process of fatty acids (FAs) ß-oxidation. Preserving the integrity and homeostasis of mitochondria, which is accomplished through ongoing fusion and fission events, is of paramount importance for the effective execution of FAs ß-oxidation. There has been no investigation to date into whether and how mitochondrial fusion directly enhances FAs ß-oxidation. The underlying mechanism of a balanced FAs ratio favoring hepatic lipid homeostasis remains largely unclear. To address such gaps, the present study was conducted to investigate the mechanism through which a balanced dietary FAs ratio enhances hepatic FAs ß-oxidation. The investigation specifically focused on the involvement of Mfn2-mediated mitochondrial fusion in the regulation of Cpt1α in this process. In the present study, the yellow catfish (Pelteobagrus fulvidraco), recognized as a model organism for lipid metabolism, were subjected to eight weeks of in vivo feeding with six distinct diets featuring varying FAs ratios. Additionally, in vitro experiments were conducted to inhibit Mfn2-mediated mitochondrial fusion in isolated hepatocytes, achieved through the transfection of hepatocytes with si-mfn2. Further, deletion mutants for both Mfn2 and Cpt1α were constructed to elucidate the critical regions responsible for the interactions between these two proteins within the system. The key findings were: (1) Substituting palmitic acid (PA) for fish oil (FO) proved to be enhanced in reducing hepatic lipid accumulation. This beneficial effect was primarily attributed to the activation of mitochondrial FAs ß-oxidation; (2) The balanced replacement of PA stimulated Mfn2-mediated mitochondrial fusion by diminishing Mfn2 ubiquitination, thereby enhancing its protein retention within the mitochondria; (3) Mfn2-mediated mitochondrial fusion promoted FAs ß-oxidation through direct interaction between Mfn2 and Cpt1α via its GTPase-domains, which is essential for the maintenance of Cpt1 activity. Notably, the present research results unveil a previously undisclosed mechanism wherein Mfn2-mediated mitochondrial fusion promotes FAs ß-oxidation by directly augmenting the capacity for FA transport into mitochondria (MT), in addition to expanding the mitochondrial matrix. This underscores the pivotal role of mitochondrial fusion in preserving hepatic lipid homeostasis. The present results further confirm that these mechanisms are evolutionarily conserved, extending their relevance from fish to mammals.

Adherence to the Standards for Reporting of Diagnostic Accuracy Studies (STARD): a survey of four journals in laboratory medicine.

BACKGROUND: The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement has been updated in 2015. Many diagnostic test accuracy (DTA) studies have been published in medical laboratory journals, but their adherence to the updated STARD statement remains unknown. METHODS: We searched the PubMed database to verify studies published in 4 laboratory journals, including Clinical Chemistry, Clinical Chemistry and Laboratory Medicine, Clinica Chimica Acta, and Clinical Biochemistry, in 2019. DTA studies were identified and their adherence to the STARD statement was assessed. RESULTS: A total of 45 studies were included in this analysis. Overall, 18 out of 34 STARD items were reported. The items (adherence rate) of sample size estimation (4%), adverse events (9%), protocol (9%), registration (16%), missing value (22%), indeterminate results (18%), and cross-tabulation (22%) were the most frequently unreported items. CONCLUSIONS: Adherence to the STARD statement in DTA articles published in laboratory medicine seems as yet unsatisfactory. Our study emphasizes the necessity to improve the reporting quality of DTA studies published in medical laboratory journals.

Changes in circulating follicular helper T cells in peripheral blood of patients with acute hepatitis C virus infection.

BACKGROUND: To investigate the changes in circulating follicular helper T cells (cTfh) in peripheral blood of patients with acute hepatitis C virus (HCV) infection and its correlation with symptom severity of the disease. METHODS: A total of 105 subjects were enrolled in this study, including 35 healthy people, 35 patients with acute HCV infection and 35 acute HCV patients with antiviral therapy. Flow cytometry was used to detect the expression of molecular markers related to the surface of cTfh cells, such as CD69, HLA-DR and CD57, and ELISA was used to detect the secretion of cytokines (IL-21, IL-4) in each group. The relationship between these markers and disease was analyzed statistically. RESULTS: Flow cytometry analysis demonstrated that the percentage of CD69 in peripheral blood of patients with acute hepatitis C infection was (18.90%±9.29%) significantly higher than that of normal control group (5.10%±4.21%) and antiviral treatment group (11.50%±5.38%). The difference was statistically significant (P<0.05). The results of HLA-DR and CD57 were consistent with CD69. The serum levels of IL-4 and IL-21 in the acute HCV infection group were significantly higher than those in the treatment and the control groups. After antiviral treatment, IL-4 and IL-21 levels significantly decreased but remained higher than those in the control group. This showed that antiviral treatment was effective, and the difference was statistically significant (P<0.05). The ratio of cTfh in infected group was negatively correlated with HCV RNA content (r=-0.6858, P=0.0028). CONCLUSIONS: Antiviral immune response in patients with acute hepatitis C infection may be related to the proportion of T helper cells in peripheral blood circulation follicles. Dynamic detection of the number of T helper cells in clinical practice is conducive to identifying more effective methods to treat acute hepatitis C infection, which has important theoretical and clinical significance.

Variations of thermophysical properties and heat transfer performance of nanoparticle-enhanced ionic liquids.

The ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate ([EMIm]Ac) was investigated as a promising absorbent for absorption refrigeration. To improve the thermal conductivity of pure [EMIm]Ac, IL-based nanofluids (ionanofluids, INFs) were prepared by adding graphene nanoplatelets (GNPs). The thermal stability of the IL and INFs was analysed. The variations of the thermal conductivity, viscosity and specific heat capacity resulting from the addition of the GNPs were then measured over a wide range of temperatures and mass fractions. The measured data were fitted with appropriate equations and compared with the corresponding classical models. The results revealed that the IL and INFs were thermally stable over the measurement range. The thermal conductivity greatly increased with increasing mass fraction, while only slightly changed with increasing temperature. A maximum enhancement in thermal conductivity of 43.2% was observed at a temperature of 373.15 K for the INF with a mass fraction of 5%. The numerical results revealed that the dispersion of the GNPs in the pure IL effectively improved the local heat transfer coefficient by up to 28.6%.

A theory for spiral wave drift induced by ac and polarized electric fields in chemical excitable media.

Spiral waves are shown to undergo directional drifts in the presence of ac and polarized electric fields when their frequencies are twice of the spiral frequencies. Here, we propose a quantitative description for the spiral wave drift induced by weak electric fields, and provide the explicit equations for the spiral wave drift speed and direction. Numerical simulations are performed to demonstrate the quantitative agreement with analytical results in both weakly and highly excitable media.

Phase-locked scroll waves defy turbulence induced by negative filament tension.

Scroll waves in a three-dimensional media may develop into turbulence due to negative tension of the filament. Such negative tension-induced instability of scroll waves has been observed in the Belousov-Zhabotinsky reaction systems. Here we propose a method to restabilize scroll wave turbulence caused by negative tension in three-dimensional chemical excitable media using a circularly polarized (rotating) external field. The stabilization mechanism is analyzed in terms of phase-locking caused by the external field, which makes the effective filament tension positive. The phase-locked scroll waves that have positive tension and higher frequency defy the turbulence and finally restore order. A linear theory for the change of filament tension caused by a generic rotating external field is presented and its predictions closely agree with numerical simulations.

FZD2 inhibits the cell growth and migration of salivary adenoid cystic carcinomas.

Several studies have reported that FZD2 regulates tumor biology in a complex manner. The aim of the present study was to identify the role of FZD2 in the cell growth and metastasis of salivary adenoid cystic carcinomas (SACCs). The expression of FZD2 in ACC-83 and ACC-LM cells were measured with real-time PCR. Immunohistochemical staining was used to detect the expression of FZD2 in clinical SACC samples with or without metastasis. Cell proliferation and Transwell assays were performed to explore the effects of FZD2 on cell growth and migration following the silencing of FZD2 with small interference RNAs and the overexpression of FZD2 with plasmid. Our data showed that FZD2 was downregulated in ACC-LM cells, which are an adenoid cystic carcinoma cell line with high metastatic potential, compared to ACC-83 cells, which have low metastatic potential. Additionally, the expression of FZD2 was lower in SACC tissues with metastasis compared to SACC tissues without metastasis (P<0.05). Cell proliferation and migration of ACC-83 cells were increased after the knockdown of FZD2 and decreased following overexpression of FZD2. Knockdown of FZD2 downregulated the expression of PAI-1. Our results suggest that FZD2 may be a tumor suppressor gene in SACCs that inhibits cell growth and migration.

CDH12 promotes the invasion of salivary adenoid cystic carcinoma.

Cadherins are found in almost all living organisms. In addition to their role in the formation and maintenance of normal tissue architecture, cadherins seem to play a crucial role in the cell-cell interactions of cancer cells in tumorigenesis, invasion and metastasis. The aim of the present study was to identify the role of CDH12 in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that CDH12 is abnormally expressed in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. CDH12 expression was significantly higher in clinical samples with metastasis and recurrence than in those without metastasis and recurrence (P<0.05), as demonstrated by immunohistochemical analysis. Overexpression of the CDH12 protein in ACC-M cells infected with an adenovirus vector containing CDH12 enhanced the invasive and migratory ability of ACC-M cells in vitro compared to ACC-M cells infected with empty vector. Likewise, knockdown of CDH12 by small interfering RNA efficiently inhibited the invasion and migration of ACC-M cells in vitro. These results indicate that CDH12 may play an important role in the invasion and metastasis of SACC.

Notch-4 contributes to the metastasis of salivary adenoid cystic carcinoma.

The Notch signaling pathway is important for cell-cell communication; it is involved in gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Notch is present in all metazoans, and vertebrates possess four different Notch receptors: Notch-1, Notch-2, Notch-3, and Notch-4. The aim of the present study was to identify the role of Notch protein in the metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that Notch-1, Notch-2, and Notch-4 were upregulated in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. Knockdown of Notch-4 by small interfering RNA efficiently inhibited the invasion of ACC-M cells. Notch-4 expression was significantly higher in the clinical samples with metastasis and recurrence compared to that in control (p<0.05), shown by immunohistochemistry analysis. These results indicate that Notch-4 may play an important role in SACC metastasis.