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Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8+ T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8+ T cells, MFN2 enhances mitochondria–endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca2+-ATPase SERCA2, facilitating the mitochondrial Ca2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8+ T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8+ T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function. Editor's summary: Organelle cross-talk plays a fundamental role in cell biology, but how this cross-talk controls tumor-infiltrating CD8+ T cells (TILs) is not understood. Yang et al. investigate the role of MFN2 in CD8+ TILs, identifying that mitochondrial interaction with the endoplasmic reticulum (ER) is required for metabolic fitness and antitumor activity. Through interaction with SERCA2 on the ER, MFN2 was required for mitochondria-ER contact and Ca2+ homeostasis. MFN2 expression was associated with better survival in patients with cancer, and promoting MFN2 expression in CD8+ T cells improved response to immune checkpoint blockade in mice. Together, these findings identify a critical role for MFN2 in regulating the metabolism, function, and survival of CD8+ T cells and suggest that boosting MFN2 expression is an attractive avenue for improving immunotherapy. —Hannah Isles [ABSTRACT FROM AUTHOR]

The experiment was to explore the effect of different fat sources in diet on growth of Ctenopharyngodon idella, Mylopharyngodon piceus and Carassius auratus gibelio, as well as conventional muscle nutrients and fatty acid composition. A total of 240 fish with an initial body weight of (34.8±0.4) g Ctenopharyngodon idella, (35.0±0.4) g Mylopharyngodon piceus, (26.3±0.1) g Carassius auratus gibelio were randomly divided into four groups with three replicates in each group and 60 fish in each replicate (three species mixed culture, 20 fish per species). The basic diet (BD group) without oil and fat was used as control group, and 6% soybean oil (SO group), fish oil (FO group) and lard (LO group) were added to basic diet as test groups. The experiment lasted for 8 w. The results showed that the average survival rate of the three species of fish in each group was significantly higher than that in BD group (P<0.05), and the survival rate of Mylopharyngodon piceus in test group was significantly higher than that in BD group (P<0.05). The total final weight and average weight gain of the three fish in each group were significantly higher than that in BD group (P<0.05). The feed coefficient of each group was significantly lower than that in BD group (P<0.05). The visceral body ratio and liver body ratio of Ctenopharyngodon idella in FO group were significantly higher than those in BD group (P<0.05), and the visceral body ratio and liver body ratio of Mylopharyngodon piceus in LO group were significantly higher than those in BD group (P<0.05). The visceral body ratio of Carassius auratus gibelio in BD group was significantly lower than that in other groups (P<0.05), and the liver to body ratio of Carassius auratus gibelio in FO group was significantly lower than that in other groups (P<0.05). The crude protein content of Ctenopharyngodon idella in FO group was significantly higher than that in BD group and SO group (P<0.05), and the crude protein content of Mylopharyngodon piceus in SO group was significantly lower than that in other groups (P<0.05). The crude fat content of Ctenopharyngodon idella in LO group was significantly higher than that in other groups (P<0.05), and the crude fat content of Mylopharyngodon piceus in SO group was significantly higher than that in other groups (P<0.05). The content of C16:0 was the highest in the three fish muscle fatty acids, followed by C18:1n-9, C18:0 and C18:2n-6. The content of C18: 2n-6, C18:3n-3 in SO group were significantly higher than other groups (P<0.05). The content of C20: 5n-3, C22:6n-3 in FO group were significantly higher than other groups (P<0.05). The content of C16:0, C18:1n-9 in LO group were significantly higher than those in other groups (P<0.05). The study indicates that adding fish oil to Ctenopharyngodon idella bait has a good growth-promoting effect, but adding 6% soybean oil and lard has no obvious growth-promoting effect, which indicates that Ctenopharyngodon idella has lower requirements for feed fat level. Adding 6% soybean oil, fish oil and lard to Mylopharyngodon piceus bait has better growth-promoting effect. Adding 6% fish oil and lard to Carassius auratus gibelio has better growth-promoting effect, but soybean oil has poor effect. [ABSTRACT FROM AUTHOR]

Evaluation of surrounding rock stability is a complicated system problem involving various uncertain factors. To overcome the drawbacks of conventional evaluation methods based on single-type information, a new combination evaluation method based on set pair analysis was proposed. This method made full use of available information sources from the different conventional methods while avoiding the most erroneous evaluation. First, the problem was treated with the single-type evaluation methods. Then, the set pair consisting of double evaluation results was analyzed on the identical-discrepancy-contrary principle to establish a connectional matrix. And the weights of the realted single-type evaluation methods in the comprehensive model were determined respectively through the connectional matrix. Finally the surrounding rock stability level was evaluated with the linear combination method. The results of the application case show that the proposed model is effective and feasible in improving the prediction accuracy through coupling the advantages of the related conventional evaluation methods. This method makes a good reference for other similar evaluation problems. [ABSTRACT FROM AUTHOR]

BACKGROUND Previous research has shown that fresh milk might be polluted by some organophosphorus pesticides (OPPs). In this study the dissipation of nine OPPs, namely chlorpyrifos, chlorpyrifos-methyl, diazinon, dichlorvos, fenthion, malathion, phorate, pirimiphos-methyl and trichlorphon, in skimmed milk was investigated to clarify their susceptibility towards lactic acid bacteria (LAB) and yogurt starters. RESULTS Skimmed milk was spiked with nine OPPs, inoculated with five strains of LAB and two commercial yogurt starters at 42 °C for 24 and 5 h respectively and subjected to quantitative OPP analysis by gas chromatography. Degradation kinetic constants of these OPPs were calculated based on a first-order reaction model. OPP dissipation in the milk was enhanced by the inoculated strains and starters, resulting in OPP concentrations decreasing by 7.0-64.6 and 7.4-19.2% respectively. Totally, the nine OPPs were more susceptible to Lactobacillus bulgaricus, as it enhanced their degradation rate constants by 18.3-133.3%. Higher phosphatase production of the assayed stains was observed to bring about greater OPP degradation in the milk. CONCLUSION Both LAB and yogurt starters could enhance OPP dissipation in skimmed milk, with the nine OPPs studied having different susceptibilities towards them. Phosphatase was a key factor governing OPP dissipation. The LAB of higher phosphatase production have more potential to decrease OPPs in fermented foods. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) constitutes a life-threatening condition, and identifying the ruptured aneurysm is essential for further therapy. This study aimed to evaluate the diagnostic accuracy of hypo-attenuating berry sign (HBS) observed on computed tomography (CT) scan in distinguishing ruptured aneurysms., Methods: In this diagnostic accuracy study, patients who had SAH and underwent non-enhanced brain CT scan were recruited. The HBS was defined as a hypo-attenuating area with an identifiable border in the blood-filled hyper-dense subarachnoid space. The screening performance characteristics of HBS in identifying ruptured aneurysms were calculated considering the digital subtraction angiography (DSA) as the gold standard., Results: A total of 129 aneurysms in 131 patients were analyzed. The overall sensitivity and specificity of HBS in the diagnosis of aneurysms were determined to be 78.7% (95%CI: 73.1% - 83.4%) and 70.7% (95%CI: 54.3% - 83.4%), respectively. Notably, the sensitivity increased to 90.9% (95%CI: 84.3% - 95.0%) for aneurysms larger than 5mm. The level of inter-observer agreement for assessing the presence of HBS was found to be substantial (kappa=0.734). The diagnostic accuracy of HBS in individuals exhibited enhanced specificity, sensitivity, and reliability when evaluating patients with a solitary aneurysm or assessing ruptured aneurysms. The multivariate logistic regression analysis revealed a statistically significant relationship between aneurysm size and the presence of HBS (odds ratios of 1.667 (95%CI: 1.238 - 2.244; p < 0.001) and 1.696 (95%CI: 1.231 - 2.335; p = 0.001) for reader 1 and reader 2, respectively)., Conclusions: The HBS can serve as a simple and easy-to-use indicator for identifying a ruptured aneurysm and estimating its size in SAH patients.   ., Competing Interests: The authors declare that they have no conflicts of interest.

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8 + T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8 + T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca 2+ -ATPase SERCA2, facilitating the mitochondrial Ca 2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca 2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca 2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8 + T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8 + T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function.

Aim: To investigate the functional role and underlying molecular mechanism of miR-29a in hepatitis B virus (HBV) expression and replication., Methods: The levels of miR-29a and SMARCE1 in HBV-infected HepG2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8 (CCK-8) was used to detect the viability of HepG2.2.15 cells. The relationship between miR-29a and SMARCE1 were identified by target prediction and luciferase reporter analysis., Results: miR-29a promoted HBV replication and expression, while SMARCE1 repressed HBV replication and expression. Cell viability detection indicated that miR-29a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of miR-29a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by miR-29a overexpression., Conclusion: miR-29a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, miR-29a could be a promising therapeutic target for patients with HBV infection., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.