Tumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC).Multiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN.Patients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN "up-staged" the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set).TN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN "up-staged" the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients.
Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.
This paper presents a qualitative experimental research on start characteristics and flow control of a typical hypersonic inward-turning inlet. Designed at Ma6.5, the inlet is an ERST(Elliptical-to-Round Shape Transition) one, of which the internal contraction ratio and the total contraction ratio are 1.7 and 5.8, respectively. The throat section of the inlet is a round cross section with a diameter of 50mm. The whole length of the inlet is about 950mm. Using AHL3D CFD software, some numerical simulations are carried out, of which the result shows that the inlet can start but can't self-start at Ma5. Utilizing the same AHL3D, some researches of fluid bleeding on the inlet shoulder are conducted, of which the result shows that the inlet can self-start at Ma5 with a loss mass flow less than 1%. On the base of the numerical simulation, an inlet model with a scale of 1:1 is manufactured and some qualitative experiments are launched in a routine hypersonic blow-down wind tunnel of CARDC. By the means of the silk-thread flow visualization and the real-time throttle and the switch of the bleeding module, the start characteristics of the inlet with/without flow control are got from the experiments. The experiments verify the numerical result that the inlet can't self-start at Ma5 without bleeding. When the bleeding-area ratio is about 0.15, the inlet can self-start. The qualitative experiments also preliminarily verify the design method and the computational method of start characteristics for such inward-turning inlets. At the same time the results of the current experiments can provide a convenient and rapid silk-thread flow visualization method to judge the start states of an inlet in such routine wind tunnel.
Our research aims to investigate the associations between education level and osteoporosis (OP) in Chinese postmenopausal women.A large-scale, community-based, cross-sectional study was conducted to examine the associations between education level and OP. A self-reported questionnaire was used to access the demographical information and medical history of the participants. A total of 1905 postmenopausal women were available for data analysis in this study. Multiple regression models controlling for confounding factors to include education level were performed to investigate the relationship with OP.The prevalence of OP was 28.29% in our study sample. Multivariate linear regression analyses adjusted for relevant potential confounding factors detected significant associations between education level and T-score (β = 0.025, P-value = 0.095, 95% CI: -0.004-0.055 for model 1; and β = 0.092, P-value = 0.032, 95% CI: 0.008-0.175 for model 2). Multivariate logistic regression analyses detected significant associations between education level and OP in model 1 (P-value = 0.070 for model 1, Table 5), while no significant associations was reported in model 2 (P value = 0.131). In participants with high education levels, the OR for OP was 0.914 (95% CI: 0.830-1.007).The findings indicated that education level was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese postmenopausal women with low educational status.
Mitochondria are the powerhouse of the cell. They undergo fission and fusion to maintain cellular homeostasis. In this review, we explore the intricate regulation of mitochondrial fission at various levels, including the protein level, the post-translational modification level, and the organelle level. Malfunctions in mitochondrial fission can have detrimental effects on cells. Therefore, we also examine the association between mitochondrial fission with diseases such as breast cancer and cardiovascular disorders. We anticipate that a comprehensive investigation into the control of mitochondrial fission will pave the way for the development of innovative therapeutic strategies.
This study investigates the impact of twin intrahepatic cholestasis in pregnancy (ICP) in different chorionicity scenarios on pregnancy outcome and risk factors. This retrospective study was designed to investigate the association between ICP and pregnancy outcomes and associated risk factors. Logistic regression analysis was used to verify the correlation between ICP and pregnancy outcome and the associated risk factors with the risk of ICP. Pregnant women with ICP had less gestational weight gain (16.19 ± 5.28 vs 17.78 ± 7.19, P = .018), a smaller number of deliveries (16.26% vs 26.40%, P = .016), and less spontaneous pregnancy (50.41% vs 61.73%, P = .019). The mean birth weight of pregnant women without ICP was lower (2328.07 ± 461.82 vs 2404.70 ± 504.58, P = .023), and the prepregnancy hepatitis B virus (HBV) antigen carrying rate was lower (12.20% vs 6.16%, P = .021). Pregnancy weight gain (0.95 (0.92, 0.99) P = .009) and the number of weeks in labor (0.88 (0.81, 0.96) P = .003) were negatively associated with the risk of ICP. Assisted reproductive technology use (1.38 (0.70, 1.79) P = .635) and HBV carrier before pregnancy (2.51 (1.42, 4.48) P = .002) were positively associated with ICP risk. In monochorionic twins, those with ICP were more likely to have abnormal amniotic fluid (15.79% vs 2.16%, P = .012), while those without ICP were less likely to have abnormal amniotic fluid (0.90 (0.83, 0.97) P = .004). In double chorion twins, the incidence of preterm birth was higher in women with ICP (40.00% vs 24.14, P = .002), and the risk of preterm birth was reduced in women without ICP (0.87 (0.79, 0.96) P = .005). In terms of neonatal outcomes, women with ICP were more likely to have a stillbirth (5.26% vs 0.48% P = .037), and stillbirth was less likely to occur without ICP (0.95 (0.92, 0.98) P = .002). Our study illustrates that twin pregnancies with maternal comorbid ICP have lower birth weight, degree of weight gain during pregnancy and prepregnancy HBV carriage is strongly associated with the development of ICP. ICP contributes to adverse perinatal outcomes such as stillbirth, preterm labor, and differentiates between different chorionic twin pregnancy outcomes. The risk of ICP is differently affected by the degree of weight gain during pregnancy, gestational week of delivery, assisted reproductive technology, and prepregnancy HBV carriage.
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