Aldehyde dehydrogenase 2 （ALDH2） is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal （4-HNE）. Using an unbiased proteomic search, we identified ALDH2 ...deficiency in stroke-prone spontaneously hypertensive rats （SHR-SP） as compared with spontaneously hypertensive rats （SHR）. We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2 conferred neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown rats revealed the ab- sence of neuroprotective effects of PKCε. Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE, and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway. In SHR-SP, serum 4-HNE level was persistently elevated and correlated inversely with the lifespan. The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke. These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects, and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.
The present study aimed to investigate the value of magnetic resonance imaging (MRI) in the diagnosis of giant cell tumor of the tendon sheath (GCTTS), including localized (L-) and diffuse (D-) ...types. A total of 38 patients with GCTTS, including 31 with L-GCTTS and 7 with D-GCTTS, diagnosed by surgery and pathology, were retrospectively analyzed. All patients underwent MRI examination. Of the 31 patients with L-GCTTS, the tumors were located in the hand and wrist (18 patients), the ankle and foot (10 cases), the knee joint (2 cases) and the temporomandibular joint (1 case). All 31 lesions were either located in relation to a tendon or were partially/completely enveloping it and all were well marginated. With respect to the 7 D-GCTTS patients, the tumors were located in the ankle and foot (6 cases) or the hand and wrist (1 cases). All 7 lesions presented as an aggressive soft tissue mass infiltrating the tendon sheath and adipose tissue around the joint. The characteristic internal signal of GCTTS, including L-GCTTS and D-GCTTS, was demonstrated by MRI examination. MRI is currently the optimal modality for preoperative assessment of tumor size, extent and invasion of adjacent joint and tenosynovial space.
The abnormal fear memory will lead to the onset of stress disorders, such as post-traumatic stress disorder (PTSD) and so on. Therefore, the intervention in the formation of abnormal fear memory will ...provide a new strategy for the prevention and treatment of PTSD. In our previous studies, we found that blockade of dopamine D3 receptor (DRD3) with highly selective antagonist YQA14 or knockout of DRD3 was able to attenuate the expression or retrieval of fear memory in PTSD animal models. However, the neurobiological mechanism of regulation of DRD3 in fear is unclear. In the present research, we clarified that DRD3 was expressed in the dopaminergic (DAergic) neurons in the ventral tegmental area (VTA). Then, we identified that microinjection of YQA14 (1 μg/0.2 μl/side) in VTA before the aversive stimuli in the training session or during days subsequent to the shock significantly meliorated the freezing behaviors in the inescapable electric foot-shock model. At last, using fiber photometry system, we found that microinjection of YQA14 in VTA promoted the dopamine neurotransmitter release in the basolateral amygdala (BLA), and pre-training YQA14 infusion in VTA lowered the increase of dopamine (DA) in BLA induced by shock during the training session or by context during the retrieval session. All above the results demonstrated that YQA14 attenuated the fear learning through the blockade of DRD3 in VTA decreasing the excitability of the projection to BLA. This study may provide new mechanisms and potential intervention targets for stress disorders with abnormal fear memory.
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•Improvement of DAergic Neurons in VTA attenuates fear memory through blocking DRD3.•Blockade of DRD3 in VTA prior to foot-shock reduces the increase of DA level in BLA.•Blockade of DRD3 may decline fear memory through the projection from VTA to BLA.
Abstract
It has long been known that the thermal catalyst Cu/ZnO/Al
2
O
3
(CZA) can enable remarkable catalytic performance towards CO
2
hydrogenation for the reverse water-gas shift (RWGS) and ...methanol synthesis reactions. However, owing to the direct competition between these reactions, high pressure and high hydrogen concentration (≥75%) are required to shift the thermodynamic equilibrium towards methanol synthesis. Herein, a new black indium oxide with photothermal catalytic activity is successfully prepared, and it facilitates a tandem synthesis of methanol at a low hydrogen concentration (50%) and ambient pressure by directly using by-product CO as feedstock. The methanol selectivities achieve 33.24% and 49.23% at low and high hydrogen concentrations, respectively.
Induction of cell death and inhibition of cell growth are the main targets of cancer therapy. Here we evaluated the role of autophagy on chemoresistance of human hepatocarcinoma (HCC) cell lines, ...focusing on its crosstalk with cell apoptosis and proliferation. In this study, a chemotherapeutic agent (cisplatin or 5FU) induced the formation of autophagosomes in three human HCC cell lines and upregulated the expression of autophagy protein LC3-II. Inhibition of autophagy by 3-methyladenine or si-beclin 1 increased chemotherapy-induced apoptosis in HCC cells. Meanwhile, increased damage of the mitochondrial membrane potential was also observed in HCC cells when autophagy was inhibited. Furthermore, inhibition of autophagy reduced clone formation and impaired cell growth of HCC cells when treated with chemotherapy. Co-administration of an autophagy inhibitor (chloroquine) and chemotherapy significantly inhibited tumor growth in a mouse xenograft tumor model, with greater extent of apoptosis and impaired proliferation of tumor cells. This study suggests that autophagy is a potential novel target to improve therapy efficiency of conventional chemotherapeutics towards HCC.
Abstract
Background
Cervical cancer is the second most common female malignant tumor in the world. According to a study in 2018, the incidence of cervical cancer in Yunnan Province of China was 11.42 ...per 100,000, the mortality rate was 3.77 per 100,000, and higher than the national average. Health-related quality of life (HRQoL) can be used not only in the selection and effect evaluation of clinical treatment plans of cervical cancer, but also in the evaluation of prognosis and long-term survival status. In this study, 288 cervical cancer patients admitted to the Yunnan Cancer Hospital in Southwest China from 2018 to 2020 were used as the survey objects to understand the HRQoL of cervical cancer patients and explore the related factors that affect HRQoL.
Methods
The Chinese version of the functional assessment of cancer therapy-cervix (functional assessment of cancer therapy-cervix v4.0, FACT-Cx V4) was used to investigate 288 patients with cervical cancer in Yunnan Province. Statistical analysis was performed using t-test, analysis of variance, multiple linear regression and other methods.
Results
The total FACT-Cx score of cervical cancer patients was (130.16 ± 14.20), the physical well-being (PWB) score was (22.02 ± 4.47), the social/family well-being (SWB) score was (25.66 ± 3.59), the emotional well-being (EWB) score was (19.75 ± 3.54), the functional well-being (FWB) score was (16.91 ± 5.01) and the additional focus area (cervical cancer subscale, CxS) score was (45.78 ± 4.61). From the multi-factor analysis results, the scores of PWB, FWB, Cxs and the total FACT-Cx were related to the choice of different treatment methods, the PWB scores of patients with concurrent chemoradiotherapy was low(β = − 1.67,
P
= 0.003), the FWB scores of patients with concurrent chemoradiotherapy was low(β = − 2.02,
P
= 0.001), the CxS scores of patients with concurrent chemoradiotherapy was low(β = − 1.61,
P
= 0.006), the total score of FACT-Cx of patients with concurrent chemoradiotherapy was low(β = − 5.91,
P
= 0.001). SWB score was affected by marital status, married patients had high PWB scores(β = 5.44,
P
= 0.006). The patients with heavy disease expenditures as aproportion of family disposable income(β = − 3.82,
P
= 0.002) and aged 60 and above(β = − 3.29,
P
= 0.003) had lower FWB scores. The total score FACT-Cx of patients participating in cervical cancer screening was higher(β = 7.61,
P
= 0.001).
Conclusion
The choice of treatment method is the common influencing factor of PWB, FWB, Cxs and the total FACT-Cx. Disease expenditures as a proportion of family disposable income, the treatment method, the marital status and whether to participate in cervical cancer screening affect the patient’s evaluation of their own HRQoL. Medical staff should pay special attention to the choice of different treatment methods, popularize vaccination knowledge and cervical cancer screening, give more humanistic care and health education to cervical cancer patients who have low education level, poor economic conditions, divorced or separated, and encourage patients to participate in active treatment to improve the health-related quality of life.
•Two steps sampling method was proposed for blade measurement.•Leading edge and trailing edge represent the twisted and bend information of blade.•Chordal deviation criterion was used to sampling ...sectional curves.•The method proposed can reduce the measurement point significantly.
Blade is one of the most important parts in turbine machinery. The complex geometry of blades not only makes them difficult to fabricate, but also leads them difficult to inspect. Typically, the surface of blades is measured by using coordinate measuring machine (CMM). Since the measurement time and cost increase proportionally as the increase of measurement points, it is essential to sample measurement points which can represent entire blade with sufficient confidence and accuracy. In order to achieve a certain allowable deviation with a suitable set of points, a practical sampling method for surface measurement of blades was studied. Firstly, the leading edge curve and trailing edge curve were supposed to represent the twisted and bend information of blades. A sampling method based on maximum chordal deviation for leading edge curve and trailing edge curve was researched. Further, a fusion approach for sampling points on both edge curves, which determine the cross-sections, was proposed. Secondly, the inspection points sampling method for sectional curves were investigated. Finally, two simulation and one experimental examples were used to demonstrate the sampling methodology. The results indicated that the approach of this study can ensure the measurement precision at high curvature potion by measuring a small number of points.
Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia ...reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H2O2. Overexpression of H19 alleviated myocardial I/RI of mice and cardiomyocyte injury induced by H2O2. We found that H19 functioned as a competing endogenous RNA of miR-877-3p, which decreased the expression of miR-877-3p through the base-pairing mechanism. In parallel, miR-877-3p was upregulated in H2O2-treated cardiomyocytes and mouse ischemia reperfusion (I/R) hearts. miR-877-3p exacerbated myocardial I/RI and cardiomyocyte apoptosis. We further established Bcl-2 as a downstream target of miR-877-3p. miR-877-3p inhibited the mRNA and protein expression of Bcl-2. Furthermore, H19 decreased the Bcl-2/Bax ratio at mRNA and protein levels, cytochrome c release, and activation of caspase-9 and caspase-3 in myocardial I/RI mice, which were canceled by miR-877-3p. In summary, the H19/miR-877-3p/Bcl-2 pathway is involved in regulation of mitochondrial apoptosis during myocardial I/RI, which provided new insight into molecular mechanisms underlying regulation of myocardial I/RI.
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The turbine blade is one of the most important parts in turbine machinery. Casting deformation is an important index to evaluate the quality of the turbine blade. In order to control the deformation ...of the turbine blade during investment casting, a novel compensation method based on reverse deformation was proposed in this study. Firstly, the process of deformation compensation was discussed. To overcome the disadvantage of the iteration compensation process, a one-step compensation model was developed based on Taylor expansion. Moreover, a smooth deformation function for the compensation model was regressed based on casting simulation results. Finally, two blades were optimized according to the proposed methodology. The deformations before and after compensation were compared. The results indicated that the casting deformation was reduced significantly. Hence, a more accurate blade can be achieved.
Angiogenesis inhibitors have long been considered desirable anticancer agents. However, it was found that many tumors could develop resistance to antiangiogenesis inhibitors. Antiangiogenic therapy ...results in metabolic stress. Autophagy is an important survival mechanism in cancer cells under metabolic stress; however, it remains unknown if autophagy contributes to antiangiogenesis resistance. In this study, we reported that bevacizumab treatment reduced the development of new blood vessels and inhibited cell growth in xenografts of hepatocellular carcinoma (HCC) tumors. Bevacizumab treatment also upregulated expression of the autophagy-related genes (Beclin1 and LC3) and increased autophagosome formation. Our in vitro studies demonstrated that autophagy inhibition significantly increased apoptosis of HCC cells during nutrient starvation or hypoxia. In addition, the combined treatment of an autophagy inhibitor and bevacizumab markedly inhibited the tumor growth of HCC xenografts, led to enhanced apoptosis, and impaired the proliferation of tumor cells compared with treatment with either drug alone. Furthermore, autophagy inhibition led to enhanced reactive oxygen species (ROS) generation in HCC cells exposed to nutrient starvation or hypoxia in vitro and increased DNA oxidative damage in vivo. Antioxidants reduced nutrient starvation or the hypoxia-induced cell death of HCC cells after autophagy inhibition. Our results suggest that autophagy modulates ROS generation and contributes to cell survival under metabolic stress. Therefore, autophagy inhibition may be a novel way of increasing the efficicacy of antiangiogenic agents in the treatment of HCC.
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