MARCH5-mediated downregulation of ACC2 promotes fatty acid oxidation and tumor progression in ovarian cancer.

Lipid metabolic reprogramming has been recognized as a hallmark of human cancer. Acetyl-CoA Carboxylases (ACCs) are key rate-limiting enzymes involved in fatty acid metabolism regulation by catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. Previously, most studies focused on the role of ACC1 in fatty acid metabolism in cancer, while the function of ACC2 remains largely uncharacterized in human cancers, especially in ovarian cancer (OC). Here, we show that ACC2 was significantly downregulated in cancerous tissue of OC, and the downregulation of ACC2 is closely associated with lager tumor size, metastases and worse prognosis in OC patients. Downregulation of ACC2 promoted proliferation and metastasis of OC both in vitro and in vivo by enhancing FAO. Notably, mitochondria-associated ubiquitin ligase (MARCH5) was identified to interact with and downregulate ACC2 by ubiquitination and degradation in OC. Moreover, ACC2 downregulation-enhanced FAO contributed to the progression of OC promoted by MARCH5. In conclusion, our findings demonstrate that MARCH5-mediated downregulation of ACC2 promotes FAO and tumorigenesis in OC, suggesting MARCH5-ACC2 axis as a potent candidate for the treatment and prevention of OC.

Median arcuate ligament syndrome complicated with gallbladder stones: A case report.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare disease caused by compression of the celiac trunk artery by the median arcuate ligament (MAL). It can cause symptoms of postprandial abdominal pain, weight loss, and nausea and vomiting. CASE SUMMARY: A 55-year-old woman was admitted due to abdominal pain, nausea and vomiting. On admission, the patient presented with epigastric pain that worsened after eating, without signs of peritoneal irritation. Computed tomography angiography of the upper abdomen showed compression of the proximal segment of the abdominal trunk, local luminal stenosis with angular "fishhook" changes, which changed significantly during forceful inspiration and expiration; gallbladder stones; and multiple cysts in the liver. Abdominal duplex ultrasonography showed that peak systolic velocity was 352 cm/s. After diagnosis of MALS was confirmed, an arch ligament release procedure was performed. MALS has no specific symptoms and can be misdiagnosed as other abdominal diseases. Awareness of MALS should be improved to avoid misdiagnosis. The commonly used treatment option is MAL release and resection of the peripheral ganglion of the celiac trunk artery. CONCLUSION: The diagnosis and treatment of MALS must be individualized, and MAL release is effective and provides immediate symptomatic relief.

Central retinal vein occlusion with moyamoya disease: a case report.

Moyamoya disease is mainly caused by stenosis or occlusion of the terminal internal carotid artery, anterior cerebral artery, and proximal middle cerebral artery, and an abnormal vascular network is formed near the stenosis or occlusion of vascular lesions. Moyamoya disease can lead to a series of complications such as transient cerebral ischemia, cerebral infarction, and cerebral hemorrhage, which have been reported in the literature. Eye involvement with moyamoya disease is relatively rare in the literature. This article introduces a case of central retinal vein occlusion in a teenager related to moyamoya disease. The patient was only 16 years old and suddenly suffered from vision loss in the left eye. After detailed ophthalmological examination, she was diagnosed with central retinal vein occlusion in the left eye. In order to find the exact cause, we conducted head and neck CTA and brain DSA examinations on the patient, and finally found that the main cause of central retinal vein occlusion in this patient was moyamoya disease, which indicated that central retinal vein occlusion in young people may be caused by moyamoya disease in the early stage. This discovery has great clinical significance, for characteristic manifestations of the eye, suggesting that examination of moyamoya disease is a routine item for such patients, so as to achieve early detection, early diagnosis and early treatment, in order to avoid cerebral infarction, cerebral palsy, and serious or even life-threatening complications such as bleeding.

Risk factors and prognosis of liver metastasis in gallbladder cancer patients: A SEER-based study.

Background: Liver metastasis is a common complication in gallbladder cancer (GBC). We design this study to develop models for predicting the development of liver metastasis in GBC patients and evaluate the risk of mortality in these patients with liver metastasis. Methods: GBC patients from Surveillance Epidemiology and End Results (SEER) between 2010 and 2016 were included in this study. Logistic regression was performed to discover risk factors and construct predictive models for liver metastasis in GBC patients. Cox regression was utilized to find risk factors of mortality in GBC patients with liver metastasis. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the performance of the constructed predictive models. Results: Multivariate logistic regression confirmed that T stage, N stage, and tumor grade were risk factors for liver metastasis in GBC patients. Composed of these factors, the model for predicting the development of liver metastasis had AUCs of 0.707 and 0.657 in the training cohort and testing cohort, respectively. Multivariate Cox regression showed that surgery of the primary site and chemotherapy were independently associated with the mortality of GBC patients with liver metastasis. Composed of these two factors, the predictive model for 1-year mortality of GBC patients with liver metastasis had AUCs of 0.734 and 0.776 in the training cohort and testing cohort, respectively. Conclusion: The predictive models that we constructed are helpful for surgeons to evaluate the risk of liver metastasis in GBC patients and the survival condition of those with liver metastasis. Surgery of the primary site and chemotherapy should be provided for GBC with liver metastasis.

Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway.

Hepatocellular carcinoma (HCC) still presents poor prognosis with high mortality rate, despite of the improvement in the management. The challenge for precision treatment was due to the fact that little targeted therapeutics are available for HCC. Recent studies show that metabolic and circulating peptides serve as endogenous switches for correcting aberrant cellular plasticity. Here we explored the antitumor activity of low molecular components in human umbilical serum and identified a high abundance peptide VI-13 by peptidome analysis, which was recognized as the part of glutamyltransferase signal peptide. We modified VI-13 by inserting four arginines and obtained an analog peptide VI-17 to improve its solubility. Our analyses showed that the peptide VI-17 induced rapid context-dependent cell death, and exhibited a higher sensitivity on hepatoma cells, which is attenuated by polyethylene glycol but not necrotic inhibitors such as z-VAD-fmk or necrostatin-1. Morphologically, VI-17 induced cell swelling, blebbing and membrane rupture with release of cellular ATP and LDH into extracellular media, which is hallmark of oncotic process. Mechanistically, VI-17 induced cell membrane pore formation, degradation of α-tubulin via influx of calcium ion. These results indicated that the novel peptide VI-17 induced oncosis in HCC cells, which could serve as a promising lead for development of therapeutic intervention of HCC.

Dynamics and controllability of droplet fusion under gas-liquid-liquid three-phase flow in a microfluidic reactor.

Gas-liquid-liquid three-phase flow systems have unique advantages of controlling reagent manipulation and improving reaction performance. However, there remains a lack of insight into the dynamics and controllability of water droplet fusion assisted by gas bubbles, particularly scaling laws for use in the design and operation of complex multiphase flow processes. In the present work, a microfluidic reactor with three T-junctions was employed to sequentially generate gas bubbles and then fuse two dispersed water droplets. The formation of the dispersed phase was divided into multiple stages, and the bubble/droplet size was correlated with operating parameters. The formation of the second dispersed droplet at the third T-junction was accompanied by the fusion of the two dispersed water droplets that were formed. It revealed a two-stage process (i.e. drainage and fusion) for the two droplets to fuse while becoming mature by breaking-up with the secondary water supply stream. In addition, a droplet contact model was employed to understand the influence on the process stability and uniformity of the merged/fused droplets by varying the surfactant concentration (in oil), the viscosity of the water phase, and the flow rates of different fluids. The study provides a deeper understanding of the droplet fusion characteristics on gas-liquid-liquid three-phase flow in microreactors for a wide range of applications.

Cryo-EM structure of the RC-LH core complex from an early branching photosynthetic prokaryote.

Photosynthetic prokaryotes evolved diverse light-harvesting (LH) antennas to absorb sunlight and transfer energy to reaction centers (RC). The filamentous anoxygenic phototrophs (FAPs) are important early branching photosynthetic bacteria in understanding the origin and evolution of photosynthesis. How their photosynthetic machinery assembles for efficient energy transfer is yet to be elucidated. Here, we report the 4.1 Å structure of photosynthetic core complex from Roseiflexus castenholzii by cryo-electron microscopy. The RC-LH complex has a tetra-heme cytochrome c bound RC encompassed by an elliptical LH ring that is assembled from 15 LHαß subunits. An N-terminal transmembrane helix of cytochrome c inserts into the LH ring, not only yielding a tightly bound cytochrome c for rapid electron transfer, but also opening a slit in the LH ring, which is further flanked by a transmembrane helix from a newly discovered subunit X. These structural features suggest an unusual quinone exchange model of prokaryotic photosynthetic machinery.