LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism.

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.

Cervical spondylotic myelopathy with syringomyelia presenting as hip Charcot neuroarthropathy: A case report and review of literature.

BACKGROUND: Charcot neuroarthropathy (CN) is a systemic disease characterized by progressive bone loss and destruction, which is usually closely related to diabetes, HIV, etc. However, CN caused by syringomyelia accounts for only 5% of CN cases; the shoulder and elbow are most often involved, and the hip joint is rarely affected. As a rare factor, cervical spondylotic myelopathy (CSM) can be associated with syringomyelia, which is scarcely reported in the literature. Here, we present the first case report to date of CN of the hip caused by syringomyelia secondary to CSM. CASE SUMMARY: We describe a 76-year-old male patient who was diagnosed with CSM due to neck pain and weakness of limbs 16 years ago. Four years ago, he noticed recurrent swelling of the right hip with pain and was diagnosed with degenerative arthritis. Recently, however, his symptoms gradually worsened, and because of progressive pain, destabilization and weakness of the right hip, he was admitted to our hospital. Through systematic physical, radiographic and laboratory examinations, we finally reached a diagnosis: CN of the right hip associated with syringomyelia secondary to CSM. After comprehensive evaluation of the patient's condition, we performed right total hip arthroplasty. During the follow-up, the patient felt well clinically and could walk independently with a knee brace. CONCLUSION: We suggest a possible etiological association between CSM and syringomyelia, which may reflect a potential pathogenesis of CN. We encourage clinicians to actively carry out a detailed medical history and comprehensive physical and imaging examinations in patients with joint lesions, especially chronic shoulder neck pain, to rule out the possibility of this association, which plays a crucial role in the early diagnosis of CN. Arthroplasty may no longer be an absolute contraindication to surgical treatment of CN. Reasonable selection of the surgical strategy can markedly improve the clinical symptoms and quality of life of patients.

A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Migration of hem-o-lock clips and stitches into the duodenum after laparoscopic hepatectomy and cholecystectomy: A case report.

RATIONALE: Migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy is incredibly rare with a poorly understood mechanism. PATIENT CONCERNS: A 56-year-old woman who underwent laparoscopic left hepatectomy and cholecystectomy in August 2016 was admitted to our hospital with nausea and vomiting in December 2017. DIAGNOSES: Abdominal computed tomography (CT) scan showed high density shades in duodenal ampulla. Esophagogastroduodenoscopy showed deformation of the duodenal ampulla into two lumens; hem-o-lock clips and stitches were detected in the upper lumen. Contrast enhanced CT scan revealed gastric cancer with liver metastasis (GCLM). INTERVENTIONS: The hem-o-lock clips and stitches were present in the wall of the duodenum; therefore, no attempt was made to remove them. High quality liquid diet, partial parenteral nutrition, and chemotherapy were administered to the patient. OUTCOMES: In September 2018, the patient died of hepatic failure caused by GCLM. LESSONS: This rare complication of the migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy can cause epigastric pain and duodenal obstruction. The complication could be potentially avoided using absorbable endoclips and stitches or by performing of ultrasonic dissection by a skilled operator.

Experiments of a 100 kV-level pulse generator based on metal-oxide varistor.

This paper introduces the development and experiments of a 100 kV-level pulse generator based on a metal-oxide varistor (MOV). MOV has a high energy handling capacity and nonlinear voltage-current (V-I) characteristics, which makes it useful for high voltage pulse shaping. Circuit simulations based on the measured voltage-current characteristics of MOV verified the shaping concept and showed that a circuit containing a two-section pulse forming network (PFN) will result in better defined square pulse than a simple L-C discharging circuit. A reduced-scale experiment was carried out and the result agreed well with simulation prediction. Then a 100 kV-level pulse generator with multiple MOVs in a stack and a two-section pulse forming network (PFN) was experimented. A pulse with a voltage amplitude of 90 kV, rise time of about 50 ns, pulse width of 500 ns, and flat top of about 400 ns was obtained with a water dummy load of 50 Ω. The results reveal that the combination of PFN and MOV is a practical way to generate high voltage pulses with better flat top waveforms, and the load voltage is stable even if the load's impedance varies. Such pulse generator can be applied in many fields such as surface treatment, corona plasma generation, industrial dedusting, and medical disinfection.