FOXA3 promotes the occurrence and development of HB by up-regulating AFP and HNF1A/MYC expression, and down-regulating ZFHX3 expression.Autophagy is a lysosome-dependent degradation pathway essential to maintain cellular homeostasis. Therefore, either defective or excessive autophagy may be detrimental for cells and tissues. The past decade was characterized by significant advances in molecular dissection of stimulatory autophagy inputs; however, our understanding of the mechanisms that restrain autophagy is far from complete. Here, we describe a negative feedback mechanism that limits autophagosome biogenesis based on the selective autophagy-mediated degradation of ATG13, a component of the ULK1 autophagy initiation complex. We demonstrate that the centrosomal protein OFD1 acts as bona fide autophagy receptor for ATG13 via direct interaction with the Atg8/LC3/GABARAP family of proteins. We also show that patients with Oral-Facial-Digital type I syndrome, caused by mutations in the OFD1 gene, display excessive autophagy and that genetic inhibition of autophagy in a mouse model of the disease, significantly ameliorates polycystic kidney, a clinical manifestation of the disorder. Selleck bpV Collectively, our data report the discovery of an autophagy self-regulated mechanism and implicate dysregulated autophagy in the pathogenesis of renal cystic disease in mammals.

In the 8th edition American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system (TNM-8), changes have been made regarding anaplastic thyroid carcinoma (ATC) compared with the 7th edition (TNM-7). The major changes are that anaplastic ATC now has the same T stage definitions as differentiated thyroid cancer, and new staging of IVA and IVB is implemented. However, the clinical impact of the new edition for ATC remains unclear due to scarce and conflicting data. In this study, we compared the AJCC TNM-7 and TNM-8 in the same group of patients.

In this retrospective study, we included patients who were diagnosed with ATC between 2004 and 2015; data were gathered from the Surveillance, Epidemiology and End Results (SEER) database.

Overall survival (OS) was evaluated according to T stage and TNM stage according to the 7th and 8th editions. Kaplan-Meier and log-rank testing was used to analyse OS. The effect of potential predictors was estimated using the Cox regression model.

We included 669 patients in the study. The median age of the cohort was 70years. During the follow-up, 600 (89.7%) patients died, 528 of whom died of thyroid cancer. The TNM-8 T staging more effectively predicted survival than the 7th edition (proportion of variation explained 3.53% vs. 1.72%). However, the clinical stage was almost unchanged according to the TNM-8 (proportion of variation explained 10.69% vs. 10.73%).

The new T classification is an effective predictor of survival for patients with ATC. The results support the use of T definitions as per those of differentiated thyroid cancer. However, whether lymph node metastasis should be taken into account for defining ATC TNM staging should be reconsidered.

The new T classification is an effective predictor of survival for patients with ATC. The results support the use of T definitions as per those of differentiated thyroid cancer. However, whether lymph node metastasis should be taken into account for defining ATC TNM staging should be reconsidered.An 18-year-old man presented to our hospital with muscular pain, diffuse petechiae, spontaneous thigh ecchymosis, edema and pain of the right knee, bilateral pretibial subcutaneous nodules, and gingival hypertrophy and hemorrhage. His history was positive for a mixed anxiety-depressive disorder and a restrictive diet caused by self-diagnosed food allergies. Skin lesions appeared like hyperkeratotic papules with coiled hairs and perifollicular hemorrhages. A diagnosis of scurvy was made upon demonstration of low serum levels of ascorbic acid. An allergy evaluation found cross-reactivity between pollens and food, related to the presence of panallergens. Moreover, we found that our patient was also affected by celiac disease. In conclusion, scurvy should be considered in the differential diagnosis of patients with petechiae and ecchymosis, especially when food restriction, malabsorption, or psychiatric disorders are present.We studied urinary bladders of adult male and female Xenopus laevis using light microscopy of stained tissue sections and scanning electron microscopy (SEM) of vascular corrosion casts (VCCs). Results showed that bilaterally a vesical artery branched off the femoral artery. At the dorso-lateral serosal surface of the body of the bladder each artery splitted within a short distance into up to five smaller arteries that supplied body and neck regions. Arteries gave off short and long terminal arterioles, which fed the mucosal capillary meshwork. Long terminal arterioles followed dimensional changes of the bladder, while short ones anchored the capillary network to the arterial system. Capillary mesh sizes and shapes varied according to the filling state of the urinary bladder. In the highly to moderately distended (filled) bladder, capillaries were rather straight or undulated only slightly, in the contracted (emptied) bladder they undulated strongly and lay side by side. Postcapillary venules formed by two equally sized capillaries or from capillaries, which serially drained into a small postcapillary venule. Vesical venules formed a large dorsal vesical and a varying number of smaller lateral and ventral vesical veins. The dorsal vesical vein drained either directly or via the posterior hemorrhoidal vein into the common pelvic vein. Lateral and ventral vesical veins also drained into the latter. The vascular patterns found were discussed in respect to the bladder spatial movements during distention (filling) and relaxation (emptying). Furthermore, it was hypothesized that an extensively filled bladder could compress the overlaying abdominal vein forcing part of the blood otherwise drained towards the liver to be detoured via the renal portal veins to the kidneys.The aim was to retrospectively evaluate our experience in a large series of patients affected by isolated congenital ventral penile curvature, surgically treated using a previously described modified incisional corporoplasty. Two hundred and six patients with isolated congenital ventral penile curvature underwent a modified incisional corporoplasty. Mean age at surgery was 20.7 ± 5.5 years, and degree of ventral curvature was 60 ± 23°. After the point of maximum convexity identification, Buck’s fascia was vertically opened along the deep dorsal vein, which was partially ligated, resected and removed. Tunica albuginea was then longitudinally incised and transversally closed. Post-operative follow-up examination was performed at 2 weeks, 6, 12 and 24 months and then annually. Surgical time was 79 ± 12 min. At follow-up, 189 out of 198 patients (95%) were completely satisfied, four patients (2%) complained a recurrence of penile curvature, and 6 (3%) complained about shortening of the penis. None of the patients had any interference with sexual activity.