SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Well-differentiated, pedunculated liposarcoma of the hypopharynx

Introduction: Liposarcoma of the hypopharynx is extremely rare, as only 28 cases have been reported in the literature. The cardinal symptom of liposarcoma is progressively worsening dysphagia. Case report: The authors report the case of a 71-year-old man who presented with dysphagia, marked weight loss over several weeks and an episode of exteriorization of a solid mass from the mouth during an episode of vomiting. Imaging revealed a fat density intra-oesophageal mass. Panendoscopy and upper gastrointestinal endoscopy visualized the pedunculated tumour in the left piriform sinus, which was able to be exteriorized via the mouth. The tumour was then resected endoscopically at its hypopharyngeal insertion pedicle. Histological examination of the operative specimen concluded on well-differentiated benign liposarcoma. Discussion: Well-differentiated liposarcoma is the most common form of liposarcoma, but is only exceptionally reported in the hypopharynx. The main symptoms are related to compression of adjacent structures. Imaging findings are nonspecific. Only histological examination can distinguish liposarcoma from other benign oesophageal tumours. Standard treatment consists of wide, complete resection, which is not always possible in the neck. Long-term follow-up of these patients is essential in order to rapidly detect recurrence

Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A

Oxazolidinones represent a new and promising class of antibacterial agents. Current, research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Many oxazolidinones, including linezolid (marketed as 2 Zyvox), are inhibitors of monoamine oxidase A (MAO-A), which presents an undesired side effect. Recently, it was found that the 1,2,3-triazole is a good replacement for the conventional acetamide functionality found in oxazolidinones. We now disclose the finding that 1,2.3-triazoles bearing, a substituent like methyl, small substituted methyl, bromo, or a linear (sp-hybridized) group at the 4 position (compounds such as 5, 16, 19, and 21) are good antibacterials with reduced or no activity.. within the detection limit of the assay, against MAO-A. The results are especially promising for the development of oxazolidinones with an improved safety profile. The MAO-A SAR can be rationalized on the basis of docking studies to a MAO-A/MAO-B homolog; model.</p