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关键词： Ricci semi-symmetric   A-isotropic   A-principal   Kahler structure   Complex conjugation   Complex quadric  

摘要： First we introduce the notion of Ricci semi-symmetric real hypersurfaces in the complex quadric Q(m) = SOm+2/SOmSO2 and show that the unit normal vector field N is singular. Next we give a new classification of real hypersurfaces in the complex quadric Q(m) = SOm+2/SOmSO2 with semi-symmetric Ricci tensor. (C) 2021 Elsevier B.V. All rights reserved.

关键词： Kidney   Oncocytic renal cell carcinoma   Papillary   Unclassified   Copy number variation pattern   Oncocytoma   Overlapping  

摘要： So-called oncocytic papillary renal cell carcinoma (OPRCC) is a poorly defined variant of papillary renal cell carcinoma. Since its first description, several studies were published with conflicting results, and thus precise definition is lacking. A cohort of 39 PRCCs composed of oncocytic cells were analyzed. Cases were divided into 3 groups based on copy number variation (CNV) pattern. The first group consisted of 23 cases with CNV equal to renal oncocytoma. The second group consisted of 7 cases with polysomy of chromosomes 7 and 17 and the last group of 9 cases included those with variable CNV. Epidemiologic, morphologic and immunohistochemical features varied among the groups. There were not any particular histomorphologic features correlating with any of the genetic subgroups. Further, a combination of morphologic, immunohistochemical, and molecular-genetic features did not allow to precisely predict biologic behavior. Owing to variable CNV pattern in OPRCC, strict adherence to morphology and immunohistochemical profile is recommended, particularly in limited samples (i.e., core biopsy). Applying CNV pattern as a part of a diagnostic algorithm can be potentially misleading. OPRCC is a highly variable group of tumors, which might be misdiagnosed as renal oncocytoma. Using the term OPRCC as a distinct diagnostic entity is, thanks to its high heterogeneity, questionable.

关键词： KIT   Lung cancer   Thymic carcinoma   Tuft cells  

摘要： Introduction: In-depth genomic characterization of thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas (TCs), failed to identify targetable mutations and suggested unique biology of TETs, including KIT expression in most TCs. Recently, tuft cell-like medullary thymic epithelial cells were identified in the murine thymus, and our reanalysis of the published gene expression data revealed that these cells express KIT. In addition, recently, a minor subset of SCLCs with tuft cell-like features was described. Methods: We interrogated mRNA expression data from our tumor cohorts (N = 60) and publicly available, independent data sets from TETs and NSCLC (N = 1199) for expression of tuft cell genes and KIT. Expression of KIT and of POU2F3 protein, the master regulator of tuft cells, was analyzed in cancer tissue (N = 344) by immunohistochemistry. Results: Normal human thymic tuft cells and most TCs coexpressed KIT and known tuft cell genes, particularly POU2F3 and GFI1B. Unexpectedly, small subsets of tuft cell- like tumors coexpressing POU2F3, GFI1B, and KIT werealso identified among pulmonary squamous cell carcinomas, adenocarcinomas, and large cell neuroendocrine carcinoma and clustered together in each histologic cohort. In addition to the tuft cell-like signature, both thymic and lung tuft cell-like carcinomas had distinct genetic, pathologic, and clinical features in each cohort. Conclusions: We suggest that the tuft cell-like phenotype defines novel subsets of thymic and pulmonary carcinoma. Its high prevalence in thymic squamous cell carcinomas that have no known toxic or viral etiologies suggests a new mechanism of carcinogenesis that may lead to specific drug susceptibilities. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

关键词： SARS-CoV-2   complement   anaphylatoxin receptors   primary human airway epithelial cells  

摘要： Background: Excessive inflammation triggered by a hitherto undescribed mechanism is a hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and is associated with enhanced pathogenicity and mortality. Objective: Complement hyperactivation promotes lung injury and was observed in patients suffering from Middle East respiratory syndrome-related coronavirus, SARS-CoV-1, and SARS-CoV-2 infections. Therefore, we investigated the very first interactions of primary human airway epithelial cells on exposure to SARS-CoV-2 in terms of complement component 3 (C3)-mediated effects. Methods: For this, we used highly differentiated primary human 3-dimensional tissue models infected with SARS-CoV-2 patient isolates. On infection, viral load, viral infectivity, intracellular complement activation, inflammatory mechanisms, and tissue destruction were analyzed by real-time RT-PCR, high content screening, plaque assays, luminex analyses, and transepithelial electrical resistance measurements. Results: Here, we show that primary normal human bronchial and small airway epithelial cells respond to SARS-CoV-2 infection by an inflated local C3 mobilization. SARS-CoV-2 infection resulted in exaggerated intracellular complement activation and destruction of the epithelial integrity in monolayer cultures of primary human airway cells and highly differentiated, pseudostratified, mucus-producing, ciliated respiratory tissue models. SARS-CoV-2-infected 3-dimensional cultures secreted significantly higher levels of C3a and the proinflammatory cytokines IL-6, monocyte chemoattractant protein 1, IL-1a, and RANTES. Conclusions: Crucially, we illustrate here for the first time that targeting the anaphylotoxin receptors C3a receptor and C5a receptor in nonimmune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.

摘要： Background For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. Objectives To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology. Methods We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. Results Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%;24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%;10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years. Conclusions 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.

关键词： CD30-positive T cell lymphoproliferative disorder   Extranodal NK/T-cell lymphoma   Gamma-delta T-cell lymphoid proliferations of the skin   Hydroa vacciniforme-like lymphoproliferative disorder   Lymphomatoid papulosis type D   Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma   Primary cutaneous γδ T-cell lymphoma   Subcutaneous panniculitis-like T-cell lymphoma  

摘要： Primary cutaneous T-cell lymphomas pose a diagnostic challenge for dermatopathologists, hematopathologists, and general surgical pathologists. Recognition of gamma/delta phenotype in cutaneous T proliferations has been enhanced by the availability of antibodies against TCRgamma and delta for immunohistochemistry. Thus, reporting gamma/delta phenotype in a cutaneous T-cell lymphoid proliferation may indicate a significant change in therapy and a challenge for dermatologists and oncologists who treat these patients. Herein, we discuss primary cutaneous gamma/delta T-cell lymphoma, its differential diagnosis, and other skin lymphoid proliferations that may show gamma/delta phenotype. Awareness of the occurrence of gamma/delta phenotype in both T-cell lymphomas and benign lymphoid proliferations involving skin is crucial for a better interpretation of histopathologic findings. Integration of clinical presentation, morphology, immunoprofile, and molecular findings is key for a correct diagnosis and appropriate therapy of lesions displaying gamma/delta T-cell phenotype.

关键词： alectinib   ALK rearrangement   crizotinib   non‐   small cell lung cancer   STRN‐   ALK  

摘要： Anaplastic lymphoma kinase (ALK) rearrangements are drivers of a subset of non-small cell lung cancer (NSCLC). The rapid progression of ALK inhibitors has significantly prolonged the progression-free survival of patients with ALK gene-sensitive mutations. However, the response of patients with rare ALK rearrangements to tyrosine kinase inhibitors remains unknown. Here, we report a rare case of striatin (STRN)-ALK-positive NSCLC showing primary resistance to first-line therapy alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting.

关键词： AscH2   Bactericidal activity   Primary human umbilical vein endothelial cells   HUVEC survival and function   Immunomodulatory effect   S   aureus infection  

摘要： Background: Vitamin C (ascorbic acid, AscH2) has been shown to enhance immunity. Here, we studied its immunomodulatory effect on human endothelial cells (ECs) during S. aureus infection. Materials and methods: The ex vivo effects of AscH2 were performed on primary human umbilical vein endothelial cells (HUVECs) infected or not with S. aureus. Results: AscH2 treatment induced a marked downregulation of nitric oxide (NO) production and a moderate upregulation of arginase activity in S. aureus-infected HUVECs (respectively, p < 0.05 and p > 0.05). Although the upregulated release levels of soluble intercellular adhesion molecular 1 (sICAM-1/sCD54) and sE-selectin (sCD62E) molecules were not significantly different between treated and untreated S. aureus-infected HUVECs, AscH2 treatment induced reversing effect on sICAM-1 release when comparing to uninfected control HUVECs. Moreover, AscH2 treatment appears to have a significant effect on preventing HUVEC necrosis induced by S. aureus infection (p < 0.05). Furthermore, AscH2 treatment induced a significant upregulation of cell protective redox biomarker in S. aureus-infected, as shown by superoxide dismutase (SOD) activity (p < 0.05), but not by catalase activity (p > 0.05). Additionally, S. aureus infection markedly downregulated total bound calcium ions (bCa2+) levels as compared to control HUVECs, whereas, AscH2 treatment induced a slight upregulation of bCa2+ levels in infected HUVECs as compared to infected and untreated HUVECs (p > 0.05). On the other hand, AscH2 treatment downregulated increased total cellular cholesterol content (tccCHOL) levels in HUVECs induced by S. aureus infection (p < 0.05). In addition, AscH2 treatment markedly reversed S. aureus effect on upregulation of intracellular glucose (iGLU) levels within infected HUVECs (p < 0.05). Moreover, AscH2 treatment significantly downregulated S. aureus growth (p < 0.05), and significantly upregulated bacterial internalization and intracellular killing b

关键词： Pre-chamber combustion   Lean combustion   Pre-chamber jet speed   Planar laser-induced fluorescence   OH* chemiluminescence  

摘要： We studied the relationship between pre-chamber jet and main chamber ignition in the pre-chamber combustion (PCC) of an optical engine, fueled with methane and equipped with an active pre-chamber with two rows of orifices. Acetone planar laser-induced fluorescence (PLIF) and OH* chemiluminescence imaging techniques were simultaneously applied to visualize the pre-chamber jet and the reaction zone in the main chamber, respectively. The pre-chamber fueling was constant and the main chamber fueling was increased to form an ultra-lean case and a lean case with global excess air ratios (lambda) of 2.3 and 1.8, respectively. Results indicate that a higher pressure difference between pre-chamber and main chamber (AP) produces larger pre-chamber jet penetration speed;the maximum pre-chamber jet penetration speed appears at timing around the peak AP. Over enrichment of the pre-chamber charge reduces the peak AP and thus does not favor a faster pre-chamber jet discharge. In addition to the main pre-chamber jet, a weaker post jet discharge process is visualized;the former is due to the pre-chamber combustion while the latter due to the AP fluctuation and the cylinder volume expansion. The post pre-chamber jet is accompanied by a post reaction zone in the ultra-lean case (lambda= 2.3) and there are two unburned regions in the main chamber: one is around the pre-chamber nozzle and the other between the adjacent reaction zones. These two unburned regions are consumed by flame propagation in the lean case (lambda= 1.8). The weak pre-chamber jet from the upper-row orifice does not produce any distinct reaction zone, indicating that the pre-chamber orifice location and arrangement on the nozzle also matters in the pre-chamber design. The pre-chamber jet penetration length is longer than that of the reaction zone during pre-chamber discharge;the penetration length difference between the pre-chamber jet and reaction zone decreases with increasing main chamber fueling. (C) 2021 The Com

关键词： Thoracic aorta   Hypertension   Stress fiber   Mechanotransduction   Principal direction   Photobleaching  

摘要： Stress fibers (SFs) in cells transmit external forces to cell nuclei, altering the DNA structure, gene expression, and cell activity. To determine whether SFs are involved in mechanosignal transduction upon intraluminal pressure, this study investigated the SF direction in smooth muscle cells (SMCs) in aortic tissue and strain in the SF direction. Aortic tissues were fixed under physiological pressure of 120 mmHg. First, we observed fluorescently labeled SFs using two-photon microscopy. It was revealed that SFs in the same smooth muscle layers were aligned in almost the same direction, and the absolute value of the alignment angle from the circumferential direction was 16.8 degrees +/- 5.2 degrees (n = 96, mean +/- SD). Second, we quantified the strain field in the aortic tissue in reference to photo-bleached markers. It was found in the radial-circumferential plane that the largest strain direction was - 21.3 degrees +/- 11.1 degrees, and the zero normal strain direction was 28.1 degrees +/- 10.2 degrees. Thus, the SFs in aortic SMCs were not in line with neither the largest strain direction nor the zero strain direction, although their orientation was relatively close to the zero strain direction. These results suggest that SFs in aortic SMCs undergo stretch, but not maximal and transmit the force to nuclei under intraluminal pressure.