Background Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) have been published. However, mortality and morbidity analyses, important for better understanding the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. Methods The cohort consisted of 11 male and 3 female patients, with 9 patients aged 70 years or above, and nearly all had underlying diseases. Results Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest computed tomography scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, this cohort had high level of cytokines such as interleukin-6 in all 8 patients tested. Conclusions The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models and will be of help in understanding the pathogenesis of this disease.

A small, multigene family encodes 4-coumarate:CoA ligases (4CLs) that catalyze the ligation of CoA to hydroxycinnamic acids, a branch point directing metabolites to flavonoid or monolignol pathways. In this study, we characterized four 4CL genes from M. notabilis Genome Database, and cloned four Ma4CL genes from M. atropurpurea cv. Jialing No.40. A tissue-specific expression analysis indicated that Ma4CL3 was expressed at higher levels than the other genes, and that Ma4CL3 was strongly expressed in root bark, stem bark, and old leaves. Additionally, the expression pattern of Ma4CL3 was similar to the trend of the total flavonoid content throughout fruit development. A phylogenetic analysis suggested that Mn4CL1, Mn4CL2, and Mn4CL4 belong to class I 4CLs, and Mn4CL3 belongs to class II 4CLs. Ma4CL genes responded differently to a series of stresses. Ma4CL3 expression was higher than that of the other Ma4CL genes following wounding, salicylic acid, and ultraviolet treatments. An in vitro enzyme assay indicated that 4-coumarate acid was the best substrate among cinnamic acid, 4-coumarate acid, and caffeate acid, but no catalytic activity to sinapate acid and ferulate acid. The results of subcellular localization experiments showed that Ma4CL3 localized to the cytomembrane, where it activated transcription. We used different vectors and strategies to fuse Ma4CL3 with stilbene synthase (STS) to construct four Ma4CL-MaSTS co-expression systems to generate resveratrol. The results indicated that only a transcriptional fusion vector, pET-Ma4CL3-T-MaSTS, which utilized a T7 promoter and lac operator for the expression of MaSTS, could synthesize resveratrol.

Epilepsy is one of the most common symptoms of many neurological disorders. The typical excessive, synchronous and aberrant firing of neurons originating from different cerebral areas cause spontaneous recurrent epileptic seizures. Prolonged epilepsy can lead to neuronal damage and cell death. The mechanisms underlying epileptic pathogenesis and neuronal death remain unclear. Ferroptosis is a newly defined form of regulated cell death that is characterized by the overload of intracellular iron ions, leading to the accumulation of lethal lipid-based reactive oxygen species (ROS). To date, studies have mainly focused on its role in tumors and various neurological disorders, including epilepsy. Current research shows that inhibition of ferroptosis is likely to be an effective therapeutic approach for epilepsy. In this review, we outline the pathogenesis of ferroptosis, regulatory mechanisms of ferroptosis, related regulatory molecules, and their effects on epilepsy, providing a new direction for discovering new therapeutic targets in epilepsy.

BACKGROUND Lower grade gliomas (LGG) are heterogenous diseases by clinical, histological, and molecular criteria. We aimed to personalize the diagnosis and therapy of LGG patients by developing and validating robust cellular morphometric subtypes (CMS) and to uncover the molecular signatures underlying these subtypes. METHODS Cellular morphometric biomarkers (CMBs) were identified with artificial intelligence technique from TCGA-LGG cohort. Consensus clustering was used to define CMS. Survival analysis was performed to assess the clinical impact of CMBs and CMS. A nomogram was constructed to predict 3- and 5- year overall survival (OS) of LGG patients. Tumor mutational burden (TMB), and immune cell infiltration between subtypes were analyzed using the Mann-Whitney test. The double-blinded validation for important immunotherapy-related biomarkers were executed using immunohistochemistry (IHC). RESULTS We developed a machine learning pipeline to extract CMBs from whole slide images of tissue histology; identifying and externally validating robust CMS of LGGs in multi-center cohorts. The subtypes had independent predicted OS across all three independent cohorts. In the TCGA-LGG cohort, patients within the poor-prognosis subtype responded poorly to primary and follow-up therapies. LGGs within the poor-prognosis subtype were characterized by high mutational burden, high frequencies of copy number alterations, and high levels of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher levels of PD-1/PD-L1/CTLA-4 were confirmed by immunohistochemical staining. In addition, the subtypes learned from LGG demonstrates translational impact on glioblastoma (GBM). CONCLUSIONS We developed and validated a framework (CMS-ML) for CMS discovery in LGG associated with specific molecular alterations, immune micro-environment, prognosis, and treatment response.

Hypogastric approach is as effective and safe as VEIL-L for penile cancer. Moreover, VEIL-H can avoid the operation on both the limb and abdomen if laparoscopic pelvic lymphadenectomy is required.