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Lanthionine synthase from the oral bacterium Fusobacterium nucleatum is a fold type II pyridoxal-5′-phosphate (PLP)-dependent enzyme that catalyzes the β-replacement of l-cysteine by a second molecule of l-cysteine to form H2S and l-lanthionine. The meso-isomer of the latter product is incorporated into the F. nucleatum peptidoglycan layer. Herein, we investigated the catalytic role of S224, which engages in hydrogen-bond contact with the terminal carboxylate of l-lanthionine in the closed conformation of the enzyme. Unexpectedly, the S224A variant elicited a 7-fold increase in the turnover rate for H2S and lanthionine formation and a 70-fold faster rate constant for the formation of the α-aminoacrylate intermediate compared to the wild-type enzyme. Presteady state kinetic analysis further showed that the reaction between S224A and l-cysteine leads to the formation of the more reactive ketoenamine tautomer of the α-aminoacrylate. The α-aminoacrylate with the protonated Schiff base is not an observable intermediate in the analogous reaction with the wild type, which may account for its attenuated kinetic properties. However, the S224A substitution is detrimental to other aspects of the catalytic cycle; it facilitates the α,β-elimination of l-lanthionine, and it weakens the enzyme’s catalytic preference for the formation of l-lanthionine over that of l-cystathionine.The first example of the oxidative addition of a C(sp3)-F bond in trifluoromethylarenes to a nickel(0) complex is described. A nickel(0) complex that bears two N-heterocyclic carbene (NHC) ligands of low steric demand is able to cleave C(sp3)-F bonds of trifluoromethylarenes to afford the corresponding trans-difluorobenzyl nickel(II) fluoride complexes. Isolation and characterization studies suggested that the cleavage of the C(sp3)-F bond proceeds via an η2-arene nickel(0) complex. Taking advantage of the reactivity of these nickel(II) fluoride complexes, we developed a catalytic hydrodefluorination of trifluoromethylarenes using hydrosilanes. A computational study indicated that the electron-rich nickel(0) center supported by two relatively small NHC ligands cleaves the C(sp3)-F bond via a syn-SN2′ mechanism.While zwitterionic interfaces are known for their excellent low-fouling properties, the underlying molecular principles are still under debate. In particular, the role of the zwitterion orientation at the interface has been discussed recently. For elucidation of the effect of this parameter, self-assembled monolayers (SAMs) on gold were prepared from stoichiometric mixtures of oppositely charged alkyl thiols bearing either a quaternary ammonium or a carboxylate moiety. The alkyl chain length of the cationic component (11-mercaptoundecyl)-N,N,N-trimethylammonium, which controls the distance of the positively charged end group from the substrate’s surface, was kept constant. In contrast, the anionic component and, correspondingly, the distance of the negatively charged carboxylate groups from the surface was varied by changing the alkyl chain length in the thiol molecules from 7 (8-mercaptooctanoic acid) to 11 (12-mercaptododecanoic acid) to 15 (16-mercaptohexadecanoic acid). In this way, the charge neutrality of the coating was maintained, but the charged groups exposed at the interface to water were varied, and thus, the orientation of the dipoles in the SAMs was altered. In model biofouling studies, protein adsorption, diatom accumulation, and the settlement of zoospores were all affected by the altered charge distribution. This demonstrates the importance of the dipole orientation in mixed-charged SAMs for their inertness to nonspecific protein adsorption and the accumulation of marine organisms. Overall, biofouling was lowest when both the anionic and the cationic groups were placed at the same distance from the substrate’s surface.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower than that of SARS and Middle East respiratory syndrome (MERS), the higher transmissibility of SARS-CoV-2 has caused the total fatality to surpass other viral diseases, reaching more than 1 million globally as of October 6, 2020. The rate at which the disease is spreading calls for a therapy that is useful for treating a large population. Multiple intersecting viral and host factor targets involved in the life cycle of the virus are being explored. Because of the frequent mutations, many coronaviruses gain zoonotic potential, which is dependent on the presence of cell receptors and proteases, and therefore the targeting of the viral proteins has some drawbacks, as strain-specific drug resistance can occur. Moreover, the limited number of proteins in a virus makes the number of available targets small. Although SARS-CoV and SARS-CoV-2 share common mechanisms of entry and replication, there are substantial differences in viral proteins such as the spike (S) protein. In contrast, targeting cellular factors may result in a broader range of therapies, reducing the chances of developing drug resistance. In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.

Antiplatelet therapy (APT) after interventions for lower extremity artery disease (LEAD) is recommended. However, (inter)national guidelines vary on type and duration of APT. This report aimed to present the results of a survey on antithrombotic prescribing patterns after lower limb interventions in the Netherlands and an overview of the available literature on this topic.

Vascular surgeons from the Dutch Society for Vascular Surgery and interventional radiologists from the Dutch Society for Interventional Radiology received an online survey on the type and duration of antithrombotic medication after lower limb interventions.

Surveys were completed by 139 of 285 vascular surgeons (49%) and 24 of 288 (8%) interventional radiologists. Clopidogrel was the most prescribed drug after iliac percutaneous transluminal angioplasty (PTA) (77%), femoral PTA (77%), femoral PTA with drug-coated balloon (66%), and femoropopliteal (80%) and femorocrural (51%) prosthetic bypasses. Dual APT (DAPT), consisting of aspiriniable. These results reflect low-level evidence and discrepancy in current guideline recommendations.Around the end of December 2019, a new beta-coronavirus from Wuhan City, Hubei Province, China began to spread rapidly. The new virus, called SARS-CoV-2, which could be transmitted through respiratory droplets, had a range of mild to severe symptoms, from simple cold in some cases to death in others. The disease caused by SARS-CoV-2 was named COVID-19 by WHO and has so far killed more people than SARS and MERS. Following the widespread global outbreak of COVID-19, with more than 132758 confirmed cases and 4955 deaths worldwide, the World Health Organization declared COVID-19 a pandemic disease in January 2020. Earlier studies on viral pneumonia epidemics has shown that pregnant women are at greater risk than others. During pregnancy, the pregnant woman is more prone to infectious diseases. Research on both SARS-CoV and MERS-CoV, which are pathologically similar to SARS-CoV-2, has shown that being infected with these viruses during pregnancy increases the risk of maternal death, stillbirth, intrauterine growth retardation and, preterm delivery. With the exponential increase in cases of COVID-19 throughout the world, there is a need to understand the effects of SARS-CoV-2 on the health of pregnant women, through extrapolation of earlier studies that have been conducted on pregnant women infected with SARS-CoV, and MERS-CoV. There is an urgent need to understand the chance of vertical transmission of SARS-CoV-2 from mother to fetus and the possibility of the virus crossing the placental barrier. Additionally, since some viral diseases and antiviral drugs may have a negative impact on the mother and fetus, in which case, pregnant women need special attention for the prevention, diagnosis, and treatment of COVID-19.The association of small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL) with different malignancies has been reported in the literature. Also the occurrence of a second haematological disease has been described, more frequently as a secondary event in patients receiving chemotherapeutic agents. We report a case of CLL with concurrent acute myeloid leukaemia in an untreated patient, with emphasis on the need of a detailed immunomorphological study to identify the coexistence of the two diseases in the same pathological tissue.The interesting case about a patients with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome due to the variant m.8344A>G with a heteroplasmy rate of 95% reported by Felczak et al. expands the phenotypic spectrum of MERRF syndrome. The authors reported a pituitary adenoma, calcium deposits in arterial walls, and an intra-cerebral lipoma in the corpus callosum in their patient. Plumbagin concentration Shortcomings of the study are that the diagnostic criteria for MERRF were not accomplished, that the patient should be rather diagnosed as a mitochondrial, multiorgan disorder syndrome (MIMODS), that no pedigree and heteroplasmy rates in first degree relative were provided, that hormone levels were not provided despite obvious endocrinological involvement, and that no serum or cerebrospinal fluid (CSF) lactate levels were reported.Historical Museums of Anatomical Pathology are a relevant teaching tool for medical undergraduate students and postgraduate residents. The visualization of real specimens allow a deeper comprehension of diseases, namely of rare conditions as in Teratology. This article emphasizes the need to preserve and use Universities Museums, by presenting a XIXth Thoraco-Abdominopagus Fetus.Genital and pelvic endometriosis is a frequently encountered lesion and its importance rely on associated symptoms and its propensity for malignant transformation. In the present paper we comment on the importance of correctly diagnose the malignant transformation of an endometriotic lesion into a cystic low-grade endometrial stromal sarcoma, which is a very rare event. Moreover, we discuss the ability of a low-grade endometrial stromal sarcoma to locally recurr and the differential diagnosis with stromal endometriosis, a lesion that is very rare, almost always microscopic and solid.Multiple sclerosis (MS) is an autoimmune and degenerative disorder of the central nervous system (CNS) that causes a progressive loss of motor and cognitive performances. Moreover, since the earlier phases, axonal loss as well as neuronal degeneration and a failure of oligodendrocytes to promote myelin repair have been demonstrated. In previous studies, it has been shown that the treatment of rat neuronal primary cultures with serum from MS patients can be toxic for neurons. Here we report a pilot investigation showing that CSF from patients contains extracellular vesicles (EVs) able to induce cell death in rat cultured astrocytes. Although these data are still preliminary, they suggest at least two notable considerations i) EVs can be instrumental to pathology, and their concentration in CSF might be proportional to MS severity; ii) astrocytes can be part of the degenerative process. As a consequence, we propose that cultured astrocytes can be used as a model to study the toxicity of EVs from patients affected by MS at different stages.