Bechjonasson0021
Human herpesvirus 6A (HHV-6A) is a member of the genus Roseolovirus and the subfamily Betaherpesvirinae. It is similar to and human cytomegalovirus (HCMV). HHV-6A encodes a 41 kDa nuclear phosphoprotein, U27, which acts as a processivity factor in the replication of the viral DNA. HHV-6A U27 has 43% amino acid sequence homology with HCMV UL44, which is important for DNA replication. A previous study on HHV-6A U27 revealed that it greatly increases the in vitro DNA synthesis activity of HHV-6A DNA polymerase. However, the role of U27 during the HHV-6A virus replication process remains unclear. In this study, we constructed a U27-deficient HHV-6A mutant (HHV-6ABACU27mut) with a frameshift insertion at the U27 gene using an HHV-6A bacterial artificial chromosome (BAC) system. Viral reconstitution from the mutant BAC DNA was not detected, in contrast to the wild type and the revertant from the U27 mutant. This suggests that U27 plays a critical role in the life cycle of HHV-6A.Cardiac injuries are recorded after multiple trauma and are associated with a poor patient outcome. Reaming prior to locked intramedullary nailing is a frequently used technique to stabilize femoral diaphysis fractures. However, in polytraumatized patients, complications such as fat emboli and acute respiratory distress syndrome have been associated with reaming. The reaming irrigator aspirator (RIA) system provides concomitant irrigation and suction of the intramedullary contents, and should, therefore, reduce reaming-associated complications. The aim of the study was to investigate cardiac function after multiple trauma with regard to two different RIA devices (RIAI vs RIAII). 15 male pigs were included in the study. Pigs received either sham treatment or multiple trauma (chest trauma, femur fracture, liver laceration, and hemorrhagic shock), followed by intramedullary nailing after reaming with either the RIAI or RIAII system (RIAII reduced diameter of the reamer, improved control of irrigation and suction). Cardiac function was assessed by transesophageal echocardiography and systemic inflammation as well as local cardiac damage examined. Pigs of both treatment groups showed impaired cardiac function, valvular insufficiency, and cardiac damage. Systemic inflammation and local cardiac alterations were observed which might contribute to early myocardial damage in vivo. Multiple trauma including long-bone fracture and subsequent intramedullary reaming induces cardiac dysfunction and valvular insufficiency, which might be linked to both mechanical cardiac injury and increased systemic inflammation. 6 hours after trauma there are less differences between RIAI and RIAII treatment with regard to post-traumatic cardiac consequences in multiple injured pigs, indicating no beneficial effect of RIAII over RIAI.Osteoarthritis (OA) is a disease of the entire joint, often triggered by cartilage injury, mediated by a cascade of inflammatory pathways involving a complex interplay among metabolic, genetic, and enzymatic factors that alter the biochemical composition, microstructure, and biomechanical performance. Clinically, OA is characterized by degradation of the articular cartilage, thickening of the subchondral bone, inflammation of the synovium, and degeneration of ligaments that in aggregate reduce joint function and diminish quality of life. OA is the most prevalent joint disease, affecting 140 million people worldwide; these numbers are only expected to increase, concomitant with societal and financial burden of care. We present a two-part review encompassing the applications of nanotechnology to the diagnosis and treatment of OA. Herein, part 1 focuses on OA treatment options and advancements in nanotechnology for the diagnosis of OA and imaging of articular cartilage, while part 2 (10.1002/jor.24842) summarizes recent advances in drug delivery, tissue scaffolds, and gene therapy for the treatment of OA. Specifically, part 1 begins with a concise review of the clinical landscape of OA, along with current diagnosis and treatments. We next review nanoparticle contrast agents for minimally invasive detection, diagnosis, and monitoring of OA via magnetic resonace imaging, computed tomography, and photoacoustic imaging techniques as well as for probes for cell tracking. We conclude by identifying opportunities for nanomedicine advances, and future prospects for imaging and diagnostics.Thermally activated delayed fluorescence (TADF) is generally observed in solid-state organic molecules or metal-organic complexes. However, TADF in all-inorganic colloidal nanocrystals (NCs) is rare. Herein, we report the first colloidal synthesis of an air-stable all-inorganic lead-free Cs2 ZrCl6 perovskite NCs. The Cs2 ZrCl6 NCs exhibit long-lived triplet excited state (138.2 μs), and feature high photoluminescence (PL) quantum efficiency (QY=60.37 %) due to TADF mechanism. The emission color can be easily tuned from blue to green by synthesizing the mixed-halide Cs2 ZrBrx Cl6-x (0≤x≤1.5) NCs. Femtosecond transient absorption and temperature dependent PL measurements are performed to clarify the emission mechanism. In addition, Bi3+ ions are successfully doped into Cs2 ZrCl6 NCs, which further extends the PL properties. This work not only develops a new lead-free halide perovskite NCs for potential optoelectronic applications, but also offers unique strategies for developing new inorganic phosphors.Viral gastroenteritis is a major source of morbidity and mortality, predominantly caused by so-called NOROAD viruses (norovirus, rotavirus, and adenovirus). In approximately onethird of all cases, however, the exact etiology is unknown. The in 2007 discovered human cardiovirus Saffold virus (SAFV) may prove to be a plausible candidate to explain this diagnostic gap. This virus, a member of the Picornaviridae family which is closely related to the murine viruses Theiler's murine encephalomyelitis virus and Theravirus, is a widespread pathogen and causes infection early in life. Screening of 238 fecal or vomitus samples obtained from NOROAD-negative, elderly patients with acute gastroenteritis at the University Hospital of Linköping showed that SAFV is present in low abundance (4.6%). Phylogenetic analysis of the VP1 gene revealed a Swedish isolate belonging to the highly common and in Europe widespread SAFV-3 genotype. This genotype is also related to previously reported Asian strains. This study describes the first molecular typing of a Swedish SAFV isolate and is the first report to document the circulation of SAFV among elderly people. The pathogenicity of SAFV is, as of yet, still under debate; further studies are necessary to determine its role in the development of disease.Biocatalytic cascade reactions have become increasingly important and useful for chemical synthesis. However, biocatalysts are often incompatible with organic solvents, which prohibits many cascade reactions involving nonpolar substrates. In this study, we used cell-free protein synthesis (CFPS) to express enzymes in an aqueous-organic biphasic system for the construction of an artificial enzymatic pathway. CFPS-expressed enzymes without purification performed efficiently to convert styrene (below 20 mM) to (S)-1-phenyl-1,2-ethanediol (two steps in one pot) with 100% conversion. In addition, our CFPS system showed great tolerance to different organic solvents, and, importantly, the entire biocatalytic system can be consistently scaled up without a reduction of the substrate conversion rate. We, therefore, anticipate that our cell-free approach will make a possible cost-effective, high-yielding synthesis of valuable chemicals.We report a first of its kind functional cell surface display of nucleic acid polymerase and its directed evolution to efficiently incorporate 2'-O-methyl nucleotide triphosphates (2'-OMe-NTPs). Resveratrol In the development of polymerase cell surface display, two autotransporter proteins (Escherichia coli adhesin involved in diffuse adherence and Pseudomonas aeruginosa esterase A [EstA]) were employed to transport and anchor the 68-kDa Klenow fragment (KF) of E. coli DNA polymerase I on the surface of E. coli. The localization and function of the displayed KF were verified by analysis of cell outer membrane fractions, immunostaining, and fluorometric detection of synthesized DNA products. The EstA cell surface display system was applied to evolve KF for the incorporation of 2'-OMe-NTPs and a KF variant with a 50.7-fold increased ability to successively incorporate 2'-OMe-NTPs was discovered. Expanding the scope of cell-surface displayable proteins to the realm of polymerases provides a novel screening tool for tailoring polymerases to diverse application demands in a polymerase chain reaction and sequencing-based biotechnological and medical applications. Especially, cell surface display enables novel polymerase screening strategies in which the heat-lysis step is bypassed and thus allows the screening of mesophilic polymerases with broad application potentials ranging from diagnostics and DNA sequencing to replication of synthetic genetic polymers.
We evaluated the clinical applications of the reconstruction of postoperative defects of the oral cavity using contralateral submental artery flaps.
A retrospective study of 18 patients with postoperative intraoral cancer defects reconstructed with contralateral submental artery perforator flaps between October 2018 and October 2019 in our department was conducted. The defect area, flap size, and complications were evaluated.
All patients were diagnosed based on pathological examinations 2 with adenoid cystic carcinoma and 16 with squamous cell carcinoma. The submental artery perforator flap used for simultaneous repair was 8 to 15 cm in length and 4 to 6.5 cm in width. The survival rate of flap reconstruction was 100% with no donor site complications.
Contralateral submental artery flap reconstruction is a suitable alternative for moderate to large intraoral defects, postoperative mouth floor defects, and oral cavity composite defects of oral malignant tumors without contralateral lymph node metastases.
Contralateral submental artery flap reconstruction is a suitable alternative for moderate to large intraoral defects, postoperative mouth floor defects, and oral cavity composite defects of oral malignant tumors without contralateral lymph node metastases.Influenza A virus (IAV) causes great morbidity and mortality worldwide every year. However, there are only a limited number of drugs clinically available against IAV infection. Further, emergence of drug-resistant strains can render those drugs ineffective. Thus there is an unmet medical need to develop new anti-influenza agents. In this study, we show that punicalagin from plants possesses strong anti-influenza activity with a low micromolar IC50 value in tissue culture. Using a battery of bioassays such as single-cycle replication assay, neuraminidase (NA) inhibition assay, and virus yield reduction assay, we demonstrate that the primary mechanism of action (MOA) of punicalagin is the NA-mediated viral release. Moreover, punicalagin can inhibit replication of different strains of influenza A and B viruses, including oseltamivir-resistant virus (NA/H274Y), indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV. Further, although punicalagin targets NA like oseltamivir, it has a different MOA.