Malignant fibrous histiocytoma of the bone (MFH-B) is an extremely rare and aggressive malignancy. The clinicopathological characteristics and prognosis of patients with MFH-B have not been defined. We conducted a retrospective study using the data of all MFH-B patients from the Surveillance, Epidemiology and End Results (SEER) database between 1975 and 2016. Initially, the clinicopathological characteristics were described. The difference in prognosis between patients with MFH-B and those with osteosarcoma was compared using propensity score matching analysis. Then, the features affecting the prognosis of patients with MFH-B were further determined using Cox regression analysis. A total of 318 patients with MFH-B were identified. The median overall survival (mOS) of all 318 patients with MFH-B was 29.0 months. The 1-, 3-, 5-, and 10- year survival rates were 67.4%, 53.6%, 38.7%, and 28.7%, respectively. The multivariate Cox regression analysis showed that older age, distant metastases, and flat bone lesion were independent factors for worse prognosis, whereas surgery was an independent factor for favorable survival, and this intervention could decrease risk of death by 61% (HR = 0.39, 95% CI 0.28-0.54). Apart from this, the prognosis of patients with MFH-B was significantly worse than that of patients with osteosarcoma in both unmatched and matched cohorts. In conclusion, MFH-B is a rare malignant bone cancer, with relatively worse prognosis than osteosarcoma. Older age, distant metastases, flat bone lesion, and surgery were independently associated with prognosis. In order to understand this disease more thoroughly and accurately, more cases with adequate information are required in the future.Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera.Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the Togaviridae family, is part of a group of emergent diseases, including arbovirus, constituting an increasing public health problem in tropical areas worldwide. CHIKV causes a severe and debilitating disease with high morbidity. The first Colombian autochthonous case was reported in the Colombian Caribbean region in September 2014. Within the next two to three months, the CHIKV outbreak reached its peak. Although the CHIKV pattern of clinical symptomatology has been documented in different epidemiological studies, understanding of the relationship between clinical symptomatology and variation in phenotypic response to CHIKV infection in humans remains limited. We performed a cross sectional study following 1160 individuals clinically diagnosed with CHIKV at the peak of the Chikungunya outbreak in the Colombian Caribbean region. We examined the relationship between symptomatology and diverse phenotypic responses. Latent Class Cluster Analysis (LCCA) ed to validate these results and determine whether the distinct LCCA profiles are a result of the immune response or a mixture of genetic, lifestyle and environmental factors. Our findings could contribute to the development of machine learning approaches to characterizing CHIKV infection in other populations. Preliminary results have shown prediction models achieving up to 92% accuracy overall, with substantial sensitivity, specificity and accuracy values per LCCA-derived cluster.Acute myeloid leukemia (AML) is a genetically heterogeneous group of oncological diseases of the hematopoietic system, which are extremely difficult to treat. The development of new targeted drugs (Hylteritinib, Venetoclax) significantly improved the survival of patients, but resistance, as well as cytotoxic anti-leukemia drugs, often occurs. The search for new molecular targets for the development of effective approaches for the treatment of AML is very urgent. In blast cells of patients with AML, mutations, chromosomal rearrangements, and increased expression of a number of non-mutant genes, including transcription factor genes, are detected. The transcription factor Sp 1 binds to GC-rich regions of regulatory regions of various genes and thus controls their expression. Sp1 targets include genes responsible for proliferation, cell cycle regulation, and differentiation. In many malignant diseases, a high level of Sp1 gene expression is associated with an unfavorable prognosis, therefore, Sp1 is considered asare most sensitive to inhibition of Sp1 activity in order to assess the possibility of suppressing its activity in vivo.Post-translational hydroxylation occurs in three mammalian ribosomal proteins, uS12, uL2, and uL15, which are located in the small (S) and large (L) subunits of the ribosome near the most important decoding and peptidyltransferase functional centers. We have used cell cultures, which produce protein uL15 labeled with the 3xFLAG epitope at the C-terminus (uL15^(3xFLAG)) or mutant forms of uL15^(3xFLAG) that contain His39Ala, His39Thr, or His40Ala substitutions, to examine the role of hydroxylated His39 of uL15 in maintaining the translational activity of ribosomes. It has been found that exogenous uL15^(3xFLAG) is able to functionally replace endogenous uL15 in HEK293 cells transfected with an appropriate DNA construct. However, the translational activity of ribosomes decreases by about 35% in cells that produce the above mutant forms of uL15^(3xFLAG) compared with that in cells that produce nonmutated uL15^(3xFLAG). Analysis of the structural model of the human ribosome has allowed us to assume that the hydroxyl group in His39 is involved in the local stabilization of the ribosome structure through the formation of a hydrogen bond between this group and the nitrogen atom of the His40 imidazole ring. Given that His39 is located near the E site of the ribosome, we believe that this stabilization of the ribosome structure ensures the maintenance of its translational activity.Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.Plasmid-mediated gene therapy, being a safe and relatively inexpensive therapeutic strategy, is plagued by a fast silencing of transgene expression. The silencing severely reduces the long-term efficiency of plasmid vectors. We have earlier constructed a low-CpG pMBR2 plasmid vector supporting prolonged expression of transgenes in mesenchymal stem cells in vitro. Long-term expression from the pMBR2 vector was studied for the wild-type mouse secreted alkaline phosphatase gene (mSEAPTwt) and its version devoid of CpGs (mSEAP0) after vector electroporation into mouse hindlimb muscles and hydrodynamic delivery to the liver. The mSEAP levels in the blood were measured over one year. With the pMBR2-mSEAP0 construct, the mSEAP levels in leg muscles increased more than 2.5-fold in the first two months and remained higher than the initial level until the end of the experiment. Far lower expression levels were observed with the control pCDNA3.1-mSEAP0 construct. Expression from pMBR2-mSEAPwt decreased to about 40% after 6 months and remained at similar levels thereafter. In the mouse liver, expression from pMBR2-mSEAP0 was approximately halved within the first 18 weeks and then decrease slowly to the final 17% level. Expression from pMBR2-mSEAPwt initially dropped to 18% and remained at approximately 10% thereafter. In contrast, expression from pCDNA3.1-mSEAP0 sharply dropped to 5% after 2 weeks and remained at nearly zero levels throughout the rest of the experiment. Thus, both vector and transgene should have significantly reduced CpG contents to ensure prolonged plasmid-mediated expression in the liver, while minimizing the vector CpG content is sufficient for expression in skeletal muscles. The results suggested additionally that the localization of S/MAR elements within the transcription unit, in contrast to their outside location, results in significant reduction of the level of secreted, but not cytoplasmic, proteins.The abundance of noncanonical mechanisms of eukaryotic initiation of translation indicates their involvement in the regulation of protein synthesis during key events in a cell life. One of the well-known examples of a noncanonical cap-independent process is the initiation of translation of mRNA with the 5′-untranslated (leader) region of the messenger encoding for the photoprotein obelin (the obelin leader). In the present work, mRNA with the obelin leader was modified by adding 45 deoxycytidyl nucleotides and a fluorescent label to its 5’end. Formation of the 48S ribosomal initiation complexes at the start codon of the modified mRNA was studied using primer extension inhibition (toeprinting). In contrast to mRNA with the intact obelin leader, translation initiation of which strictly requires the eIF4F factor, initiation on the modified mRNA can take place in the absence of this factor, although with less efficiency. The finding thus indicates the unknown function of the eIF4F factor in the first step(s) of mRNA recognition by ribosomal subunits.