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Aim Inositol polyphosphate kinases are involved in regulation of many cellular processes in eukaryotic cells. In this study, we investigated the functions of the inositol polyphosphate kinase Vip1 in autophagy and pathogenicity of Candida albicans. Results Loss of Vip1 caused significantly increased sensitivity to nitrogen source starvation, abnormal localization and degradation of autophagy protein, higher vacuolar pH and higher (rather than lower) intracellular ATP levels compared with control strains. Besides, the mutant showed attenuated hyphal development and virulence during systemic infection to mice. Conclusion The results reveal that Vip1 is important to autophagy of C. albicans. The maintenance of vacuolar acidic pH contributed to the role of Vip1 in autophagy. Vip1 is also required for pathogenicity of C. albicans.As the global COVID-19 pandemic spreads worldwide, new challenges arise in the clinical landscape. The need for reliable diagnostic methods, treatments and vaccines for COVID-19 is the major worldwide urgency. While these goals are especially important, the growing risk of co-infections is a major threat not only to the health systems but also to patients’ lives. Although there is still not enough published statistical data, co-infections in COVID-19 patients found that a significant number of patients hospitalized with COVID-19 developed secondary systemic mycoses that led to serious complications and even death. This review will discuss some of these important findings with the major aim to warn the population about the high risk of concomitant systemic mycoses in individuals weakened by COVID-19.

The type 1 interferon pathway is known to play a role in the immunopathology of systemic lupus erythematosus (SLE). As a result, biologic agents targeting this pathway have been developed and are currently being investigated in clinical trials.

We review the biologic agents which have been developed to antagonize type I interferons in SLE. We focus on anifrolumab, a type I interferon receptor antagonist, and consider the complexities of defining efficacy in SLE clinical trials.

Anifrolumab shows promise as an addition to the SLE therapeutic armamentarium. Despite discordant results between its two phase III studies, there is a convincing suggestion of benefit in both trials to encourage the view that this approach might be effective. Data acquired thus far look particularly useful for cutaneous disease. We await data on its effect on renal, pulmonary, cardiac, and central nervous system involvement, on patient reported outcomes, and its safety and efficacy with long-term use.

Anifrolumab shows promise as an addition to the SLE therapeutic armamentarium. Despite discordant results between its two phase III studies, there is a convincing suggestion of benefit in both trials to encourage the view that this approach might be effective. Data acquired thus far look particularly useful for cutaneous disease. We await data on its effect on renal, pulmonary, cardiac, and central nervous system involvement, on patient reported outcomes, and its safety and efficacy with long-term use.The rearrangement distance is a well-known problem in the field of comparative genomics. Given two genomes, the rearrangement distance is the minimum number of rearrangements in a set of allowed rearrangements (rearrangement model), which transforms one genome into the other. In rearrangement distance problems, a genome is modeled as a string, where each element represents a conserved region within the two genomes. When the orientation of the genes is known, it is represented by (plus or minus) signs assigned to the elements of the string. Two of the most studied rearrangements are reversals, which invert a segment of the genome, and transpositions, which exchange the relative positions of two adjacent segments of the genome. The first works in genome rearrangements considered that the genomes being compared had the same genetic material and that rearrangement events were restricted to reversals, transpositions, or both. El-Mabrouk extended the reversal model on signed strings to include the operations of insertion and deletion of segments in the genome, which allowed the comparison of genomes with different genetic material. Other studies also addressed this problem and, recently, this problem was proved to be solvable in polynomial time by Willing et al. For unsigned strings, we still observe a lack of results. That said, in this study we prove that computing the rearrangement distance for the following models is NP-Hard reversals and indels on unsigned strings; transpositions and indels on unsigned strings; and reversals, transpositions, and indels on signed and unsigned strings. Along with the NP-hardness proofs, we present a 2-approximation algorithm for reversals on unsigned strings and 3-approximation algorithms for the other models.Background Fibroblast growth factor 23 (FGF23) has become increasingly important in chronic kidney diseases (CKDs), cardiovascular calcification, and metabolic bone diseases. Fresh or stored blood samples are widely used for the FGF23 assay. Clarifying the factors influencing the FGF23 assay can help to quantify FGF23 more accurately. This study explored the effects of low-temperature storage time and repeated freeze-thaw cycles on the measurement of serum intact FGF23 (iFGF23). Materials and Methods We selected 60 serum samples from patients with CKD stages 3-5 and hemodialysis patients. An enzyme-linked immunosorbent assay was used to measure the changes in serum iFGF23 levels after 6 years of storage at -80°C. In total, 18 fresh serum samples were frozen and thawed for 0, 1, 3, and 5 cycles to explore the effects of repeated freeze-thaw cycles on serum iFGF23 levels. Results Median serum iFGF23 concentrations were 252.17 (interquartile range [IQR] 113.82-592.38) pg/mL and 203.85 (IQR 64.76-545.39) pg/mL before and after 6 years. There were no significant differences between them. Selleck Belnacasan However, we found a downward trend of 48% in the samples close to the normal level of iFGF23 ( less then 150.34 pg/mL) after 6 years of storage (p = 0.160). In addition, the iFGF23 levels of samples frozen and thawed for 0, 1, 3, and 5 cycles were 278.41 ± 39.51 (mean ± standard deviation) pg/mL, 262.84 ± 38.42 pg/mL, 252.97 ± 34.65 pg/mL and 250.49 ± 37.12 pg/mL, respectively. A slight downward trend in iFGF23 levels was observed with increasing freeze-thaw times; however, no significant differences were found among different freeze-thaw cycles. Conclusion Serum iFGF23 levels remained stable after storage at -80°C for 6 years. In addition, five freeze-thaw cycles had no significant effects on serum iFGF23 levels.