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The Russian airline market for the first time since the sharp decline in passenger traffic in 2020 showed growth rates of revenue per passenger-kilometre in 2021. This indicates a step towards recovery after the biggest crisis the industry has seen in all of history. The purpose of the study is to assess the financial stability of the Russian air carriers for the last three years: 2019 (pre-COVID-19), 2020 (COVID-19) and 2021 (post-COVID-19), with the help of applying bankruptcy likelihood prediction models. The analysis was conducted for 4 airlines, each of them having a different business model that they follow (national flag carrier, low-cost carrier, ultra-low-cost carrier and regional carrier). The market positions of each airline were identified, highlighting the rapid growth of low-cost carriers, even during the COVID-19 crisis. The same cannot be said for full-service airlines, which have fallen the most in both profit and traffic. Calculations of bankruptcy models showed that low-cost airlines were more financially stable during the COVID-19 pandemic, while full-service air carriers experienced uncertainty during 2020 and only gradually recovered in 2021. These results coincide with other research regarding which business model is less vulnerable during crises, however this is very dependent on the region in which airlines operate in: both low-cost carriers and full-services airlines, according to other authors, show high financial sustainability. Such contradiction in the current research highlights the relevance of further analysis in this area to provide answers that are more concrete.

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in JAG1 or less frequently, mutations in NOTCH2. The disease has been difficult to diagnose and treat due to variable expression. The generation of this iPSC line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent need for effective therapeutic options. SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic that has resulted in significant morbidity and mortality worldwide. The virus is known to enter host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, and emerging evidence suggests that heparan sulfate proteoglycans (HSPGs) play a crucial role in facilitating this process. HSPGs are abundant cell surface proteoglycan present in many tissues, including the lung, and have been shown to interact directly with the spike protein of SARS-CoV-2. This review aims to summarize the current understanding of the role of HSPGs in SARS-CoV-2 infection and the potential of developing new therapies targeting HSPGs.

Abstract SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering, forming synapse-like cell-cell contacts that facilitate fusion pore formation between ACE2-expresing and spike-transfected human cells. Chemical or genetic inhibition of HS mitigates ACE2 clustering, and thus, syncytium formation, whereas in a cell-free system comprising purified HS and lipid-anchored ACE2, HS stimulates ACE2 clustering directly in the presence of spike. Furthermore, HS-stimulated syncytium formation and receptor clustering require a conserved ACE2 linker distal from the spike-binding site. Importantly, the cell fusion-boosting function of HS can be targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice. Thus, HS, as a host factor exploited by SARS-CoV-2 to facilitate receptor clustering and a stimulator of infection-associated syncytium formation, may be a promising therapeutic target for severe COVID.

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in either the JAG1 gene (ALGS type 1) or the NOTCH2 gene (ALGS type 2). The disease has been difficult to diagnose and treat due to its muti-system clinical presentation, variable expressivity, and prenatal onset for some of the features. The generation of this iPSC line (TRNDi032-A) carrying a heterozygous mutation, p.Cys682Leufs*7 (c.2044dup), in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.

Expanded human lymphoblast cells from three different aged healthy individuals, 8-year-old male, 0-year-old newborn (NB) male, and 26-year-old female, were used to generate induced pluripotent stem cell (iPSC) lines TRNDi033-A, TRNDi034-A and TRNDi035-A, respectively, by exogenous expression of five reprogramming factors, human OCT4, SOX2, KLF4, L-MYC and LIN28. The authenticity of established iPSC lines was confirmed by the expressions of stem cell markers, karyotype analysis, embryoid body formation, and scorecard analysis. These iPSC lines could serve as healthy donor controls that are age and sex matched for the studies involving patient-specific iPSCs.

NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations–one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency.

The ability to model human neurological tissues in vitro has been a major hurdle to effective drug development for neurological disorders. iPSC-derived brain organoids have emerged as a compelling solution to this problem as they have the potential to relevantly model the protein expression pattern and physiology of specific brain regions. Although many protocols now exist for the production of brain organoids, few attempts have been made to do an in-depth kinetic evaluation of expression of mature regiospecific markers of brain organoids. To address this, we differentiated midbrain-specific brain organoids from iPSC-lines derived from three apparently healthy individuals using a matrix-free, bioreactor method. We monitored the expression of midbrain-specific neuronal markers from 7 to 90-days using immunofluorescence and immunohistology. The organoids were further characterized using electron microscopy and RNA-seq. In addition to serving as a potential benchmark for the future evaluation of other differentiation protocols, the markers observed in this study can be useful as control parameters to identify and evaluate the disease phenotypes in midbrain organoid derived from patient iPSC-lines with genetic neurological disorders.

Hydroelectricity remains the dominate RES (Renewable Energy Source) and the most developed, reaching growth rate peaks in some countries in the 20th century. However, the share of it has fallen over the last few years, as other renewable sources have received rapid development. Despite this, growth for hydroelectricity has remained stable, with China, India, Japan, Russia, Turkey, France, Norway, Canada, USA and Brazil as market leaders. This article analyzes the key trends of development of the hydroelectricity market as a whole, as well as the financial stability of its organizations using bankruptcy likelihood prediction models. The Brazilian and Russian companies were chosen to assess as both countries are classified as developing markets. The bankruptcy prediction models indicate that overall, the financial stability of hydroelectricity giants of Brazil and Russia is at a high level, though profitability ratios are very low. During the COVID-19 pandemic, several financial support measures were implemented by governments, along with the already existing instruments for stimulating renewable energy growth. Authors’ forecasts show that current trends on the market indicate that net addition capacity growth in the next few years will not be enough to meet Net Zero goals for the renewables market.

The metrological analysis of non-destructive methods determined the diffusion coefficient in block products formed from porous materials is considered. The methods are based on both various types of pulsed effects on the products flat surface and their reaction monitoring in terms of electromotive force changes of an electrochemical converter. The developed technique obviates long transducer calibration stage for each new porous material and diffusing polar solvent, increasing the analysis efficiency. The analyzed methods application areas are substantiated in the context of ensuring acceptable accuracy including in the presence of pronounced anisotropy of properties.

NGLY1 deficiency is a rare recessive genetic disease caused by mutations in the NGLY1 gene which codes for N-glycanase 1 (NGLY1). Here, we report the generation of two gene corrected iPSC lines using a patient-derived iPSC line (NCATS-CL6103) that carried a homozygous p.R401X mutation in the NGLY1 gene. These lines contain either one (NCATS-CL6104) or two (NCATS-CL6105) CRISPR/Cas9 corrected alleles of NGLY1. This pair of NGLY1 mutation corrected iPSC lines can be used as a control for the NCATS-CL6103 which serves as a cell-based NGLY1 disease model for the study of the disease pathophysiology and evaluation of therapeutics under development.