Progressive Form Research Articles

Methodical system of training future english language teachers based on a complex of approaches

Introduction. The article describes a methodical system for developing professional competencies of future English language teachers based on communicative, cognitive and synergetic approaches. The relevance of the study is due to the need to ensure effective professional training of future teachers in the context of the increasing complexity of the educational environment and the diversity of student needs. The purpose of the study is to design a methodical system based on a complex of approaches that allows creating more adaptive and flexible conditions for the training and professional development of future English language teachers, taking into account modern requirements and challenges in the field of education. Materials and Methods. During the study, a theoretical analysis of scientific literature and legal documents on the issue under study was carried out, as well as a comparative analysis of existing concepts of methodical systems and models for the formation of professional competencies of future teachers. The methods of analysis, synthesis, comparison, generalization and modelling are used in the study. Results. As a result of theoretical and comparative analysis of scientific research, generalization of our own practical experience, a methodical system for developing professional competencies of future English language teachers based on a complex of approaches has been developed, its key components, which ensure the comprehensive and systematic nature of the educational process, have been described, as well as the mechanism of their interaction. All components of the system are presented in target, content, conceptual and methodical, effective blocks. Discussions and Conclusions. The development of a methodology for the formation of professional competencies of future English language teachers based on communicative, cognitive and synergetic approaches in the process of studying special disciplines with a focus on the integration of disciplinarydevelopment and the progressive formation of competencies is a prospect for further research.

A novel high-Mn duplex twinning-induced plasticity lightweight steel with high yield strength and large ductility

In this study, we report a novel high-Mn Fe–21Mn–6Al–4Si–1C (wt.%) duplex lightweight steel with concurrent chemical ordering and twinning-induced plasticity effects. This steel is capable of achieving an exceptional combination of strength and ductility following either cold-rolling and annealing at 1000 °C or subsequent short-term aging at 550 °C. In its as-annealed state, this steel primarily consists of γ-austenite and α-ferrite, with α-ferrite appearing as dispersed particles within fully recrystallized γ grains. Furthermore, L′12- and D03-type ordered nanodomains exist within these two phases, respectively. The aging treatment negligibly affects the size and volume fraction of both the γ-austenite and α-ferrite, yet it enhances the degree of ordering as well as the size and volume fraction of their ordered nanodomains, leading to a rise in yield strength from ∼800 to ∼1062 MPa and a decline in total elongation from ∼60.4% to ∼44.4%. The high yield strength of this steel originates from multiple strengthening mechanisms involving dislocation interactions with solute atoms, ordered nanodomains, γ grain boundaries and γ/α phase boundaries. This steel plastically deforms via planar slip during the initial stages. The rather small γ grain size, coupled with the presence of hard α-ferrite particles, fosters the dynamic slip band refinement (DSBR) effect, thereby enhancing the flow stress sufficiently to trigger deformation twinning in the steel during the later stages. The DSBR effect, combined with the progressive formation of deformation twins, stacking faults and Lomer-Cottrell locks, imparts pronounced strain hardenability to this steel, leading to its outstanding ductility.

Profile of patients with Juvenile Dermatomyositis and Anti-MDA5 autoantibodies.

Anti-MDA5 autoantibody-positive dermatomyositis (MDA5-DM) is associated with clinically amyopathic forms and rapidly progressive interstitial lung disease (ILD); however, data in children are limited. In this study, we described our cohort of anti-MDA5-positive juvenile DM (MDA5-JDM) from a tertiary care center in North India. We performed a retrospective analysis of children with MDA5-JDM who were diagnosed and followed up at our center and compared them with our anti-MDA5-negative cohort. We also compared the published literature on MDA5-DM with the juvenile cohort. Of 66 children with JDM who underwent testing for MSA, 10(15.5%) had anti-MDA5 positivity. The mean age at onset of clinical manifestations was 8.4 years; male: female ratio was 7:3. Five of nine patients who underwent screening HRCT chest had ILD; one amongst them had a fatal rapidly progressive disease. Children with MDA5-JDM had significantly more arthralgia/arthritis (p = 0.006) and ILD (p = 0.0005) compared to anti-MDA5 negative JDM in our cohort. While MDA5-DM had high rates of Raynaud's phenomenon (p = 0.04) and pulmonary involvement (p = 0.001), juvenile patients had a higher prevalence of constitutional symptoms (p = 0.01), skin manifestations (p = 0.003), arthritis (p = 0.001), and muscle weakness (p = 0.001). Arthritis and ILD are commonly seen with MDA5-JDM; however, the frequency of ILD and clinically amyopathic forms are less common compared to adult counterparts. The frequency of anti-MDA5 antibodies in a North Indian cohort of JDM is much lower (15.5%) compared to adult studies in dermatomyositis from Southeast Asia (~25%). Incidence of interstitial lung disease (ILD) and arthritis is high in anti-MDA5 autoantibody-positive JDM. Rates of a rapidly progressive form of ILD and clinically amyopathic dermatomyositis are much lower in children compared to adults with anti-MDA5-associated dermatomyositis.

Debris‐flow fan channel avulsions: An important secondary erosional process along the Ichino‐sawa torrent, Japan

AbstractSediment transported from debris‐flow initiation zones is typically stored in a topographic feature called a debris‐flow fan, the formation process of which governs secondary sediment transport further downstream. Although sediment transport from debris‐flow fans can impact sediment regimes and change landforms, the determinants of progressive fan formation are not well constrained. To identify such determinants, this study monitored debris flows and performed topographic surveys of debris‐flow fans in the Ichino‐sawa torrent (Japan) during 2016–2017. In this period, eight debris flows occurred, two of which eroded the existing fan and formed a new channel with a short recurrence interval (~40 days). Consequently, these two cases induced substantial sediment transport further downstream from the fan. The examined rainfall indices did not provide a threshold for diagnosing the occurrence of such sediment transport. Debris flows with a large flow depth and a long duration led to changes in the runout direction and subsequently formed new channels. Before these processes, the existing channel was backfilled and plugged by previous debris flows, forming a steep fan surface around the fan apex. The results suggest that increasing the magnitude and the duration of debris flows potentially triggers sediment transport from fans coupled with channel plugging. The annual sediment transport from the fan exceeded almost all sediment yields of the world rivers and was found comparable with that linked with volcanic eruptions and their aftermath. Thus, the fan‐formation process can induce substantial sediment transport, independent of volcanic perturbations and extreme climatic events, and is dependent on the sediment supply from repeated occurrence of debris flows in the initiation zones.

Identification of novel likely pathogenic variant in CDH23 causing non-syndromic hearing loss, and a novel variant in OTOGL in an extended Iranian family

BackgroundSensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the GJB2 and GJB6 genes are among the most common causes of SNHL worldwide. Mutations in Cadherin 23 (CDH23) can cause Usher syndrome and/or non-syndromic hearing loss (NSHL).Material and methodsIn this study, the Whole Exome Sequencing (WES) was used to detect the cause of hearing loss in a large consanguineous Iranian family with two patients. All family members underwent a thorough Genotype–phenotype correlation assessment and co-segregation analysis to understand the inheritance pattern within the family. The candidate variants were further confirmed by Sanger sequencing. In addition, in silico analysis was performed to predict the functional impact of the variants; the interpretation of the variants was performed in accordance with the American College of Medical Genetics (ACMG) guidelines.ResultsWES results identified two novel variants, a homozygous missense variant in CDH23 (c.2961T > G) and a heterozygous splice site variant in OTOGL that was compatible with the autosomal recessive pattern of inheritance. Bioinformatics studies confirmed the pathogenic effects of novel variants. The c.2961T > G variant was classified as likely pathogenic.ConclusionsThe novel identified variant in the CDH23 was the cause of congenital profound progressive form of HL. Samples were not available from the second family to distinguish which variant is responsible for the molecular pathology of the disease. Further studies and functional examinations are suggested for investigating the role of OTOGL: c. 1863-1G > T in deafness.

ON THE IMPLEMENTATION BY THE PEOPLE’S COMMISSARIAT OF LIGHT INDUSTRY OF THE USSR OF THE RESOLUTIONS OF THE STATE DEFENCE COMMITTEE IN THE 2ND HALF OF 1941

This article examines the process of implementation by the People’s Commissariat of Light Industry of the USSR of the resolutions of the State Defence Committee on the production of clothing and equipment for the acting army. At the same time, the most difficult period for the Soviet state is covered – the 2nd half of 1941. The resolutions are examined in chronological order, as they were adopted, which allows us comprehending the progressive formation of the experience of state management of the economy of various industries and, above all, light industry. Moreover, they allow us getting an idea of the needs of the Red Army during that period, state measures aimed not only at replenishing military equipment lost in the first months of the battles, but also increasing production of uniforms, primarily winter ones. The article reflects the problems that arose during the implementation of the Committee’s resolutions, their overcoming, as well as the first actions to unite the efforts of the People’s Commissariats to solve priority tasks. It also provides information on the example of the Ukraine SSR about the loss of the entire light industry as a result of the occupation of virtually all the economic potential, which was to be replaced by enterprises in Central Russia and the eastern regions of the Soviet Union. The article presents the results of the work of the People’s Commissariat of Light Industry of the USSR for the 2nd half of 1941. The article is addressed to specialists in the field of the history of light industry, graduate students, undergraduates and students of higher educational institutions.

New Modes of Humanity and Everydayness in Gibson’s Cyberspace

The problem this article addresses is that we disregard the impact of cyberspace on our human development and everyday lives. We use cyberspace in our daily lives today through virtual work meetings and internet games. However, cyberspace can be more than a communication medium and game destination. It can be more than a matrix of networks in a science fiction story. Instead, cyberspace can be a space of human growth and where we experience our everyday lives. This article discusses the cyberspace described by William Gibson in his Sprawl trilogy, composed of the novels Neuromancer, Count Zero, and Mona Lisa Overdrive. The article shows how Gibson infuses cyberspace with everyday objects and situations. These everyday things enable the characters and readers to participate in a cyberspace that feels real and genuine. It depicts a cyberspace that is a new approach to being human and the emergence of a new everyday world. The research aims to show how cyberspace and our physical space are similar. It investigates how cyberspace contains a human dimension and human places. It examines how cyberspace can be as genuine as physical space. The research considers how cyberspace can provide a new everydayness and pathway for human living. From this research, the article hopes to show that cyberspace can be a place for human living in a world with fewer constraints. In this way, cyberspace can be an avenue for a new form of everydayness and greater human progress.

Selecting informative patients for phase 2 progressive trials in MS: Design considerations for phase 2 clinical trials in progressive MS.

While relapsing-remitting multiple sclerosis (MS) has many therapeutic options, progressive forms of MS remain largely untreatable. Phase 2 clinical trials are our main tool to advance new treatments for progressive MS. Given the complexities of progressive MS, it will likely require many phase 2 trials to improve its treatment. To conduct informative and efficient phase 2 trials, it is important that such trials are designed in a way that they can identify a successful treatment as quickly and with as few participants as possible. In this topical review, we discuss cohort selection, outcome selection, cohort enrichment, and dosing selection as strategies to optimize the efficiency of phase 2 clinical trials in progressive MS.

Molecular dynamics simulations of the effect of static electric field on progressive ice formation.

Ice accumulation under static electric fields presents a significant hazard to transmission lines and power grids. Contemporary computational studies of electrofreezing predominantly probed excessive electric fields (109 V/m) that are significantly higher than those typically encountered in proximity to transmission lines. To elucidate the influence of realistic electric fields (105 V/m) on ice crystallization, we run extensive molecular dynamics (MD) simulations across dual ice-water coexistence systems. Three aspects of work were accordingly examined. First, we investigated the influence of the effect of static electric fields, with a strength of 105 V/m, along three orthogonal axes on the phase transition during the encountered freezing and melting processes. Second, we established the mechanism of how the direction of an electric field, the initial ice crystallography, and the adjacent crystal planes influence the solidification process. Third, the results of our MD simulations were further post-processed to determine the dipole moment, radial distribution, and angle distribution resulting from the static electric field. Our results indicate that while weak electric fields do not cause complete polarization of liquid water molecules, they can induce a transition to a more structured ice-like geometry of the water molecules at the ice-water interphase region, particularly when applied perpendicular to the ice-water interphase. Notably, the interface adjacent to cubic ice exhibits a greater response to the electric fields than that adjacent to hexagonal ice. This is attributable to the intrinsic differences in their original hydrogen bonding networks.

Using MRI Texture Analysis Machine Learning Models to Assess Graft Interstitial Fibrosis and Tubular Atrophy in Patients with Transplanted Kidneys

Objective: Interstitial fibrosis/tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm to estimate the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1 January 2012 to 1 March 2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features that were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: A total of 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) were included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, the AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and a combined radiomic–clinical model, respectively. For IFTA ≥ 50%, the AUCs in training cohort were 0.89, 0.84, and 0.96, and in the test cohort, they were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and the combined radiomic–clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA > 50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.

Chemical and Structural Evolution of Rb2-2xK2xTi2O5 Layered Titanates When Exposed to Ambient Air.

In this report, we combine thermogravimetric analysis, X-ray diffraction, and infrared spectroscopy to investigate the chemical and structural evolution upon exposure of alkali titanates Rb2Ti2O5 and K2Ti2O5 and mixed compound Rb2-2xK2xTi2O5, for which 0 ≤ x ≤ 1, to the ambient atmosphere. We show that a complete solid solution exists between the potassium and rubidium end-members and that mixed compounds exhibit an intermediate behavior. When exposed to the ambient atmosphere, all compounds degrade, with the progressive formation of first hydrates and then bicarbonates and a much quicker degradation of the rubidium titanate than of the potassium titanate. On the contrary, we show that upon hydration in the absence of CO2, the crystal structure of K2Ti2O5 is more quickly impacted than that of Rb2Ti2O5. These observations should be useful for understanding the evolution of the functional properties of M2Ti2O5 alkali titanates upon aging in the ambient atmosphere, as well as for the optimization of their hydration-dependent properties.

Distraction osteogenesis in craniosynosotosis: technical note

Introduction: Craniosynostosis is a group of diseases whose main characteristic is the premature fusion of one or more cranial sutures. They can be subdivided into non-syndromic and syndromic. The posterior vault distraction osteogenesis (PVDO) has become the standard procedure for managing the intracranial hypertension of these patients. The objective of this paper is to report the experience of the Sobrapar Hospital (Campinas, Brazil) in treating and following up on syndromic craniosynostosis patients subjected to PVDO and highlight the lessons learned throughout this process. Methods: The medical records of the patients treated at the Sobrapar Hospital between 2013 and 2023 were reviewed. Results: The total of patients initially candidates to PVDO was 79, and 75 of them proceeded to the surgery. The mean age of surgery was 8,16 months old (ranging from 4 months to 12 years old). The length of stay ranged from 2 to 14 days, with a mean of 3,29 days. The distraction achieved ranged from 13 mm to 30 mm, with a mean distance of 23 mm. The postoperative complications were mostly cutaneous. CSF leak occurred in 3 patients. Conclusion: PVDO provides a progressive formation of a vascularized bone, its intracranial volume expansion is greater than the FOA, increasing the posterior fossa’s size (even when the craniotomy is supratorcular) and it improves Chiari’s symptoms, even when the radiologic abnormalities are not necessarily solved. A specialized and multidisciplinary team is essential to improving the success rates of the surgery.

The paradox of aging population and firm digital transformation in China

Although a number researchers have acknowledged that the aging population inhibits firm digital transformation, others find it promoting digital transformation in some firms. As the relevant literature to clarify such paradox is still scare, this paper wants to fill the gap regarding the labor cost theory, the capital-skill complementarity hypothesis, and the human capital externality theory. Based on the empirical tests of Chinese A-share listed companies from 2001 to 2022, this study detected a U-shaped relationship between the aging population and digital transformation. In terms of the institutional environment, higher marketization strengthens the U-shaped relationship by making the slopes on either side of it steeper. However, higher minimum wage levels weaken the U-shaped relationship. In terms of firm strategy, firms with stronger marketing capabilities strengthened the U-shaped relationship. However, firms with higher customer concentration weakened the U-shaped relationship. Overall, we enriched scholarly understanding of the impact of the aging population on digital transformation and demonstrated the dual potential impact of aging populations. Instead of assuming they are detrimental to the economy and society, positive contributions in the form of innovation and progress for companies can be detected.

Fatigue and depression influence the prevalence of anxiety in patients with multiple sclerosis.

There is scarce information in Middle-Eastern Europe regarding the prevalence of anxiety in patients with multiple sclerosis (pwMS) and its association with different clinical-demographic factors. We aimed to determine the prevalence of anxiety in Hungarian MS patients and to analyze associated factors. We evaluated 260 PwMS with the STAI-5 anxiety questionnaire. Fatigue (FIS), depression (BDI-II) and cognition (BICAMS) were also measured. Patients underwent standard neurological evaluations to evaluate Expanded Disability Status Scale (EDSS), and also measured the fine motor skills of the hand with the 9-hole peg test (9HPT), and the walking distance with the 25-foot walking test (T25FW). We identified 23.1% (N = 60) of the patients with anxiety (only state, trait or both forms concurrently). According to our two univariate, multivariable logistic regression analysis, fatigue and depression are strongly associated with both state and trait anxiety. In the absence of fatigue, the odds of trait anxiety are 82% lower (OR: 0.18; 95% CI: 0.06-0.53; p = 0.002), while in the case of pwMS without depression, the odds are reduced by 81% (OR: 0.19; CI95%= 0.07-0.51, p = 0.001). This association with fatigue (OR: 0.33; CI95%= 0.13-0.85, p = 0.021) and depression (OR: 0.14; CI95%=0.06-0.35; p < 0.001) can also be statistically verified on state anxiety. Importantly, a significant association with state anxiety was found in SPSM patients as well (OR: 34.94; CI95%=2.55-479.61; p = 0.008). Anxiety was strongly associated with fatigue, depression, and secondary progressive disease form. These results emphasize the burden of psychiatric morbidity in pwMS.

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies.

Integrated elemental analysis supports targeting copper perturbations as a therapeutic strategy in multiple sclerosis

Multiple sclerosis (MS) is a debilitating affliction of the central nervous system (CNS) that involves demyelination of neuronal axons and neurodegeneration resulting in disability that becomes more pronounced in progressive forms of the disease. The involvement of neurodegeneration in MS underscores the need for effective neuroprotective approaches necessitating identification of new therapeutic targets. Herein, we applied an integrated elemental analysis workflow to human MS-affected spinal cord tissue utilising multiple inductively coupled plasma-mass spectrometry methodologies. These analyses revealed shifts in atomic copper as a notable aspect of disease. Complementary gene expression and biochemical analyses demonstrated that changes in copper levels coincided with altered expression of copper handling genes and downstream functionality of cuproenzymes. Copper-related problems observed in the human MS spinal cord were largely reproduced in the experimental autoimmune encephalomyelitis (EAE) mouse model during the acute phase of disease characterised by axonal demyelination, lesion formation, and motor neuron loss. Treatment of EAE mice with the CNS-permeant copper modulating compound CuII(atsm) resulted in recovery of cuproenzyme function, improved myelination and lesion volume, and neuroprotection. These findings support targeting copper perturbations as a therapeutic strategy for MS with CuII(atsm) showing initial promise.

SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are largely used in the treatment of both relapsing remitting (RR) and progressive (PR) forms of MS. Although effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and a high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality; this, however, suggested the presence of differences in immune responses driven by age and disease severity.

Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH.

Lentinan attenuates allergic airway inflammation and epithelial barrier dysfunction in asthma via inhibition of the PI3K/AKT/NF-κB pathway

BackgroundAllergic asthma has been regarded as an inflammatory disease mediated by type 2 immunity. The treatment of progressive forms of asthma remains unsatisfactory despite substantial progress in drug development. Lentinan (LTN), a specific polysaccharide derived from Lentinus edodes, exhibits anti-inflammatory and immunomodulatory functions. Nevertheless, the effect and underlying mechanisms of Lentinan on asthma remain unclear. PurposeThis research investigated the regulatory role of Lentinan on allergic airway inflammation and epithelial barrier dysfunction in HDM (house dust mite)-induced asthma. Study designHDM-induced C57BL/6 mice received different dosages of Lentinan through intraperitoneal injections, to observe the effect of Lentinan against allergic airway inflammation and epithelial barrier dysfunction in asthma. MethodsMice were intranasally administered HDM extract solution on days 0, 1, 2 and on days 8 to 12, establishing the allergic asthma model. On days 8 to 12, mice were intraperitoneally administered varying doses of Lentinan (5/10/20mg/kg) 1h before HDM challenge. On day 14, samples were harvested for analysis. Cell counting, flow cytometry, ELISA, HE and PAS staining, IF staining, western blotting, RT-PCR, and bioinformatic analysis were conducted to delve into the underlying functions and mechanisms of Lentinan in asthma. ResultsOur study revealed that the treatment of Lentinan significantly ameliorated allergic airway inflammation and improved epithelial barrier dysfunction in experimental mice. Following Lentinan treatment, there was a significant reduction in eosinophil counts, accompanied by a diminished presence of type 2 cytokines. Reversal of epithelial barrier dysfunction after treatment was also observed. The therapeutic mechanism involved suppression of the PI3K/AKT/ NF-κB pathway. ConclusionOur research illuminated the protective role of Lentinan in allergic airway inflammation and impaired epithelial barrier, suggesting LTN could be an innovative and promising candidate for asthma treatment.

Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCβII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCβII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression.