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Virtual Reality applications are predicted to create a paradigm shift in education, but there is little empirical evidence of their educational value. Virtual Reality affordances to support language learning have not yet been realized. This quasi-experimental study investigated the effect of a Virtual Reality application on foreign language learning and compared engagement, engrossment, and immersion between two versions of the application (Virtual Reality and mobile). Twenty experimental group undergraduate students used a head-mounted Virtual Reality display and twenty control group students used a mobile application for learning Italian as a foreign language. Data sources included: (a) a 10 open-ended questions pre-test and post-test measuring vocabulary skills, and (b) a validated questionnaire with 21 seven-point Likert scale items measuring engagement, engrossment, and immersion. Findings revealed a statistically significant difference in the experimental group students' vocabulary performance when students' pre-test and post-test scores were compared. Engagement, engrossment, and immersion received relatively high scores by Virtual Reality participants. The study did not find a statistically significant difference between the two conditions. The study provides preliminary empirical data indicating that Virtual Reality applications can be both effective and engaging for language learning, even though they were not found to be superior to mobile applications.

Abstract In the model manganese perovskites La1−x Ca x MnO3, several important phenomena have been observed, including ferromagnetic metallic/insulating states, colossal magnetoresistance effects, and charge- and orbital-ordered states. In the past, only compounds with x = 1/2, 2/3 and 3/4 and an insulating ground/antiferromagnetic state have been studied. To fully understand the crystal and electronic structures of these materials, it is important to study compounds with doping levels in the range of 0.5

3D virtual prototyping for garment development, although not much exploited and appreciated by the clothing industry in the early days of its appearance two decades ago, has now been explored (research-wise) extensively especially in the pandemic period and its impact on the whole supply chain of garments and fashion products. This virtual prototype which allows the company to visualize the status and condition of a clothing product that may be thousands of kilometers away, providing insights into how products can be better designed, manufactured, operated and serviced before companies invest in physical prototypes and assets, is often called digital twin. At the same time, laser-cut as a creative design technique on clothing materials have emerged in recent times, as fashion moguls are seeing the benefits that the technology presents. Laser cut technology with its benefits of accuracy, speed, precision, applicability in various materials, flexibility in geometry, interoperability with other systems like CAD/CAM and CIM, sustainability in resources and source of inspiration for several upcoming designers, provides an excellent approach for creating bridges between the past, the present and the future in history of fashion design. The aim of this paper was to provide a decision-making framework for the selection of an effective digital twinning process with the use of two different 3D virtual prototyping tools. For this purpose, a methodological framework is proposed which guides the creator according to the final use of the digital garment twin: evaluation of actual fit and actual representation of the produced physical, or as a shared digital asset for an exclusive digital environment.

Heart failure (HF) and chronic kidney disease (CKD) are associated with high mortality. In both disorders, impaired iron homeostasis, mostly in the form of a functional iron deficiency, is a frequent co-morbidity. In HF, functional iron deficiency and management by i.v. iron supplementation have been proven to affect both prognosis and functional capacity. In the same context, iron supplementation is routine for the adequate management of renal anemia in CKD. In numerous recent studies in HF and in CKD, sodium–glucose transporter 2 (SGLT2) inhibitor treatment has been proven to significantly reduce mortality. Furthermore, the same trials showed that these drugs alleviate iron deficiency and anemia. These effects of SGLT2 inhibitors may be due to an amelioration of inflammation with reduced interleukin-6 (IL-6) and to an enhancement of autophagy with increased sirtuin 1 (SIRT1), both associated with modified production of hepcidin and enhanced ferritinophagy. However, the exact pathogenic basis of the beneficial SGLT2 inhibitor action is not fully elucidated. Nevertheless, effects on iron homeostasis might be a potential explanatory mechanism for the powerful SGLT2 inhibitors’ cardiovascular and renal outcome benefits. In addition, the interaction between iron supplementation and SGLT2 inhibitors and its potential impact on prognosis remains to be clarified by future studies. This review represents a significant effort to explore the complex relationships involved, seeking to elucidate the intricate mechanisms by which SGLT2 inhibitors influence iron homeostasis.

Abstract Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prolonged activation of ASIC1a induces necroptosis in GSCs is unknown. Here we used a tumorsphere formation assay to show that slight acidosis (pH 6.6) induces necrotic cell death in a manner that was sensitive to the necroptosis inhibitor Nec-1 and to the ASIC1a antagonist PcTx1. In addition, genetic knockout of ASIC1a rendered GSCs resistant to acid-induced reduction in tumorsphere formation, while the ASIC1 agonist MitTx1 reduced tumorsphere formation also at neutral pH. Finally, a 20 amino acid fragment of the ASIC1 C-terminus, thought to interact with the necroptosis kinase RIPK1, was sufficient to reduce the formation of tumorspheres. Meanwhile, the genetic knockout of MLKL, the executive protein in the necroptosis cascade, did not prevent a reduction in tumor sphere formation, suggesting that ASIC1a induced an alternative cell death pathway. These findings demonstrate that ASIC1a is a death receptor on GSCs that induces cell death during prolonged acidosis. We propose that this pathway shapes the evolution of a tumor in its acidic microenvironment and that pharmacological activation of ASIC1a might be a potential new strategy in tumor therapy.

Diabetic kidney disease (DKD) is a serious microvascular complication of type 2 diabetes mellitus (T2DM). Despite the numerous genetic loci that have been associated with the disease in T2DM, the genetic architecture of DKD remains unclear until today. In contrast to SERPINE1, the contribution of SERPINB2 has not been examined in DKD. Therefore, we conducted the first genetic association study of SERPINB2 to elucidate its role in DKD. In total, the study involved 197 patients with DKD, 155 patients with T2DM without microvascular complications (diabetic kidney disease, diabetic retinopathy, and diabetic neuropathy), and 246 healthy controls. The generalized odds ratio (ORG) was calculated to estimate the risk on DKD development. The present association study regarding SERPINB2 SNPs (rs4941230, rs3819335, rs13381217, rs6140) did not reveal any significant association between SERPINB2 variants and DKD. Additional studies in other populations are necessary to further investigate the role of this gene in the progression of diabetes mellitus and development of DKD. [ABSTRACT FROM AUTHOR]

Ischemia‐reperfusion (I‐R) injury is the most common cause of acute kidney injury. In experiments involving primary human renal proximal tubular epithelial cells (RPTECs) exposed to anoxia‐reoxygenation, we explored the hypothesis that mitochondrial malate dehydrogenase‐2 (MDH‐2) inhibition redirects malate metabolism from the mitochondria to the cytoplasm, towards the malate‐pyruvate cycle and reversed malate‐aspartate shuttle. Colorimetry, fluorometry, and western blotting showed that MDH2 inhibition accelerates the malate‐pyruvate cycle enhancing cytoplasmic NADPH, thereby regenerating the potent antioxidant reduced glutathione. It also reversed the malate‐aspartate shuttle and potentially diminished mitochondrial reactive oxygen species (ROS) production by transferring electrons, in the form of NADH, from the mitochondria to the cytoplasm. The excessive ROS production induced by anoxia‐reoxygenation led to DNA damage and protein modification, triggering DNA damage and unfolded protein response, ultimately resulting in apoptosis and senescence. Additionally, ROS induced lipid peroxidation, which may contribute to the process of ferroptosis. Inhibiting MDH‐2 proved effective in mitigating ROS overproduction during anoxia‐reoxygenation, thereby rescuing RPTECs from death or senescence. Thus, targeting MDH‐2 holds promise as a pharmaceutical strategy against I‐R injury. [ABSTRACT FROM AUTHOR]

In the work described herein, the spin relaxation properties of the mononuclear tetrahedral S=2 [Fe{(SPiPr2)2N}2] complex (1) were studied by employing static and dynamic magnetic measurements at liquid helium temperatures. In the absence of an external direct current (DC) magnetic field, 1 exhibits fast magnetization relaxation. However, in the presence of external magnetic fields of a few kOe, slow relaxation is induced as monitored by alternating current (AC) magnetic susceptibility measurements up to 10 kHz, in the temperature range 2–5 K. Analysis of the temperature dependence of the corresponding relaxation time reveals contributions by Quantum Tunnelling of Magnetization, and the Direct and Orbach processes in the magnetization relaxation mechanism of 1. The energy barrier, Ueff, of the Orbach process, as determined by this analysis, is compared with that related to the zero‐field splitting parameters of 1 which were previously determined by high‐ frequency and ‐field electron paramagnetic resonance and Mössbauer spectroscopies. [ABSTRACT FROM AUTHOR]

The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09–4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545–11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.

Besides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious outcomes of the above pathways, apoptosis, senescence, or epithelial-to-mesenchymal transition (EMT) were evaluated. Albumin caused reactive oxygen species (ROS) overproduction and protein modification, and a UPR assessed the level of crucial molecules involved in this pathway. ROS also induced a DDR evaluated by critical molecules involved in this pathway. Apoptosis ensued through the extrinsic pathway. Senescence also occurred, and the RPTECs acquired a senescence-associated secretory phenotype since they overproduced IL-1β and TGF-β1. The latter may contribute to the observed EMT. Agents against endoplasmic reticulum stress (ERS) only partially alleviated the above changes, while the inhibition of ROS upregulation prevented both UPR and DDR and all the subsequent harmful effects. Briefly, albumin overload causes cellular apoptosis, senescence, and EMT in RPTECs by triggering UPR and DDR. Promising anti-ERS factors are beneficial but cannot eliminate the albumin-induced deleterious effects because DDR also occurs. Factors that suppress ROS overproduction may be more effective since they could halt UPR and DDR.

The enantiomerically pure Schiff base ligands H2L‐S and H2L‐R yield chiral heterometallic dodecanuclear complexes of the form [Cu8Ln4(OH)8(OMe)4(O2CBut)8(L‐S or L‐R)4(H2O)4] where LnIII=Gd (1S), Tb (2S), Dy (3S, 3R), Ho (4S, 4R), Er (5S) or Y (6S, 6R) and H2L=(S or R)‐2‐{[(1‐hydroxypropan‐2‐yl)imino]methyl}‐6‐methoxyphenol. The complexes are isomorphous and crystallize in the non‐centrosymmetric polar space group C2 in enantiomeric conformation. The chirality of the Schiff base ligands originates from the respective S‐ or R‐ enantiomer of 2‐aminopropan‐1‐ol, is imparted to the complexes and to the crystals that belong to non‐centrosymmetric space group. The chirality and enantiomeric conformation of all complexes are retained in dmso solutions as confirmed by Circular Dichroism spectra which consist of mirror images, expected for enantiomeric pairs. All complexes consist of four distorted cubane‐like subunits [Cu2Ln2(μ3‐OH)2(μ3‐OMe)(μ3‐OR)], which share the LnIII ions and result in a cyclic distorted tetragonal arrangement; each edge of the {LnIII4} quadrilateral is occupied by two μ‐OH− ions that further bridge to a CuII ion. Magnetic susceptibility measurements revealed ferromagnetic interactions for 3S with LnIII=Dy and antiferromagnetic interactions for all other complexes. AC susceptibility data of 3S under 1 kOe external dc field indicate slow magnetic relaxation phenomena below 2 K. [ABSTRACT FROM AUTHOR]

Fast growing solid tumors are frequently surrounded by an acidic microenvironment. Tumor cells employ a variety of mechanisms to survive and proliferate under these harsh conditions. In that regard, acid-sensitive membrane receptors constitute a particularly interesting target, since they can affect cellular functions through ion flow and second messenger cascades. Our knowledge of these processes remains sparse, however, especially regarding medulloblastoma, the most common pediatric CNS malignancy. In this study, using RT-qPCR, whole-cell patch clamp, and Ca2+-imaging, we uncovered several ion channels and a G protein-coupled receptor, which were regulated directly or indirectly by low extracellular pH in DAOY and UW228 medulloblastoma cells. Acidification directly activated acid-sensing ion channel 1a (ASIC1a), the proton-activated Cl− channel (PAC, ASOR, or TMEM206), and the proton-activated G protein-coupled receptor OGR1. The resulting Ca2+ signal secondarily activated the large conductance calcium-activated potassium channel (BKCa). Our analyses uncover a complex relationship of these transmembrane proteins in DAOY cells that resulted in cell volume changes and induced cell death under strongly acidic conditions. Collectively, our results suggest that these ion channels in concert with OGR1 may shape the growth and evolution of medulloblastoma cells in their acidic microenvironment. [ABSTRACT FROM AUTHOR]