The deficiency of Survival Motor Neuron (SMN) protein causes Spinal Muscular Atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in a SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma mem-brane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

Shape Memory Alloy (SMA) have emerged as a revolutionary material that holds the potential to change the design and construction methods of buildings and other structures. One of the most promising applications of SMAs in civil engineering is their use as reinforcements for steel structures. This paper presents the latest research progress, opportunities and challenges of SMA in the field of steel structural reinforcement, both in terms of basic components and applications. In terms of components, the construction forms and working mechanisms of Fe-SMA strips, SMA/CFRP composite patches and SMA dampers are introduced. On this basis, the application of SMA in steel structures reinforcement is introduced, and its effect is analyzed from three aspects: crack restoration, seismic retrofitting and structural strengthening. Finally, the results of the current research are summarized and the shortcomings are analyzed, hoping to provide a reference for the research of SMA in the field of steel structures reinforcement.

This paper aims to investigate the feasibility of strengthening the web opening in the shear zone of RC beams by using iron-based shape memory alloy (Fe-SMA) bars. To conduct this study, numerical analysis with ABAQUS software was employed. The research was divided into six groups of beams with web openings of different lengths (150, 300, and 450 mm), prestressing levels (0%, 30% and 60%), and reinforcement diameters (14, 18, and 22 mm) of Fe-SMA bars. The results show that the presence of web openings can cause a significant reduction in the cracking and ultimate loads of the beams, with reductions ranging from 11 to 50% and 36 to 48%, respectively. However, by adding pre-stressed Fe-SMA bars around small web openings (100×150 mm), the shear capacity of the beam is restored, and the beam exhibits behavior similar to solid beams. Additionally, activating the Fe-SMA bars by 30 and 60% resulted in almost similar cracking loads but improved load-carrying capacity of the beam with small openings by 12% and 9%, respectively, compared to the solid beam. The technique proposed for enhancing shear strength is most effective for beams with small (100×150 mm) and medium (100×300 mm) web openings as it can restore both the beam’s shear strength and stiffness. However, for beams with larger web openings (100×450 mm), the use of activated Fe-SMA beams can recover almost 90% of the solid beam's shear capacity. Furthermore, reinforcing small openings with Fe-SMA bars of different diameters enhances beam shear capacity and stiffness, while for larger openings, higher Fe-SMA reinforcement ratios could potentially restore the beam's full strength and stiffness. This study emphasizes the importance of strengthening web openings in RC beams, particularly in shear zones, and provides significant insights into how to strengthen beams with web openings, thereby contributing to developing safer structures. However, further laboratory experiments are recommended to validate, complement and extend the findings of this numerical study.

Slime Mould Algorithm (SMA) is a new swarm intelligence algorithm inspired by the oscillatory behavior of slime molds during foraging. Numerous researchers have widely applied SMA and its variants in various domains and proved its value by the experiments in literatures. In this paper a comprehensive survey on SMA is introduced, which is based on 130 articles visa Google-scholar between 2022 and July, 2023. Firstly, the theory of SMA is described. Secondly the improved SMA variants are provided and categorized according to the approach that they are applied with. Finally, it also discusses the main applications domains of SMA such as engineering optimization, energy optimization, machine learning, network, scheduling optimization, image segmentation and etc. This review presents some research suggestion for researcher who is interested in this algorithm.

In this systematic survey, an overview of non-conventional and soft-actuators is presented. The review is performed by using well-defined performance criteria with a direction to identify the exemplary applications in robotics. In addition to this, initial guidelines to measure the performance and applicability of soft actuators are provided. The meta-analysis is restricted to four main types of soft actuators: shape memory alloys (SMA), fluidic elastomer actuators (FEA), dielectric electro-activated polymers (DEAP) and shape morphing polymers (SMP). In exploring and comparing the capabilities of these actuators, the focus was on seven different aspects: compliance, topology, scalability-complexity, energy efficiency, operation range, performance and technological readiness level. The overview presented here provides a state-of-the-art summary of the advancements and can help researchers to select the most convenient soft actuators using the comprehensive comparison of the performance criteria.

Structural vibration induced by dynamic load or natural vibration is a nonnegligible factor in failure analysis. Based on vibrating boundary condition, impact resistance of shape memory alloy reinforced composites is investigated. In this investigation, modified Hashin’s failure criterion, Brinson’s model and visco-hyperelastic model are implemented into the numerical model to charactering the mechanical behavior of glass fiber/epoxy resin laminates, SMAs and interphase, respectively. First, fixed boundary condition is maintained in simulation to verify the accuracy of material parameters and procedures by comparing with experimental data. Then, a series of vibrating boundaries with different frequencies and amplitudes are applied during the simulation process to reveals the effect on impact resistances. The statistics of absorbed energy and contact force indicate that impact resistance of the composite under high frequency and large amplitude is lower than that under low frequency and small amplitude, and summarized by a mathematical expression.

Here we investigated the longer-term effect of Ncald-ASOs by additional i.c.v. bolus injection at PND28. Two weeks after injection of 500 µg Ncald-ASO in wild-type mice, NCALD was significantly reduced in brain and spinal cord and well tolerated. Next, we performed a double-blinded preclinical study combining low-dose SMN-ASO (PND1) with 2x i.c.v. Ncald-ASO or CTRL-ASO (100 µg at PND2, 500 µg at PND28). Ncald-ASO re-injection significantly ameliorated electrophysiological defects and NMJ denervation at 2 months. Moreover, we developed and identified a nontoxic and highly efficient human NCALD-ASO that significantly reduced NCALD in hiPSCs-derived MNs. This improved both neuronal activity and growth cone maturation of SMA MNs, emphasizing the additional protective effect of NCALD-ASO treatment.

The work at hand focuses on an adaptive system aimed at improving the soundproof performance of car door seals at specific working regimes (cruise), without interfering with the conventional open-closure operations. The idea addresses the necessity of increasing the seal effectiveness, jeopardized by aerodynamic actions more and more important as the speed increase, generating a pressure difference between the internal and the external filed, in the direction of opening the door. To recover this effect, an expanding mechanism was integrated within the seal cavity, driven by an SMA actuator. The material was activated (heated) by Joule effect; its compactness, intrinsic of smart materials, contributed to arrive to a final system characterized by a high level of integrability (expanding cells). In this paper, the development process is described together with the verification activity, aimed at proving the functionality of the realized device. Starting from the industrial requirements, the most appropriate solution was identified highlighting the working principle and the main design parameters involved. Then, the envisaged system was designed and its executive digital mock up (CAD) was released. Prototyping and laboratory validation showed the reliability of the numerical models and the associated predictions. On this basis, the integration task within the actual reference car was faced. To demonstrate the isolation effect of the proposed system, an experimental campaign was finally organized in an anechoic room, achieving significant results on the concept value.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Despite the fact that SMA restrainers exhibit a superelastic strain capacity of 7%, this capacity appears inadequate for isolated bridges due to the typically greater than 20cm relative dis-placements between girders during intense seismic events. In order to perform such a stroke, a SMA restrainer of greater than 3 metres in length might be required. In order to reduce the length of restrainers, a novel honeycomb damper constructed from superelastic shape memory alloy (SMA) is proposed. The proposed device, denoted as the superelastic SMA honeycomb damper (SHD), is comprised of steel plates to prevent the SMA plane from collapsing and superelastic SMA honeycomb to provide self-centering capability. By incorporating the large strain capacity of SMA and the geometrically nonlinear deformation of honeycomb structures, SHD has been developed to satisfy the requirements of bridge restrainers with large strokes. It is capable of functioning as a restrainer and energy dissipation device when subjected to dynamic tension and compression loads. The SHD was initially investigated from a theoretical perspective. Following this, a mul-ti-cell SHD specimen was manufactured. The specimen underwent axial tensile and compressive experiments in order to examine the mechanical properties of SHDs. Finally, experimental results were investigated through numerical simulation analyses of the SHDs using a three-dimensional high-fidelity finite element model. Additionally, a method for enhancing SHD was proposed. The findings indicate that SHD is capable of exhibiting superior self-centering capability and sta-ble hysteretic responses when subjected to earthquakes.

The shape memory alloys belong to the smart materials thanks to their thermomechanical proprieties' reply to thermal or to mechanical loading. These materials can change shape, stiffness, displacement, natural frequency, and many mechanical characteristics in response to stress or to heat such as conduction, convection or radiation. However, heating by convection or conduction are the most useful and studied methods unlike radiation. Therefore, this paper aims to study the radiation effect on the shape memory alloy behavior

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.

Mining for resources extraction may lead to several geological and associated environmental changes due to ground movements, collision with mining cavities and deformation of aquifers. Geological changes may continue in a reclaimed mine area, and the deformed aquifers may entail a breakdown of substrates and an increase in ground water tables, which may cause surface area inundation. Consequently, a reclaimed mine area may experience surface area collapse, i.e. subsidence, and degradation of vegetation health. Thus, monitoring short-term landscape dynamics in a reclaimed mine area may provide important information on the long-term geological and environmental impacts of mining activities. We studied landscape dynamics in Kirchheller Heide, Germany, which experienced extensive soil movement due to longwall mining without stowing, using Landsat imageries between 2013 and 2016. A Random Forest image classification technique was applied to analyse land-use and land-cover dynamics and the growth of wetland areas was assessed using a Spectral Mixture Analysis (SMA). We also analyzed the changes in vegetation health using a Normalized Difference Vegetation Index (NDVI). We observed a 19.9% growth of wetland area within the four years with 87.2% of growth in the coverage of two major waterbodies in the reclaimed mine area. NDVI values indicate that 66.5% of the vegetation of the study area was degraded due to changes in ground water tables and surface flooding. Our results inform environmental management and mining reclamation authorities about the subsidence spots and priority mitigation areas from land surface and vegetation degradation in Kirchheller Heide.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

The current study assessed the influence of Anti Stripping Agents (ASA), Ground Tire Rubber (GTR) and waste polyethylene terephthalate (PET) on performance behavior of binder and Stone Matrix Asphalt (SMA) mixtures. Through this paper, the 85/100 penetration grade bitumen was utilized as original bitumen. Also, three liquid ASA’s (ASA (A), ASA (B), ASA (C)) were used as a mixture modifier. For this purpose, softening point, penetration, rotational viscosity, Dynamic Shear Rheometer, Multi Stress Creep Recovery (MSCR) and Linear Amplitude Sweep (LAS) tests were implemented to investigate the rheological properties of modified bitumen. For evaluating the behavior of modified mixtures several tests such as; Resilient Modulus, Tensile Strength, dynamic creep, wheel track and four-point beam fatigue tests were implemented. Based on MSCR test results, utilization of mentioned polymers enhanced the elasticity of bitumens and therefore the permanent deformation resistance of binders increases. Also by the addition of PET percentage, the rutting resistance improves. Results indicated that utilization of ASAs, PET and Crumb Rubber (CR) enhance the Resilient Modulus (Mr), Indirect Tensile Strength (ITS), rutting resistance, fatigue life and Fracture Energy (FE) of asphalt mixtures. Also based on results, modification of binder by PET/CR with a ratio of 50%/50% and ASA (B) have the highest fatigue life which indicates that this mixture has highest resistance against fatigue cracking.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy