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Living cells regulate the dynamics of developmental events through interconnected signaling systems that activate and deactivate inert precursors. This suggests that similarly, synthetic biomaterials could be designed to develop over time by using chemical reaction networks to regulate the availability of assembling components. Here we demonstrate how the sequential activation or deactivation of distinct DNA building blocks can be modularly coordinated to form distinct populations of self-assembling polymers using a transcriptional signaling cascade of synthetic genes. Our building blocks are DNA tiles that polymerize into nanotubes, and whose assembly can be controlled by RNA molecules produced by synthetic genes that target the tile interaction domains. To achieve different RNA production rates, we use a strategy based on promoter nicking and strand displacement. By changing the way the genes are cascaded and the RNA levels, we demonstrate that we can obtain spatially and temporally different outcomes in nanotube assembly, including random DNA polymers, block polymers, and as well as distinct autonomous formation and dissolution of distinct polymer populations. Our work demonstrates a way to construct autonomous supramolecular materials whose properties depend on the timing of molecular instructions for self-assembly, and can be immediately extended to a variety of other nucleic acid circuits and assemblies.

Objectives: The in vivo assay is a key step in the development of a new bioactive compound as a lead drug structure. Based on importance of α-glucosidase inhibitors in the control of blood glucose level (BGL) in diabetes, in the present work, 3-amino-1-(4-chlorophenyl)-12-oxo-11,12-dihydro-1H-benzo[h]pyrano[3,2-c]quinoline-2-carbonitrile (ACODDHBPQC) that showed excellent inhibitory activity on the yeast form of α-glucosidase was selected for in vivo anti-diabetic assay. Methods: The in vivo anti-diabetic and anti-lipidemic effects of this synthetic compound were evaluated using by a streptozotocin (STZ)-induced diabetic Wistar rat model. In silico docking study of ACODDHBPQC was performed by Atodock tools and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of this compound was predicted by PreADMT online software. Results: The obtained results revealed that selected compound ACODDHBPQC showed a significant anti-diabetic effect on diabetic rats. In vivo anti-lipidemic assay also demonstrated that ACODDHBPQC had favorable effects on cholesterol and LDL levels. Furthermore, in silico studies showed that ACODDHBPQC interacted with key residues of the α-glucosidase active site and had good pharmacokinetic and toxicity properties. Conclusion: In summary, anti-hyperglycemic effects of ACODDHBPQC was confirmed by in vivo study. However, more evaluations are needed to introduce ACODDHBPQC as a lead drug compound. [ABSTRACT FROM AUTHOR]

Mammalian prions are neurotropic pathogens formed from PrPSc assemblies, a misfolded variant of the host‐encoded prion protein PrPC. Multiple PrPSc conformations or strains self‐propagate in host populations or mouse models of prion diseases, exhibiting distinct biological and biochemical phenotypes. Constrained interactions between PrPSc and PrPC conformations confer species specificity and regulate cross‐species transmission. The pathogenicity of fibrillar assemblies derived from bacterially expressed recombinant PrP (rPrP) has been instrumental in demonstrating the protein‐only nature of prions. Yet, their ability to encode different strains and transmit between species remains poorly studied, hampering their use in exploring structure‐to‐strain relationships. Fibrillar assemblies from rPrP with hamster, mouse, human, and bovine primary structures were generated and tested for transmission and adaptation in tg7 transgenic mice expressing hamster PrPC. All assemblies, except the bovine ones, were fully pathogenic on the primary passage, causing clinical disease, PrPSc brain deposition, and spongiform degeneration. They exhibited divergent adaptation processes and strain properties upon subsequent passage. Assemblies of hamster origin propagated without apparent need for adaptation, those of mouse origin adapted abruptly, and those of human origin required serial passages for optimal fitness. Molecular analyses revealed the presence of endogenously truncated PrPSc species in the resulting synthetic strains that lack the 90–140 amino acid region considered crucial for infectivity. In conclusion, rPrP assemblies provide a facile means of generating novel prion strains with adaptative/evolutive properties mimicking genuine prions. The PrP amino acid backbone is sufficient to encode different strains with specific adaptative properties, offering insights into prion transmission and strain diversity. [ABSTRACT FROM AUTHOR]

Pasar Raya Padang, located in a seismically active area with a history of liquefaction from the 30 September 2009 earthquake, requires a detailed liquefaction potential analysis. This study aims to determine the influence of earthquake significant duration on ground motions at the site and to address the limitations of the commonly used simplified method. Four synthetic ground motion variations were generated to reflect the site characteristics and used in non-linear numerical analyses to calculate safety factors. The results indicate that both short and long-duration earthquakes, particularly those with late maximum peak ground accelerations, significantly increase the pore water pressure ratio by 20-50%. Short-duration earthquakes with early peak ground accelerations result in higher cyclic stress ratios. Liquefaction potential was identified at depths of 12-20 meters. The study concludes that short-duration earthquakes pose a higher liquefaction risk than long-duration events. The results highlight the critical role of accurately selecting ground motions for risk assessment, which is essential for mitigating liquefaction risk in future construction projects. [ABSTRACT FROM AUTHOR]

Nicotine is a chiral alkaloid; nitrogen-containing organic compound that occurs naturally. (S)-nicotine is extracted from Tobacco plants and used as the key addictive ingredient in many smoking products. Synthetic nicotine has gained the interest of many smoking product manufacturers over the last few decades due to the ease and low cost of manufacturing. Another claimed advantage of synthetic nicotine is the absence of genotoxic impurities that form during the extraction process of nicotine. These impurities are other plant alkaloids, phenolic compounds, and heavy metals. Additionally, the U. S. FDA has implemented new regulations on the quality control of synthetic nicotine. However, only a very few research articles have been published on assessing the complete impurity profile of synthetic nicotine. Therefore, the need to know the composition difference between tobacco-extracted nicotine vs. synthetic nicotine is highly necessary. In this research study, the impurity profile of thirteen different lots of synthetic nicotine was compared with fourteen lots of nicotine extracted from plants using in-house analytical methods. First, the samples were tested for other alkaloids and phenols by reversed-phase High-Performance Liquid Chromatography (HPLC). Second, the chiral purity was analyzed by normal phase HPLC. Third, lead and arsenic content were tested by atomic absorption and fluorescence spectrometry. Fourth, nicotine-specific nitrosamines were tested by LC-MS. The reversed phase HPLC data suggested similar quantities of total impurities in both synthetic and tobacco-extracted nicotine (0.1%). However, synthetic nicotine lacks some impurities such as cotinine, nornicotine, and nicotine-N-oxide. Additionally, the synthetic nicotine lots used in this study have high enantiomeric purity similar to the tobacco-extracted nicotine. [ABSTRACT FROM AUTHOR]

Some patients with intracranial aneurysms (IAs) cannot undergo three-dimensional computed tomography angiography (3D-CTA) or digital subtraction angiography due to contraindications to contrast agents or radiation. Time-of-flight magnetic resonance angiography (TOF-MRA) offers a contrast-free alternative but lacks cranial bone detail critical for surgical planning. This study evaluates the feasibility of using 3D Slicer to fuse TOF-MRA with thin-section CT images to generate synthetic images resembling CTA for surgical clipping planning. This prospective study included 22 patients with unruptured IAs and 8 with ruptured IAs undergoing aneurysm clipping surgery (≥3 mm). TOF-MRA and CT/3D-CTA scans were fused using 3D Slicer. Neuroradiologists and neurosurgeons independently assessed 3D-CTA and synthetic TOF-MRA-CT images for aneurysm detection rates, morphology, and dimensions. Evaluation metrics included dice similarity coefficient and 95% Hausdorff distance. Evaluation of aneurysm detection rates, morphology, and dimensions showed no significant differences between synthetic TOF-MRA-CT fusion images and 3D-CTA (all P > 0.05). Neuroradiologist assessments revealed strong concordance in aneurysm morphology between synthetic TOF-MRA-CT fusion images and 3D-CTA (κ = 0.867, P < 0.001). The dice similarity coefficient (0.937 ± 0.012) and Hausdorff distance (4.54 ± 0.26) indicated a high degree of image overlap between synthetic TOF-MRA-CT fusion images and 3D-CTA. Surgeons rated the consistency of aneurysm morphology between synthetic TOF-MRA-CT fusion images and intraoperative findings as strongly concordant (κ = 0.873, P < 0.001). Synthetic TOF-MRA-CT fusion images closely match 3D-CTA for ≥3 mm aneurysms, demonstrating comparable diagnostic and surgical clipping planning effectiveness. They represent a promising alternative for personalized preoperative planning, particularly when contrast agents are contraindicated. [ABSTRACT FROM AUTHOR]

The aim of this study was to demonstrate a case of aorto-carotid bypass in a patient with carotid artery stenosis as a reasonable and necessary method for preventing ischemic stroke. The study was conducted at the University Hospital Center “Mother Teresa” (QSUT), Tirana. A 63-year-old patient with atherosclerotic arteriopathy and hypertension presented with episodes of dizziness and syncope. Doppler echocardiography revealed an increase in blood flow velocity in the right and left carotid arteries by more than 2.5 times. Computed tomography angiography visualised stenosis of the right and left common carotid arteries, stenosis of the brachiocephalic trunk at the beginning, and occlusion of the left subclavian artery. Performed revascularization of the common carotid arteries using a bifurcated 14×7 mm Dacron graft. The proximal end of the graft was anastomosed to the ascending aorta, and the distal ends were connected to both common carotid arteries. Follow-up Doppler echocardiography showed normalization of blood flow velocity in the carotid arteries. The patient’s neurological symptoms completely disappeared. The patient was discharged without complications after 10 days. The method of resolving complex multisegmental stenosis by aorto-carotid bypass ensures optimal perfusion of the brain and is proposed for use in appropriate conditions for the prevention of ischemic stroke.

Intermediate wheatgrass (IWG) is a perennial grass that produces nutritious grain while offering substantial ecosystem services. Commercial varieties of this crop are mostly synthetic panmictic populations that are developed by intermating a few selected individuals. As development and generation advancement of these synthetic populations is a multiyear process, earlier synthetic generations are tested by the breeders and subsequent generations are released to the growers. A comparison of generations within IWG synthetic cultivars is currently lacking. In this study, we used simulation models and genomic prediction to analyze population differences and trends of genetic variance in 4 synthetic generations of MN-Clearwater, a commercial cultivar released by the University of Minnesota. Little to no differences were observed among the 4 generations for population genetic, genetic kinship, and genome-wide marker relationships measured via linkage disequilibrium. A reduction in genetic variance was observed when 7 parents were used to generate synthetic populations while using 20 led to the best possible outcome in determining population variance. Genomic prediction of plant height, free threshing ability, seed mass, and grain yield among the 4 synthetic generations showed a few significant differences among the generations, yet the differences in values were negligible. Based on these observations, we make 2 major conclusions: (1) the earlier and latter synthetic generations of IWG are mostly similar to each other with minimal differences and (2) using 20 genotypes to create synthetic populations is recommended to sustain ample genetic variance and trait expression among all synthetic generations. [ABSTRACT FROM AUTHOR]

Analytical or synthetic knowledge is widely considered beneficial for eco‐innovation (EI). For a firm, analytical and synthetic knowledge can be acquired externally through collaboration with various partners or generated internally through R&D and other internal firm activities. However, evidence supporting the assumption that both forms of knowledge are complementary and that "doing more of all" will benefit EI is unclear. We found that external analytical and synthetic knowledge and internal analytical and synthetic knowledge all positively affect EI, with internal analytical being the most prominent. However, combining analytical and synthetic knowledge may not be beneficial for EI. The interaction between analytical and external synthetic knowledge is generally substitutive. We found a particularly significant substitutive effect between internal analytical and internal synthetic knowledge, as well as between internal analytical and external synthetic knowledge. In short, we found little evidence of complementarity between analytical and synthetic knowledge, regardless of where it is acquired from. These findings advise caution to firm managers and policymakers who are considering strategies to combine different forms of knowledge from different sources to successfully achieve EI goals. [ABSTRACT FROM AUTHOR]

In recent years, the exploration of natural compounds for their therapeutic potential has gained considerable attention, with xanthones emerging as promising candidates due to their diverse biological activities including anti-inflammatory properties. This comprehensive review delves into the synthesis and evaluation of synthetic xanthone derivatives as potential anti-inflammatory agents. The review commences by introducing the structural characteristics and chemical diversity of synthetic xanthone derivatives, highlighting the various methods used to synthesize them. It then delves into the mechanisms underlying the anti-inflammatory effects of synthetic xanthone derivatives, focusing on their interactions with key pathways involved in inflammation. Furthermore, the review explores the relationships between the structure of synthetic xanthones and their anti-inflammatory potential, shedding light on critical structural elements responsible for their efficacy. In summary, this review consolidates our existing knowledge about synthetic xanthone derivatives as a class of compounds with remarkable anti-inflammatory properties. It underscores the importance of further research to fully understand how they work, improve their pharmacological properties, and assess their clinical benefits. Synthetic xanthone derivatives show immense promise in the search for new anti-inflammatory therapeutics, making them a compelling subject for future drug development endeavors. [ABSTRACT FROM AUTHOR]

Today, the transformation of polymers into useful structures for the human body in medical field has been an interesting subject that affected everyone. Synthetic polymers have a wide range of uses in the health sector such as coating, cardiovascular, orthodontic surgery, tissue engineering, implant, and drug carrier with the development of technology. These polymers are known as polymers with various characteristics and applications artificially synthesized in accordance with chemical and thermodynamic laws. The polymers in health sector have a share of 41% in drug and release studies, 18% in treatment with therapy applications, 10% in vaccine production, 31% in studies on new approaches in this field. Synthetic polymers have ability to be produced cheaply and easily in large quantities. In this study, synthetic polymers such as polyethylene glycol, polyvinyl alcohol, polyurethane, polyolefin, polytetrafluoroethylene, silicone, polyvinyl chloride, poly-methyl methacrylate, polyester, polyamide and poly-lactic acid were investigated and details regarding the applications with explications of polymers were provided. It was seen that synthetic polymers could be evaluated in treatment of cancer and chronic diseases by determining the most appropriate methods and techniques with biocompatible, biodegradable, non-toxic materials. [ABSTRACT FROM AUTHOR]

Acrylamide (AM), 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and dimethyl-diallyl ammonium chloride (DMDAAC) as monomers to prepare amphoteric polyacrylamide, the salt resistance was tested. The result showed that qualitative analysis by infrared spectroscopy and nuclear magnetic resonance confirmed that the synthesized product was the target product, and AMPAM can maintain a viscosity of more than 10 mPa ⋅ s in 20 000 mg/L NaCl solution and 10 000 mg/L CaCl2 solution. Scanning elec-tron microscopy was used to observe the changes in the microscopic morphology of AMPAM solution with 0.5% concentration at different salinity. Due to the serious weakening of intermolecular attraction and repulsion, the molecular chains began to converge and curl, forming a large number of molecular clusters and eventually forming a complete block structure. At this time, the viscosity of the solution changed little and gradually became stable. [ABSTRACT FROM AUTHOR]

Sirtuins are a group of enzymes known as class III histone deacetylases that catalyze the deacetylation reaction and are presented across various species. In humans, they exhibit seven isoforms known as SIRT1–7, localize in distinctive cellular compartments, the nucleus (SIRT1, 6, 7), cytoplasm (SIRT2), and mitochondria (SIRT3, 4, 5). They play crucial roles in metabolism, DNA repair, and rRNA transcription. As research on sirtuins has expanded, there has been increased interest in identifying sirtuin modulators that may hold therapeutic implications in various diseases. Despite the identification of numerous sirtuin modulators, only few have entered clinical trials due to selectivity and safety concerns. Hence, subsequent research is needed to understand their mechanisms and ensure their safety profiles. This review summarizes experimental data and the status of sirtuin modulators reported from 2013 to current, aiming to contribute to the advancement of sirtuin modulation research and the identification of promising candidates for future development. [ABSTRACT FROM AUTHOR]

Synthesis prediction is a key accelerator for the rapid design of advanced materials. However, determining synthesis variables such as the choice of precursor materials is challenging for inorganic materials because the sequence of reactions during heating is not well understood. In this work, we use a knowledge base of 29,900 solid-state synthesis recipes, text-mined from the scientific literature, to automatically learn which precursors to recommend for the synthesis of a novel target material. The data-driven approach learns chemical similarity of materials and refers the synthesis of a new target to precedent synthesis procedures of similar materials, mimicking human synthesis design. When proposing five precursor sets for each of 2654 unseen test target materials, the recommendation strategy achieves a success rate of at least 82%. Our approach captures decades of heuristic synthesis data in a mathematical form, making it accessible for use in recommendation engines and autonomous laboratories.

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.

Synthetic biology enables the design of gene networks to confer specific biological functions, yet it remains a challenge to rationally engineer a biological trait as complex as longevity. A naturally occurring toggle switch underlies fate decisions toward either nucleolar or mitochondrial decline during the aging of yeast cells. We rewired this endogenous toggle to engineer an autonomous genetic clock that generates sustained oscillations between the nucleolar and mitochondrial aging processes in individual cells. These oscillations increased cellular life span through the delay of the commitment to aging that resulted from either the loss of chromatin silencing or the depletion of heme. Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally designed gene circuits that slow aging.

The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions. Here we report the discovery and characterization of CtdP, a member of a new class of bifunctional oxidoreductase/Diels-Alderase, which was previously annotated as an NmrA-like transcriptional regulator. We demonstrate that CtdP catalyses the inherently disfavoured cycloaddition to form the bicyclo[2.2.2]diazaoctane scaffold with a strict α-anti-selectivity. Guided by computational studies, we reveal a NADP+/NADPH-dependent redox mechanism for the CtdP-catalysed inverse electron demand Diels-Alder cycloaddition, which serves as the first example of a bifunctional Diels-Alderase that utilizes this mechanism.

Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature. The pathophysiology of GBM is characterized by multifarious genetic abrasions that deactivate tumor suppressor genes, induce transforming genes, and over-secretion of pro-survival genes, resulting in oncogene sustainability. Synthetic lethality is a destructive process in which the episode of a single genetic consequence is tolerable for cell survival, while co-episodes of multiple genetic consequences lead to cell death. This targeted drug approach, centered on the genetic concept of synthetic lethality, is often selective for DNA repair-deficient GBM cells with restricted toxicity to normal tissues. DNA repair pathways are key modalities in the generation, treatment, and drug resistance of cancers, as DNA damage plays a dual role as a creator of oncogenic mutations and a facilitator of cytotoxic genomic instability. Although several research advances have been made in synthetic lethality modalities for GBM therapy, no review article has summarized these therapeutic modalities. Thus, this review focuses on the innovative advances in synthetic lethality modalities for GBM therapy.

Abstract Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.

Background: In recent years, computer-aided diagnosis for skin conditions has made significant strides, primarily driven by artificial intelligence (AI) solutions. However, despite this progress, the efficiency of AI-enabled systems remains hindered by the scarcity of high-quality and large-scale datasets, primarily due to privacy concerns. Methods: This research circumvents privacy issues associated with real-world acne datasets by creating a synthetic dataset of human faces with varying acne severity levels (mild, moderate, and severe) using Generative Adversarial Networks (GANs). Further, three object detection models—YOLOv5, YOLOv8, and Detectron2—are used to evaluate the efficacy of the augmented dataset for detecting acne. Results: Integrating StyleGAN with these models, the results demonstrate the mean average precision (mAP) scores: YOLOv5: 73.5%, YOLOv8: 73.6%, and Detectron2: 37.7%. These scores surpass the mAP achieved without GANs. Conclusions: This study underscores the effectiveness of GANs in generating synthetic facial acne images and emphasizes the importance of utilizing GANs and convolutional neural network (CNN) models for accurate acne detection.

Abstract Sclerotinia sclerotiorum is a widespread fungal pathogen responsible for significant crop losses across the globe. The challenge of breeding resistant varieties is exacerbated by the fungus's sophisticated pathogenic mechanisms. A pivotal factor in the host-pathogen interaction is the regulation of reactive oxygen species (ROS) within both the fungi and the host plants. However, there is currently no efficient strategy to leverage this interaction mechanism for developing disease-resistant crop varieties. Here, we introduce an engineered ROS scavenging system designated as syn-ROS for impairing ROS neutralization in S. sclerotiorum while concurrently fortifying it in the host. The syn-ROS system comprises gene silencing constructs targeting the S. sclerotiorum Cu/Zn superoxide dismutase (SsSOD) and its copper chaperone (SsCCS), alongside overexpression constructs for the Arabidopsis thaliana AtSOD1 and AtCCS. Transgenic plants carrying the syn-ROS system demonstrated a marked enhancement in resistance to S. sclerotiorum. Upon infection, the expression of SsSOD and SsCCS was reduced, while the expression of AtSOD1 and AtCCS was enhanced in syn-ROS transgenic plants. Moreover, the infected syn-ROS plants showed decreased Cu/Zn SOD enzyme activity and elevated ROS concentrations within the fungal cells. In contrast, the cells of A. thaliana manifested increased Cu/Zn SOD enzyme activity and lowered ROS levels. Collectively, these findings suggest a novel and promising approach for contriving plants with robust resistance by synthetically manipulating ROS scavenging activities in the interaction between the host and S. sclerotiorum.

Background: In recent years, computer-aided diagnosis for skin conditions has made significant strides, primarily driven by artificial intelligence (AI) solutions. However, despite this progress, the efficiency of AI-enabled systems remains hindered by the scarcity of high-quality and large-scale datasets, primarily due to privacy concerns. Methods: This research circumvents privacy issues associated with real-world acne datasets by creating a synthetic dataset of human faces with varying acne severity levels (mild, moderate, and severe) using Generative Adversarial Networks (GANs). Further, three object detection models—YOLOv5, YOLOv8, and Detectron2—are used to evaluate the efficacy of the augmented dataset for detecting acne. Results: Integrating StyleGAN with these models, the results demonstrate the mean average precision (mAP) scores: YOLOv5: 73.5%, YOLOv8: 73.6%, and Detectron2: 37.7%. These scores surpass the mAP achieved without GANs. Conclusions: This study underscores the effectiveness of GANs in generating synthetic facial acne images and emphasizes the importance of utilizing GANs and convolutional neural network (CNN) models for accurate acne detection. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii have emerged as major clinical threats owing to the increasing prevalence of ventilator-associated pneumonia caused by multidrug-resistant or extensively drug-resistant strains. The present study aimed to assess the antibacterial effects and efficacy of LL-37 fragment GF-17D3 and synthetic Scolopendin A2 peptides against resistant clinical strains in vitro and in vivo models. P. aeruginosa, S. aureus, and A. baumannii were isolated from clinical infections. Their antibiotic resistance and minimum inhibitory concentration were assessed. LL-37 fragment GF-17D3 peptide was selected from available databases. Scolopendin A2 peptide's 6th amino acid (proline) was substituted with lysine and peptides and MICs were determined. The biofilm inhibitory activity was quantified at sub MIC concentrations. Synergetic effects of Scolopendin A2 and imipenem were assessed by checkerboard. After mice nasal infection with P. aeruginosa, peptides LD50 was determined. Isolates harbored complete resistance toward the majority of antibiotics and MIC values ranged between 1 and > 512 µg/ml. The majority of isolates exhibited strong biofilm activity. Synthetic peptides showed lower MIC values than antibiotic agents and the lowest MIC values were obtained for synthetic peptides in combination with antibiotics. The Synergisms effect of Scolopendin A2 with imipenem was also determined. Scolopendin A2 was found to have antibacterial efficacy against P. aeruginosa, S. aureus, and A. baumannii with MIC 64 µg/ml, 8 µg/ml, and 16 µg/ml, respectively, and LL37 showed antibacterial efficacy against P. aeruginosa, S. aureus, and A. baumannii with MIC 128 µg/ml, 32 µg/ml, and 32 µg/ml, respectively. Both AMPs decreased biofilms by ≥ 96% at 1 × MIC. The biofilm inhibitory activity was measured at sub MIC concentrations of the peptides and the results demonstrated that Scolopendin A2 exhibited anti-biofilm activity at 1/4 × MIC and 1/2 × MIC concentrations was 47.9 to 63.8%, although LL37 among 1/4 × MIC and 1/2 × MIC concentrations was 21.3 to 49.6% against three pathogens. The combination of Scolopendin A2 and antibiotics demonstrated synergistic activity-resistant strains with FIC values ≤ 0.5 for three pathogens, while LL37 and antibiotics showed synergistic activity FIC values ≤ 0.5 for only P. aeruginosa. Infection model Scolopendin A2 with Imipenem (2 × MIC) was efficacious in vivo, with a 100% survival rate following treatment at 2 × MIC after 120 h. The mRNA expression of biofilm-related genes was decreased for both peptides. Synthesis Scolopendin A2 decreased the expression of biofilm formation genes compared to the control group. Synthetic Scolopendin A2 exhibits antimicrobial activity without causing toxicity on the human epithelial cell line. Based on our findings, it seems that synthetic Scolopendin A2 is an appropriate antimicrobial source. That could be a promising option in combination with antibiotics for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant bacteria. Nevertheless, additional experiments are required to assess another potential of this novel AMP. [ABSTRACT FROM AUTHOR]

Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected. [ABSTRACT FROM AUTHOR]

Interleukin‐6 (IL‐6)‐type cytokines not only have key immunomodulatory functions that affect the pathogenesis of diseases such as autoimmune diseases, chronic inflammatory conditions, and cancer, but also fulfill important homeostatic tasks. Even though the pro‐inflammatory arm has hindered the development of therapeutics based on natural‐like IL‐6‐type cytokines to date, current synthetic trends might pave the way to overcome these limitations and eventually lead to immune‐inert designer cytokines to aid type 2 diabetes and brain injuries. Those synthetic biology approaches include mutations, fusion proteins, and inter‐cytokine swapping, and resulted in IL‐6‐type cytokines with altered receptor affinities, extended target cell profiles, and targeting of non‐natural cytokine receptor complexes. Here, we survey synthetic cytokine developments within the IL‐6‐type cytokine family and discuss potential clinical applications. [ABSTRACT FROM AUTHOR]

Arteries and veins develop different types of occlusive diseases and respond differently to injury. The biological reasons for this discrepancy are not well understood, which is a limiting factor for the development of vein-targeted therapies. This study contrasts human peripheral arteries and veins at the single-cell level, with a focus on cell populations with remodeling potential. Upper arm arteries (brachial) and veins (basilic/cephalic) from 30 organ donors were compared using a combination of bulk and single-cell RNA sequencing, proteomics, flow cytometry, and histology. The cellular atlases of six arteries and veins demonstrated a 7.8× higher proportion of contractile smooth muscle cells (SMCs) in arteries and a trend toward more modulated SMCs. In contrast, veins showed a higher abundance of endothelial cells, pericytes, and macrophages, as well as an increasing trend in fibroblasts. Activated fibroblasts had similar proportions in both types of vessels but with significant differences in gene expression. Modulated SMCs and activated fibroblasts were characterized by the upregulation of MYH10, FN1, COL8A1, and ITGA10. Activated fibroblasts also expressed F2R, POSTN, and COMP and were confirmed by F2R/CD90 flow cytometry. Activated fibroblasts from veins were the top producers of collagens among all fibroblast populations from both types of vessels. Venous fibroblasts were also highly angiogenic, proinflammatory, and hyper-responders to reactive oxygen species. Differences in wall structure further explain the significant contribution of fibroblast populations to remodeling in veins. Fibroblasts are almost exclusively located outside the external elastic lamina in arteries, while widely distributed throughout the venous wall. In line with the above, ECM-targeted proteomics confirmed a higher abundance of fibrillar collagens in veins vs. more basement ECM components in arteries. The distinct cellular compositions and transcriptional programs of reparative populations in arteries and veins may explain differences in acute and chronic wall remodeling between vessels. This information may be relevant for the development of antistenotic therapies. [ABSTRACT FROM AUTHOR]

Background: The in vivo assessment of a novel compound is a pivotal step in the development of a new drug. In this study, we selected 1-(2-bromophenyl)-1,11-dihydro-3H-benzo[h]pyrano[3,2-c]quinoline-3,12(2H)-dione (2-BDBPQD), identified as an exemplary α-glucosidase inhibitor in preliminary in vitro assays, for further evaluation in an in vivo anti-diabetic context. Methods: The in vivo anti-diabetic effect of 2-BDBPQD was assessed using a streptozotocin (STZ)-induced diabetic Wistar rat model. Recognizing the relevance of lipid factors in diabetes, we also investigated the impact of this compound on the lipid profile of diabetic Wistar rats. In silico studies, encompassing docking studies and pharmacokinetic predictions of 2-BDBPQD, were conducted. Results: The results obtained indicated a significant reduction in blood glucose levels with 2-BDBPQD treatment compared to acarbose. However, no significant effects on the lipid profile were observed. In silico studies revealed that 2-BDBPQD interacted with key residues in the α-glucosidase active site and exhibited favorable pharmacokinetic properties. Conclusion: In summary, the study demonstrated the in vivo anti-hyperglycemic activity of 2-BDBPQD. Nevertheless, further in vivo evaluations are recommended to comprehensively assess its potential as a new drug for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Biometric fingerprint identification hinges on the reliability of its sensors; however, calibrating and standardizing these sensors poses significant challenges, particularly in regards to repeatability and data diversity. To tackle these issues, we propose methodologies for fabricating synthetic 3D fingerprint targets, or phantoms, that closely emulate real human fingerprints. These phantoms enable the precise evaluation and validation of fingerprint sensors under controlled and repeatable conditions. Our research employs laser engraving, 3D printing, and CNC machining techniques, utilizing different materials. We assess the phantoms' fidelity to synthetic fingerprint patterns, intra-class variability, and interoperability across different manufacturing methods. The findings demonstrate that a combination of laser engraving or CNC machining with silicone casting produces finger-like phantoms with high accuracy and consistency for rolled fingerprint recordings. For slap recordings, direct laser engraving of flat silicone targets excels, and in the contactless fingerprint sensor setting, 3D printing and silicone filling provide the most favorable attributes. Our work enables a comprehensive, method-independent comparison of various fabrication methodologies, offering a unique perspective on the strengths and weaknesses of each approach. This facilitates a broader understanding of fingerprint recognition system validation and performance assessment. [ABSTRACT FROM AUTHOR]

Objectives: In view of the problem that it is difficult to identify the high hidden landslides by traditional ground investigation methods, the author's team have proposed the space-air-ground investigation system of landslide detection and monitoring. It has been applied nationwide with good results. However, there are few academic reports about it. In the study area of Danba County, where landslide disasters are frequent. Therefore, the detection and monitoring of potential landslides based on the space-air-ground investigation system was carried out. Methods: First, stacking-interferometric synthetic aperture radar(StackingInSAR) and small baseline subsets-InSAR(SBAS-InSAR) were combined with high-resolution optical remote sensing to achieve a wide-area census of active landslides in the whole study area, and the results of Stacking-InSAR and SBAS-InSAR were compared and analyzed. Second, light detection and ranging (LiDAR) technology and unmanned aerial vehicle aerial photography technology were used to conduct a detailed investigation of landslides in high-risk areas around Danba County, and further verification of major landslides through on-site investigation. Finally, SBAS-InSAR technology was used to monitor and analyze the deformation of typical landslides. Results: 41 active landslides were detected in the study area by using the space-air-ground investigation system. They are mainly local resurgence of large ancient land-slide accumulations under long-term gravity, river scouring and human engineering activities, etc. Most of the landslide deformations have a good correlation with rainfall. Conclusions: In the process of identifying landslides by using the space-air-ground investigation system, it is necessary to give full play to the advantages of each technical means. [ABSTRACT FROM AUTHOR]

Breast-conserving surgery (BCS) is a well-established standard treatment option alternative to mastectomy for patients with early breast cancer that consists of a lumpectomy followed by adjuvant radiotherapy. However, irradiated tissues are at an increased risk of wound healing complications when post-treatment surgical management is required. The management of an irradiated wound dehiscence can be challenging, as it often requires a multimodal treatment approach that includes more invasive interventions when compared to a traditional surgical wound dehiscence. We present a 64 year old female patient with a remote history of right BCS with radiation therapy for early breast cancer 12 years ago, who recently required a simple mastectomy due to ipsilateral breast cancer recurrence. The post-operative course was complicated by dehiscence of the mastectomy wound. After standard wound care therapies failed, her surgical wound successfully healed after treatment with a synthetic electrospun fiber matrix application. Patients with additional comorbidities often do not qualify for invasive reconstructive options; therefore, effective local management options are warranted. This is the first reported case documenting synthetic electrospun fiber matrix efficacy and safety in healing a dehisced surgical wound within a previously irradiated fibrotic area, without the need for further invasive surgical intervention. Larger scale research, such as a prospective cohort study or randomized control trial, is needed to investigate its novel use in irradiated wounds. [ABSTRACT FROM AUTHOR]

Background: The anterior maxilla is challenging regarding aesthetic rehabilitation. Current bone augmentation techniques are complex and 3D-printed bioceramic bone grafts can simplify the intervention. Aim: A four-teeth defect in the anterior maxilla was reconstructed with a 3D-printed synthetic patient-specific bone graft in a staged approach for dental implant delivery. Methods: The bone graft was designed using Cone-Beam Computed Tomography (CBCT) images. The bone graft was immobilized with fixation screws. Bone augmentation was measured on CBCT images at 11 days and 8 and 13 months post-surgery. A biopsy sample was retrieved at reentry (10 months post-augmentation) and evaluated by histological and micro-computed tomography assessments. The definitive prosthesis was delivered 5 months post-reentry and the patient attended a visit 1-year post-loading. Results: A total bone width of 8 mm was achieved (3.7 mm horizontal bone gain). The reconstructed bone remained stable during the healing period and was sufficient for placing two dental implants (with an insertion torque > 35 N·cm). The fractions of new bone, bone graft, and soft tissue in the biopsy were 40.77%, 41.51%, and 17.72%, respectively. The histological assessment showed no signs of encapsulation, and mature bone was found in close contact with the graft, indicating adequate biocompatibility and suggesting osteoconductive properties of the graft. At 1-year post-loading, the soft tissues were healthy, and the dental implants were stable. Conclusions: The anterior maxilla's horizontal ridge can be reconstructed using a synthetic patient-specific 3D-printed bone graft in a staged approach for implant placement. The dental implants were stable and successful 1-year post-loading. [ABSTRACT FROM AUTHOR]

Brain segmentation from neonatal MRI images is a very challenging task due to large changes in the shape of cerebral structures and variations in signal intensities reflecting the gestational process. In this context, there is a clear need for segmentation techniques that are robust to variations in image contrast and to the spatial configuration of anatomical structures. In this work, we evaluate the potential of synthetic learning, a contrast‐independent model trained using synthetic images generated from the ground truth labels of very few subjects. We base our experiments on the dataset released by the developmental Human Connectome Project, for which high‐quality images are available for more than 700 babies aged between 26 and 45 weeks postconception. First, we confirm the impressive performance of a standard UNet trained on a few volumes, but also confirm that such models learn intensity‐related features specific to the training domain. We then confirm the robustness of the synthetic learning approach to variations in image contrast. However, we observe a clear influence of the age of the baby on the predictions. We improve the performance of this model by enriching the synthetic training set with realistic motion artifacts and over‐segmentation of the white matter. Based on extensive visual assessment, we argue that the better performance of the model trained on real T2w data may be due to systematic errors in the ground truth. We propose an original experiment allowing us to show that learning from real data will reproduce any systematic bias affecting the training set, while synthetic models can avoid this limitation. Overall, our experiments confirm that synthetic learning is an effective solution for segmenting neonatal brain MRI. Our adapted synthetic learning approach combines key features that will be instrumental for large multisite studies and clinical applications. [ABSTRACT FROM AUTHOR]

Natural and synthetic polymers are a versatile platform for developing biomaterials in the biomedical and environmental fields. Natural polymers are organic compounds that are found in nature. The most common natural polymers include polysaccharides, such as alginate, hyaluronic acid, and starch, proteins, e.g., collagen, silk, and fibrin, and bacterial polyesters. Natural polymers have already been applied in numerous sectors, such as carriers for drug delivery, tissue engineering, stem cell morphogenesis, wound healing, regenerative medicine, food packaging, etc. Various synthetic polymers, including poly(lactic acid), poly(acrylic acid), poly(vinyl alcohol), polyethylene glycol, etc., are biocompatible and biodegradable; therefore, they are studied and applied in controlled drug release systems, nano-carriers, tissue engineering, dispersion of bacterial biofilms, gene delivery systems, bio-ink in 3D-printing, textiles in medicine, agriculture, heavy metals removal, and food packaging. In the following review, recent advancements in polymer chemistry, which enable the imparting of specific biomedical functions of polymers, will be discussed in detail, including antiviral, anticancer, and antimicrobial activities. This work contains the authors' experimental contributions to biomedical and environmental polymer applications. This review is a vast overview of natural and synthetic polymers used in biomedical and environmental fields, polymer synthesis, and isolation methods, critically assessessing their advantages, limitations, and prospects. [ABSTRACT FROM AUTHOR]

Sclerotinia sclerotiorum is a widespread fungal pathogen responsible for significant crop losses across the globe. The challenge of breeding resistant varieties is exacerbated by the fungus's sophisticated pathogenic mechanisms. A pivotal factor in the host-pathogen interaction is the regulation of reactive oxygen species (ROS) within both the fungi and the host plants. However, there is currently no efficient strategy to leverage this interaction mechanism for developing disease-resistant crop varieties. Here, we introduce an engineered ROS scavenging system designated as syn-ROS for impairing ROS neutralization in S. sclerotiorum while concurrently fortifying it in the host. The syn-ROS system comprises gene silencing constructs targeting the S. sclerotiorum Cu/Zn superoxide dismutase (SsSOD) and its copper chaperone (SsCCS), alongside overexpression constructs for the Arabidopsis thaliana AtSOD1 and AtCCS. Transgenic plants carrying the syn-ROS system demonstrated a marked enhancement in resistance to S. sclerotiorum. Upon infection, the expression of SsSOD and SsCCS was reduced, while the expression of AtSOD1 and AtCCS was enhanced in syn-ROS transgenic plants. Moreover, the infected syn-ROS plants showed decreased Cu/Zn SOD enzyme activity and elevated ROS concentrations within the fungal cells. In contrast, the cells of A. thaliana manifested increased Cu/Zn SOD enzyme activity and lowered ROS levels. Collectively, these findings suggest a novel and promising approach for contriving plants with robust resistance by synthetically manipulating ROS scavenging activities in the interaction between the host and S. sclerotiorum. [ABSTRACT FROM AUTHOR]

This article investigates the forms and functions of adjectival intensification in West Germanic. With corpus data from different discourse types, we challenge claims that German tends to use synthetic means and Dutch is between German and English but more like English in its preference for analytic ones. Our results show that all three languages, and Afrikaans too, favor analytic intensifiers but also that only English employs synthetic ones to a lesser extent. The other languages are found to use synthetic forms more especially in literature. The study also offers corpus-based support for an earlier hypothesis that both English and German prefer amplifying to downtoning adjectives. We show that this tendency exists more pronouncedly in Afrikaans and Dutch too and that English speech stands out with more functionally ambiguous intensifiers. The article also explores possible explanations for its findings in (dis)similarities in word formation, discourse types' linguistic potential and politeness [ABSTRACT FROM AUTHOR]

A vital trial in gene delivery implicates the want for competent and safe delivery systems to announce therapeutic genes into target cells. Virus vectors are disparaged for genetic toxicity, immune response, and poor delivery ability for large-sized genetic materials. Polyplexes having cationic biodegradable polymeric materials (BPMs) can substitute viral vectors. Synthetic BPMs-based non-viral gene delivery systems can be embedded with assorted characteristics like biocompatibility and self-assembly. Using nanoscale BPMs, delicate manipulation of a broad scope of physicochemical properties, like surface charge, stimuli-sensitivity, and particle size can be executed. This contribution summarizes the recent developments of BPMs in gene delivery systems. [ABSTRACT FROM AUTHOR]

The Star Trek franchise's depiction of artificial intelligence (AI) and affiliated technologies—namely, supercomputers, androids, and holograms—evokes common themes and motifs from the myths of the ancient Mediterranean. This article analyzes the mythological underpinnings of Star Trek's historical treatment and approach to AI, from The Original Series to The Next Generation and up through the newest additions to the canon, Short Treks, and Picard. AI in Star Trek, like Data, the Doctor, and Zora, expresses qualities associated with divinity: superhuman strength, intelligence, and agelessness. These very qualities distinguish them from humans and bar them from considerations of personhood. Like the Greek gods of myth, AI can present as immortal, which fundamentally distinguishes it from mortal humans, as seen in the tensions between gods and humans in Homer's Odyssey and the Homeric Hymns. The ancient tension between mortal and immortal is manifested in the combative relationship between organic creator and artificial creation, a common sci-fi trope, that can lead to a cycle of fear and hostility evocative of the divine generational warfare in Hesiod's Theogony. The artificial–organic tension resonates with the contemporary audience's conflicted experiences with evolving technologies and problematizes the show's presentation of the evolution of humanity into a posthuman existence. Just as mythology is used to consider humanity relative to the divine, narratives about AI are fertile ground to analyze what it means to be human and establish parameters for what is decidedly not human. [ABSTRACT FROM AUTHOR]

Due to the ability to perform the parallel measurement of multiple single chains and exert precise control over stretching force in the sub‐nanonewton regime, magnetic tweezers (MT) are a suitable tool to study the individual chain conformations and inherent behaviors of polymers. Herein, we examined the applications of MT in studying single synthetic polymers, distinct from previous reviews focusing on biological polymers such as DNAs. We first presented an overview of the technical aspects of MT, including the imaging setup, the algorithm of three‐dimensional single particle tracking, the configuration of magnets, the calibration and control of magnetic forces, the assembly of flow cells, and the polymer tethering methods. Then, we discussed selected examples highlighting the utilization of MT in studying the chain conformation, mechanical properties, ion and ligands effect, regime transition mechanism, and polymerization dynamics of single synthetic polymers. We envision that MT can serve as a powerful toolbox for delving into the structure–property correlations at the single chain level, which provides quantitative validations for building the theoretical models of synthetic polymers. In the end, we contemplated potential avenues and opportunities for future research in this domain. [ABSTRACT FROM AUTHOR]

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Mesh is a synthetic material used to treat stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in women. There have been several reports by patients of complications around the world and some countries have suspended the use of vaginally inserted mesh for the treatment of SUI and POP due to complications. The aim of this document is to address the types of mesh procedures performed and provide terminology for mesh removal which can be easily understood by health-care providers and patients/consumers, avoiding miscommunication which has been highlighted in the Cumberlege report in the United Kingdom.

Deep learning has unequivocally emerged as the backbone of simple to highly sensitive systems demanding artificial intelligence across diverse domains. For instance, foundation models based on deep neural networks (DNNs) can play a crucial role in the design of security-sensitive systems, such as facial recognition systems (FRS). Despite achieving exceptional accuracy and human-like performance, DNNs tend to be severely sensitive to adversarial attacks. While DNNs are deemed irreplaceable in the artificial intelligence domain, the vulnerability of DNNs against adversarial examples can be detrimental to sensitive systems robustness. The paper presents a pilot study introducing an attack-defense framework aimed at enhancing the robustness of FRS against evasion attacks. Our generative adversarial network (GAN) based attack successfully deceives FRS, demonstrating that they are not only vulnerable against synthetic images visibly comparable to real user images (i.e., best-match scenarios) but also to partially constructed user images (i.e., average-match scenarios). Based on our analysis, we propose a novel solution that extends the visual prompt engineering (VPE) concept for detecting synthetic images to secure downstream tasks in FRS. The VPE detection module achieves an accuracy of 97.92% in the average-match scenario and 87.08% in the best-match scenario on our generated dataset. Furthermore, we use the Trueface postsocial dataset to validate the efficacy of the detection module obtaining an accuracy of 91.96%. Our experimental evaluation shows that VPE can effectively tackle the GAN attacks from average-match to best-match scenarios, thus enhancing the overall robustness of a security-sensitive system against evasion attacks.