Search Results (5,153)

This study aimed to improve the mechanical properties and microstructure of recycled aggregate concrete (RAC) by incorporating carbon fibers (CFs) and nano-SiO₂ (NS) to promote the optimal utilization of RAC. The mechanical properties of the RAC were enhanced by both single and hybrid additions of CFs and NS, and the hybrid addition had a better strengthening effect. From the experimental results, it was found that the addition of CFs could increase the 28 d compressive strength and splitting strength of the RAC by 9.05% and 22.36%, respectively. The hybrid CFs and NS were more conducive to improving the mechanical properties of the RAC, and the enhancement effect increased first and then decreased with an increase in the NS content. The optimal content of NS was 0.8 wt%, which increased the 28 d compressive strength and splitting strength of the RAC by 20.51% and 14.53%, respectively. The microstructure results indicated that the addition of CFs had little effect on the optimized pore structure of the RAC, but the crack inhibition action of the CFs could improve the mechanical properties of the RAC. The addition of NS reduced the content of CH and facilitated the formation of more (C–S–H) gel. The hydrated calcium silicate (C–S–H) gel significantly decreased the porosity and transformed harmful capillary pores and harmful pores into harmless capillary pores and gel pores, thus improving the mechanical properties of the RAC. Therefore, the use of hybrid CFs and NS was more conducive to enhancing the performance of RAC for building materials. Full article

Harnessing the body’s intrinsic resources for wound healing is becoming a rapidly advancing field in regenerative medicine research. This study investigates the effects of the topical application of a novel porcine Hypoxia Preconditioned Serum Hydrogel (HPS-H) on wound healing using a minipig model over a 21-day period. Porcine HPS exhibited up to 2.8× elevated levels of key angiogenic growth factors (VEGF-A, PDGF-BB, and bFGF) and demonstrated a superior angiogenic effect in a tube formation assay with human umbilical endothelial cells (HUVECs) in comparison to porcine normal serum (NS). Incorporating HPS into a hydrogel carrier matrix (HPS-H) facilitated the sustained release of growth factors for up to 5 days. In the in vivo experiment, wounds treated with HPS-H were compared to those treated with normal serum hydrogel (NS-H), hydrogel only (H), and no treatment (NT). At day 10 post-wounding, the HPS-H group was observed to promote up to 1.7× faster wound closure as a result of accelerated epithelialization and wound contraction. Hyperspectral imaging revealed up to 12.9% higher superficial tissue oxygenation and deep perfusion in HPS-H-treated wounds at day 10. The immunohistochemical staining of wound biopsies detected increased formation of blood vessels (CD31), lymphatic vessels (LYVE-1), and myofibroblasts (alpha-SMA) in the HPS-H group. These findings suggest that the topical application of HPS-H can significantly accelerate dermal wound healing in an autologous porcine model. Full article

Background: Artemisia annua, a plant with antiviral potential, has shown promise against various viral infections, yet its mechanisms of action are not fully understood. This study explores A. annua’s antiviral effects using network pharmacology and molecular docking, focusing on key active compounds and their interactions with viral protein targets, particularly within the JAK-STAT signaling pathway—a critical mediator of immune responses to viral infections. Methods: From the TCMSP database, we identified eight active compounds and 335 drug targets for A. annua, with 19 intersecting targets between A. annua compounds and viral proteins. A protein–protein interaction (PPI) network highlighted 10 key hub genes, analyzed further through Gene Ontology (GO) and KEGG pathways to understand their immune and antiviral roles. ADMET properties of the active compound Patuletin (MOL004112) were assessed, followed by 200 ns molecular dynamics simulations to examine its stability in complex with JAK2. Results: PPI analysis identified JAK2, MAPK3, MAPK1, JAK1, PTPN1, HSPA8, TYK2, RAF1, MAPT, and HMOX1 as key hub genes, with JAK2 emerging as a critical regulator of immune and antiviral pathways. ADMET analysis confirmed Patuletin’s favorable pharmacokinetic properties, and molecular dynamics simulations showed a stable Patuletin-JAK2 complex, with FEL analysis indicating minimal disruption to JAK2’s intrinsic flexibility. Conclusions: These findings highlight JAK2 as a promising target in the antiviral activity of A. annua compounds, particularly Patuletin, supporting its potential as an antiviral agent and providing a foundation for further research on A. annua’s therapeutic applications. Full article

Climate change has significant implications for agriculture, especially in viticulture, where temperature plays a crucial role in grapevine (Vitis vinifera) growth. Mendoza’s climate is ideal for producing high-quality wines, but 21st-century climate change is expected to have negative impacts. This study aimed to evaluate the effects of increased temperature on the phenology, physiology, and yield of Malbec, Bonarda, and Syrah. A field trial was conducted over two seasons (2019–2020 and 2020–2021) in an experimental vineyard with an active canopy heating system (+2–4 °C). Phenological stages (budburst, flowering, fruit set, veraison, harvest), shoot growth (SG), number of shoots (NS), stomatal conductance (gs), chlorophyll content (CC), chlorophyll fluorescence (CF), and water potential (ψa) were measured. Additionally, temperature, relative humidity, light intensity, and canopy temperature were recorded. Heat treatment advanced all phenological stages by approximately two weeks, increased SG and NS, and reduced gs and ψa during the hottest months. CC and CF remained unaffected. The treatment also resulted in lower yields, reduced acidity, and increased °Brix in both seasons. Overall, rising temperatures due to climate change advance the phenological phases of Malbec, Syrah, and Bonarda, leading to lower yields, higher °Brix, and lower acidity, although physiological variables remained largely unchanged. Full article

Background: Histone deacetylase 6 (HDAC6) plays a crucial role in neurological, inflammatory, and other diseases; thus, it has emerged as an important target for therapeutic intervention. To date, there are no FDA-approved HDAC6-targeting drugs, and most pipeline candidates suffer from poor target engagement, inadequate brain penetration, and low tolerability. There are a few HDAC6 clinical candidates for the treatment of mostly non-CNS cancers as their pharmacokinetic liabilities exclude them from targeting HDAC6-implicated neurological diseases, urging development to address these challenges. They also demonstrate off-target toxicity due to limited selectivity, leading to adverse effects in patients. Selective inhibitors have thus been the focus of development over the past decade, though no selective and potent HDAC6 inhibitor has yet been approved. Methods: This study involved an integrated virtual screening against HDAC6 using the DrugBank database to identify repurposed drugs capable of inhibiting HDAC6 activity. The primary assessment involved the determination of the ability of molecules to bind with HDAC6. Subsequently, interaction analyses and 500 ns molecular dynamics (MD) simulations followed by essential dynamics were carried out to study the conformational flexibility and stability of HDAC6 in the presence of the screened molecules, i.e., penfluridol and pimozide. Results: The virtual screening results pinpointed penfluridol and pimozide as potential repurposed drugs against HDAC6 based on their binding efficiency and appropriate drug profiles. The docking results indicate that penfluridol and pimozide share the same binding site as the reference inhibitor with HDAC6. The MD simulation results showed that stable protein–ligand complexes of penfluridol and pimozide with HDAC6 were formed. Additionally, MMPBSA analysis revealed favorable binding free energies for all HDAC6–ligand complexes, confirming the stability of their interactions. Conclusions: The study implies that both penfluridol and pimozide have strong and favorable binding with HDAC6, which supports the idea of repositioning these drugs for the management of neurodegenerative disorders. However, further in-depth studies are needed to explore their efficacy and safety in biological systems. Full article

In this paper, a high-repetition-rate, high-peak-power burst-mode nanosecond 355 nm UV laser was demonstrated. A quasi-continuous wave (QCW) laser diode (LD) side-pumped electro-optical (EO) Q-switched burst-mode Nd: YAG laser was performed as the fundamental laser source. Under the pumping duration of 250 μs and a burst repetition rate of 100 Hz, the pulse energy of 20 kHz burst-mode UV laser reached 5.3 mJ with a single pulse energy of 1.325 mJ, pulse width of 68 ns, resulting in a peak power of 19.49 kW. The as-generated millijoule burst-mode UV laser has great potential for high-end processing of laser lift-off, annealing and slicing in display semiconductor fields. Full article

The detection of heavy metal ions and organic pollutants from water sources remains critical challenges due to their detrimental effects on human health and the environment. Herein, a nitrogen and sulfur co-doped carbon quantum dot (NS-CQDs) fluorescent sensor was developed using a microwave-assisted carbonization method for the detection of Fe³⁺ ions and hydroquinone (HQ) in aqueous solutions. NS-CQDs exhibit excellent optical properties, enabling sensitive detection of Fe³⁺ and HQ, with detection limits as low as 3.40 and 0.96 μM. Notably, with the alternating introduction of Fe³⁺ and HQ, NS-CQDs exhibit significant fluorescence (FL) quenching and recovery properties. Based on this property, a reliable “on-off-on” detection mechanism was established, enabling continuous and reversible detection of Fe³⁺ and HQ. Furthermore, the low cytotoxicity of NS-CQDs was confirmed through successful imaging of HeLa cells, indicating their potential for real-time intracellular detection of Fe³⁺ and HQ. This work not only provides a green and rapid synthesis strategy for CQDs but also highlights their versatility as fluorescent probes for environmental monitoring and bioimaging applications. Full article

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF) represents a frequent form of PH related to left ventricular dysfunction. The pathophysiology of PH-HFpEF is intricate, and varied and includes vascular, cardiac, and pulmonary factors that contribute synergistically to developing this clinical syndrome. Improved knowledge of the pathophysiology of PH-HFpEF has paved the way for the use of new drugs such as angiotensin receptor neprilysin inhibitors (ARNIs), non-steroidal mineral corticoid receptor antagonist (nsMRA), sodium-glucose cotransporter inhibitors (SGLT2is), levosimendan, and glucagon-like peptide 1 (GLP-1) agonists. ARNIs are a widely used drug for the treatment of PH associated with heart failure with reduced ejection fraction. They have also recently been used in PH-HFpEF patients with hemodynamic benefits that need to be confirmed in future research. Finerenone is an innovative non-steroidal mineralocorticoid receptor antagonist that exhibits notable cardioprotective and renoprotective properties in individuals suffering from chronic diabetic kidney disease. It also enhances outcomes for patients with heart failure, whether they have mildly reduced or preserved ejection fraction. Moreover, in experimental studies, finerenone has been found to lower pulmonary artery pressure, reduce muscularization, and decrease the wall thickness of pulmonary arteries. SGLT2i have revolutionized the treatment of patients with heart failure irrespective of left ventricular ejection fraction, and their treatment is also associated with an improvement in the hemodynamics profile in patients with PH-HFpEF. Levosimendan is a widely used inodilator in the treatment of acute and advanced heart failure. In addition, its use in patients with PH-HFpEF (supported by the positive effects on pulmonary hemodynamics that levosimendan exerts) has recently demonstrated hemodynamic benefit in a small phase 2 study that paved the way for phase 3 studies and the creation of an oral formulation of levosimendan. Finally, GLP1 agonists are a class of drugs that, in preliminary evidence, have shown a positive effect on cardiac hemodynamics, mainly by facilitating left ventricular unloading. These effects, along with the reduction in insulin resistance and weight loss, likely lead to beneficial outcomes for PH-HFpEF patients, especially those with obesity as a comorbidity. Full article

Owing to their remarkable characteristics, two-dimensional (2D) layered, MAX phase materials have garnered significant attention in the field of optoelectronics in recent years. Herein, a novel MAX phase ceramic material (Mo₂TiAlC₂) was prepared into a saturable absorber (SA) by the spin-coating method for passively Q-switching (PQS), and its nonlinear optical absorption properties were characterized with a Tm:YAlO₃ (Tm:YAP) nanosecond laser. The structure characteristics and composition analysis revealed that the Mo₂TiAlC₂ material exhibits a well-defined and stable structure, with a uniform thin film successfully obtained through spin coating. In this study of a PQS laser by employing a Mo₂TiAlC₂-based SA, an average output power of 292 mW was achieved when the absorbed pump power was approximately 4.59 W, corresponding to a central output wavelength of 1931.2 nm. Meanwhile, a stable pulse with a duration down to 242.9 ns was observed at a repetition frequency of 47.07 kHz, which is the narrowest pulse width recorded among PQS solid-state lasers using MAX phase materials as SAs. Our findings indicate that the Mo₂TiAlC₂ MAX phase ceramic material is an excellent modulator and has promising potential for ultrafast nonlinear photonic applications. Full article

Thymoquinone (TQ), a bioactive compound from black cumin (Nigella sativa), has demonstrated a broad range of therapeutic effects. The aim of this study is to evaluate the antifungal efficacy of TQ by targeting key virulence factors in Candida albicans, specifically focusing on isocitrate lyase (ICL) activity, biofilm formation, and gene expression. This study explored TQ’s impact on ICL, a decisive enzyme in the glyoxylate cycle, along with its effect on hyphal formation, biofilm development, and the virulent gene expression of C. albicans through in silico and in vitro studies. Molecular docking revealed a binding energy of −6.4 kcal/mol between TQ and ICL, indicating moderate affinity. The stability of the ICL-TQ complex was validated through 50 ns molecular dynamics simulations, showing the root mean square deviation (RMSD) values of 0.35 nm for ICL and 0.38 nm for the complex. In vitro studies further validated these findings, showing a dose-dependent inhibition of ICL activity. TQ at 2 µg/mL reduced enzyme activity by 57%, and at 4 µg/mL, by 91.4%. Additionally, TQ disrupted the yeast-to-hyphae switch, a key virulence factor, with 1 and 2 µg/mL doses significantly inhibiting hyphal formation. The biofilm formation was similarly affected, with a 58% reduction at 2 µg/mL and an 83% reduction at 4 µg/mL. TQ also downregulated the ALS1 and HWP1 genes that are associated with adhesion and biofilm development, demonstrating its broad-spectrum antifungal activity. These findings suggest that TQ is a promising candidate for antifungal therapies, targeting multiple virulence factors in C. albicans and potentially overcoming biofilm-associated drug resistance. Future research should focus on in vivo validation, optimization for clinical applications, and expanding its spectrum against other drug-resistant fungal species. Full article

Geopolymer concrete is more low-carbon and environmentally friendly than Portland cement concrete. Nanoparticle modification can help to improve the mechanical and durability performance of concrete, but due to its large specific surface area and high activity, it may deteriorate its workability. However, there is currently limited research on the effect of nanomodification on the workability of freshly mixed self-compacting geopolymer concrete (SCGC). This article conducted SCGC workability experiments using the response surface methodology, which included 29 different mixtures. The effects of nano-silica (NS), nano-calcium carbonate (NC), alkali content (N/B), and water cement ratio (W/B) on the workability of SCGC were studied. The experimental results show that the addition of NS and NC can reduce the slump expansion of SCGC, and the combination of the two significantly increases the amplitude of slump expansion with the change in nanomaterial content. An increase in N/B will reduce the expansion time and clearance value of SCGC. As N/B increases from 4% to 4.4%, the slump extension of SCGC decreases, and with a further increase in N/B, the slump extension increases significantly to 68.1 cm, which means that the slump extension of SCGC increases by 9.5% as N/B increases from 4.4 to 5. This study can provide a reference for optimizing the fresh performance of geopolymer concrete and improving the mechanism of nanomaterial-modified geopolymer concrete. Full article

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. Methods: We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. Results: The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in PTPN11 were most commonly associated with pulmonary valve stenosis (PVS), while RAF1 mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development (p = 0.755), even though the likelihood ratio showed significance in that regard (p = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. Conclusions: The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype–phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies. Full article

A student’s choice of major is influenced by their parents and peers, as well as by the quality of the college department that offers the major and by broader cultural and economic issues. The student’s own personality, including their ability to reason about themselves and their interests, also contributes to the choice and its outcomes. In a preliminary study, we developed a Choice of Major Scale that depicts key aspects of students’ consideration of their major. Then, across three studies (Ns = 304, 466, and 492), we examined the students’ personal intelligence, defined as their capacity to reason about their own and other people’s personalities, as well as a Choice of Major Scale, and the relation of those variables to important academic outcomes. The results depicted a pattern that the students who better understood personality and were more engaged in choosing a major, compared to others, considered more majors initially, chose a major more quickly, and exhibited better academic outcomes subsequently. Full article

This study addresses a critical issue in plant taxonomy and phylogeny: the relationship between archaeological materials and potentially analogous living populations. Given the current limitations in definitively establishing the identity between archaeological and contemporary materials, we propose an intermediate approach. This approach serves as a useful framework while scientific methods advance towards definitively assessing whether an archaeological wheat sample, approximately 5000 years old from Central Europe, belongs to the same species as a modern wheat currently endemic to Central Asia. This approach consolidates the taxonomic validity of both archaeological and living materials, allowing them to be treated as distinct taxa while preserving the possibility of future identification convergence. Triticum vulgare var. antiquorum, an archaeobotanical small-grained, free-threshing wheat, was originally described in 1865. The 1982 discovery of morphologically similar living wheat in Tajikistan raised questions about their taxonomic relationship. Our study reviews the nomenclature of both taxa, designating an illustration from the original description of T. vulgare var. antiquorum as the lectotype to align with the traditional concept of the name. We address the ambiguity surrounding “Triticum antiquorum” as used by Russian agronomists and botanists, proposing a more precise circumscription within the current systematic framework of the genus based on cytogenetic data. Consequently, we describe a new taxon, Triticum sphaerococcum subsp. antiquorum. The holotype, selected from material with available cytogenetic data and grown from Professor Udachin’s original Pamir (Tajikistan) collection, is preserved in the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (WIR) collection. It is deposited at the I.M. Krasnoborov Herbarium of Central Siberian Botanical Garden SB RAS (NS), with an isotype at the WIR. This taxonomic revision and new subspecies designation provide a robust framework for reconciling archaeological and contemporary wheat diversity, advancing our understanding of wheat evolution and agricultural history. Full article

Adeno-Associated Viruses (AAVs, genus Dependoparvovirus) are the leading gene therapy vector. Until recently, efforts to enhance their capacity for gene delivery had focused on their capsids. However, efforts are increasingly shifting towards improving the viral replication protein, Rep78. We discovered that Rep78 and its shorter isoform Rep52 contain a strictly C-terminal sequence motif, DDx3EQ, conserved in most dependoparvoviruses. The motif is highly negatively charged and devoid of prolines. Its wide conservation suggests that it is required for the life cycle of dependoparvoviruses. Despite its short length, the motif’s strictly C-terminal position has the potential to endow it with a high recognition specificity. A candidate target of the DDx3EQ motif might be the DNA-binding interface of the origin-binding domain of Rep78, which is highly positively charged. Published studies suggest that this motif is not required for recombinant AAV production, but that substitutions within it might improve production. Full article