Search Results (2,775)

This study presents the development of a degradable and biocompatible calcium phosphate cement (CPC) co-loaded with gentamicin (1.25 wt%) and vancomycin (4.25 wt%) for the local treatment of polymicrobial bone infections. The antibiotics were incorporated —individually or in combination—into the solid phase of Graftys ^®Quickset (GQS), an injectable CPC. Antibiotic loading modifies some of the intrinsic properties of the GQS cement. Porosity exceeded 53%, compressive strength reduced around 5 MPa, which is comparable to calcium sulphates cements, and the setting time, although extended, remained within the clinically acceptable threshold (<20 min), ensuring suitable handling. A burst release of both antibiotics was observed within the first 24 h, with sustained release over time and no cytotoxic effects on human osteoblasts. The dual-loaded cement exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative strains, including methicillin-resistant isolates, in both planktonic and biofilm forms. Notably, the combination of both antibiotics demonstrated superior efficacy compared to either antibiotic alone. These findings suggest that this dual-antibiotic-loaded CPC offers a promising strategy for localised treatment of complex bone infections such as osteomyelitis, where polymicrobial involvement and antibiotic resistance pose significant therapeutic challenges. Full article

Background/Objectives: Resistance of pathogenic microorganisms to antibiotics poses a serious threat to public health and often leads to devastating consequences. In this context, one of the pressing challenges in pharmacochemistry is the search for new, effective antibiotics to combat severe human diseases. Cyclic lipopeptides have emerged as some of the most promising candidates and have been widely studied. These compounds are a class of microbial secondary metabolites produced by various microorganisms, and they possess significant medical and biotechnological importance. The defining structural feature of these compounds is the presence of both a hydrophobic fragment, primarily a hydrocarbon tail of varying length, and a hydrophilic cyclic peptide moiety. This hydrocarbon tail confers amphiphilic properties to the lipopeptides, which are essential for their broad spectrum of biological activities. Their mechanism of action involves disruption of the cell membrane, and in many cases, the formation of ion-permeable defects has also been shown. Results: This review summarizes the data on cyclic lipopeptides produced by Pseudomonas spp., Streptomyces spp., and Bacillus spp. that modify membrane permeability through the formation of ion channels. The main emphasis is on understanding how the structure of the CLP can be related to the probability and mode of pore formation. Conclusions: The findings can contribute to expanding the arsenal of effective antimicrobial agents with a mechanism of action that reduces the risk of developing resistance. Full article

Background/Objectives: The rise in antibiotic resistance presents a serious and urgent global health challenge, emphasizing the need to develop new therapeutic compounds. This study focuses on the design and evaluation of a novel series of hybrid molecules that combine the 2-quinolone and 1,2,3-triazole pharmacophores, both recognized for their broad-spectrum antimicrobial properties. Methods: A library of 29 candidate molecules was first designed using in silico techniques, including QSAR modeling, ADMET prediction, molecular docking, and molecular dynamics simulations, to optimize antibacterial activity and drug-like properties. The most promising compounds were then synthesized and characterized by ¹H and ¹³C NMR APT, mass spectrometry (MS), Fourier-transform infrared (FT-IR) spectroscopy, and UV-Vis spectroscopy. Results: Antibacterial evaluation revealed potent activity against both Gram-positive and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values ranging from 0.019 to 1.25 mg/mL. Conclusions: These findings demonstrate the strong potential of 2-quinolone–triazole hybrids as effective antibacterial agents and provide a solid foundation for the development of next-generation antibiotics to combat the growing threat of bacterial resistance. Full article

Antimicrobial peptides (AMPs) are small-molecule polypeptides with broad-spectrum antibacterial and immunomodulatory properties. As feed additives, they have demonstrated synergistic effects in aquaculture by enhancing growth performance and maintaining host health. Its negligible drug resistance makes it an ideal additive to replace antibiotics in the “antibiotic-free breeding” system. Antimicrobial peptides were added to the basic diet of the crucian carp (Carassius auratus) to assess their impacts on growth, muscle quality, antioxidant capacity, immune function, and key gene expression in the TLR4/NF-κB signaling pathway. Crucian carp were fed with experimental diets containing antimicrobial peptides for 49 days, namely four treatments: L0 (0 g/kg), L1 (0.2 g/kg), L2 (0.4 g/kg), and L3 (0.6 g/kg), with three repetitions of each treatment. The findings indicated that AMPs had the potential to improve growth performance and muscle quality. The final weight, WGR, and SGR of crucian carp of group L1 significantly increased compared with groups L0 and L3 (p < 0.05). The condition factor of group L2 significantly increased compared with group L0(p < 0.05). The FCR of groups L0, L1, and L2 was significantly reduced compared with group L3 (p < 0.05). The muscle redness of group L1 was significantly higher compared with groups L0, L2, and L3 (p < 0.05). The muscle shear force of groups L0, L1, and L2 was significantly lower compared with group L3 (p < 0.05). The crude protein content of groups L0, L1, and L2 showed significantly higher crude protein content than group L3 (p < 0.05). Conversely, the crude fat content was significantly lower in groups L1, L2, and L3 compared with group L0 (p < 0.05). The superoxide dismutase (SOD) activity of group L1 was significantly higher compared with groups L0, L2, and L3 (p < 0.05). The catalase (CAT) activity of groups L0 and L1 was significantly increased compared with groups L2 and L3 (p < 0.05). The malondialdehyde (MDA) content of groups L1 and L2 was significantly reduced compared with groups L0 and L3 (p < 0.05). The acid phosphatase (ACP) activity of groups L1 and L2 was significantly increased compared with group L0 (p < 0.05). The alkaline phosphatase (AKP) activity of group L1 was significantly increased compared with groups L0 and L3 (p < 0.05). Compared with groups L2 and L3, the lysozyme activity of group L1 was significantly increased (p < 0.05). The C3 content of groups L1, L2, and L3 was significantly higher compared with group L0 (p < 0.05). Similarly, C4 levels of groups L2 and L3 significantly exceeded group L0 (p < 0.05). For inflammatory cytokines, the IL-1 levels of groups L1 and L2 were significantly higher than those of group L0 (p < 0.05). The IL-6 and IL-12 levels of groups L0, L1, and L2 significantly increased compared with group L3 (p < 0.05). Compared with group L0, the levels of TNF and IFN-γ of groups L1, L2, and L3 were significantly higher (p < 0.05). Compared with group L0, the relative expression levels and protein expression levels of key genes TLR4, MyD88, IRAK4, TRAF6, and NF-κB of groups L1, L2, and L3 were significantly upregulated (p < 0.05). In conclusion, supplementation with 0.2–0.4 g/kg antimicrobial peptides promoted the growth of crucian carp, improved muscle quality, enhanced the antioxidant capacity, and boosted immunity through modulation of the TLR4/NF-κB signaling pathway. Full article

Geopolymers represent an innovative and environmentally sustainable alternative to traditional construction materials, offering significant potential for reducing anthropogenic CO₂ emissions. Among these, phosphoric acid-activated metakaolin-based systems have attracted increasing attention for their chemical and thermal resilience. In this study, we present a comprehensive structural and mechanical evaluation of metakaolin-based geopolymers synthesized across a wide range of Al/P molar ratios (0.8–4.0). Six formulations were systematically prepared and analyzed using X-ray powder diffraction (XRPD), small-angle X-ray scattering (SAXS), Fourier-transform infrared spectroscopy (FTIR), solid-state nuclear magnetic resonance (ssNMR), and complementary mechanical testing. The novelty of this work lies in the integrated mapping of composition–structure–property relationships across the broad Al/P spectrum under controlled synthesis, combined with the rare application of SAXS to reveal composition-dependent nanoscale domains (~18–50 nm). We identify a stoichiometric window at Al/P ≈ 1.5, where complete acid consumption leads to a structurally homogeneous AlVI–O–P network, yielding the highest compressive strength. In contrast, acid-rich systems exhibit divergent flexural and compressive behaviors, with enhanced flexural strength linked to hydrated silica domains arising from metakaolin dealumination, quantitatively tracked by ²⁹Si MAS NMR. XRPD further reveals the formation of uncommon Si–P crystalline phases (SiP₂O₇, Si₅P₆O₂₅) under low-temperature curing in acid-rich compositions. Together, these findings provide new insights into the nanoscale structuring, phase evolution, and stoichiometric control of silica–alumino–phosphate geopolymers, highlighting strategies for optimizing their performance in demanding thermal and chemical environments. Full article

Background/Objectives: Cancer immunotherapy has revolutionized the field of oncology by harnessing the immune system to attack cancer cells, increasing survival in a broad spectrum of malignancies. However, despite its positive therapeutic benefit, immunotherapy is also associated with a spectrum of adverse events affecting various vital organs, including the cardiovascular system. Methods: We conducted a comprehensive review of the available literature on the epidemiology, pathophysiological mechanisms, and current management approaches for cardiovascular adverse events associated with cancer immunotherapy. In addition, we evaluated emerging personalized strategies and interventions aimed at mitigating these risks and improving patient outcomes. Results: Immunotherapy is associated with a broad spectrum of potentially serious cardiovascular adverse events, including immune-mediated myocarditis, heart failure, arrhythmias, pericarditis, and accelerated atherosclerosis. Among these, immune checkpoint inhibitor-associated myocarditis is the most well characterized and potentially fatal form of cardiotoxicity, with reported mortality rates approaching 50%. Similarly, chimeric antigen receptor T-cell therapy, despite its powerful antitumor efficacy, is frequently associated with cytokine release syndrome—a profound immune activation that can lead to significant systemic and cardiovascular complications. In response to these challenges, several personalized strategies are currently under development, including artificial intelligence and machine learning approaches, genetic and transcriptomic profiling, novel biomarker discovery, and integrated risk scoring systems, all aimed at enhancing risk stratification and improving patient care. Conclusions: Cancer immunotherapy has been associated with a range of immune-related cardiac adverse events, both non-severe and severe. As such, it is critically important to adopt a personalized approach to patient management before, during, and after the administration of immunotherapy. Early recognition through heightened clinical vigilance, along with the implementation of individualized risk assessment tools, is essential for identifying patients at high risk of immunotherapy-induced cardiotoxicity. These strategies are imperative for optimizing patient outcomes and ensuring safe and effective cancer treatment. Full article

In recent times, copper oxide nanosheets (CONSs) have shown a broad spectrum of industrial uses due to their unique properties, including high electrical conductivity, surface-enhanced catalytic activity, etc. Therefore, industrial processes involved in their manufacture can give rise to airborne particulates. Several in vivo studies have reported toxicity of these nanoparticles due to their interactions with biological molecules. Generally, literature-based assessment of their toxicity has centered on experimental findings. In this paper, we report for the first time, trend in CONSs interactions in intracellular and extracellular fluids, using the Nonlinear Mean Field Poisson–Boltzmann theory. Our theoretical prediction for zeta potential in the extracellular fluid environment align with published values in the literature. Based on this theoretical approach, we also demonstrate that double layer disjoining pressure due to interacting double layers of CONSs is generally higher in intracellular fluids. The findings of our theoretical approach highlight the importance of predicting the extent of cellular uptake potential of CONSs in organs that are prone to such airborne environmental particulates. Full article

Micellar or mycelial membranes from medicinal mushrooms are self-growing fibrous polymeric biocomposites that are biocompatible, biodegradable, cost-effective, and environmentally friendly. In this study, the cultivation process for the medicinal mushrooms Ganoderma lucidum and Pleurotus ostreatus has been optimized via submerged cultivation to maximize growth and promote the formation of micellar membranes with high water-absorption capacity. Optimal growth conditions were achieved at an alkaline pH in a medium containing malt extract for G. lucidum, while for P. ostreatus, these were in a glucose-enriched medium. The hydrophilic underside of the micellar membranes led to a high-water uptake capacity. These membranes exhibited a broad spectrum of functional groups, thermal stability with decomposition temperatures above 260 °C, and a fibrous and porous structure. The micellar membranes from both mushrooms were additionally functionalized with mango peel extract (MPE), resulting in a uniform and gradual release profile, which is an important novelty. They also showed successful antimicrobial activity against Escherichia coli and Staphylococcus aureus growth. MPE-functionalized micellar membranes are, therefore, innovative biocomposites suitable for various biomedical applications. As they mimic the extracellular matrix of the skin, they are a promising material for tissue engineering, wound healing, and advanced skin materials applications. Full article

Due to its broad-spectrum antibacterial activity, norfloxacin (NOR) has been widely used over the past few decades. However, the residual NOR in aquatic ecosystems could pose risks to human health from bacteria with resistance genes that potentially cause serious infectious diseases. Herein, a series of bandgap-tunable Zn_xCd_1−xS (x = 0~1) solid solutions were hydrothermally synthesized and used for NOR photodegradation under visible light and natural sunlight. Benefitting from the suitable bandgap, band structure, and unique tetrapod shape nanostructure, the Zn_0.1Cd_0.9S solid solution exhibited the best photocatalytic activity, with high degradation efficiencies of 83.23% and 86.28% under visible light and natural sunlight, respectively, within 60 min, which is remarkable among reported Zn_xCd_1−xS-based photocatalysts and other materials. The in situ reactive-species trapping experiment revealed that holes (h⁺) were the primary species, and a possible photodegradation mechanism was thus suggested. Moreover, Zn_0.1Cd_0.9S also exhibited decent reusability and stability after five cycles of experiments. This work provides a comprehensive exploration of the application of bandgap-tunable Zn_xCd_1−xS solid solutions for NOR photodegradation under visible light and natural sunlight, demonstrating the promising application of as-synthesized Zn_0.1Cd_0.9S in the photocatalytic degradation of antibiotics. Full article

Background/Objectives: Ceftaroline (CPT) is a broad-spectrum, fifth-generation cephalosporin with in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Streptococcus pneumoniae. Real-world data on its use in pediatric patients remain limited. This study aimed to the describe clinical characteristics and outcomes associated with CPT use in pediatric patients at a pediatric academic medical center. Methods: This retrospective case series evaluated patients under 18 years of age who received CPT between November 2016 and August 2023. The primary outcome was clinical success, defined as a composite of 30-day survival, absence of microbiological recurrence within 30 days, and/or resolution of acute infection signs and symptoms without therapy modification due to clinical failure. The secondary outcomes included adverse effects potentially attributable to CPT and the clinical rationale guiding its use. Results: Among 25 patients, most were male (68%) with a median (IQR) age of 3.4 (1.4–14.3) years. The indications for use commonly included respiratory infections (48%), bacteremia (16%), and/or skin and soft tissue (12%) infections. The frequently used dosing regimens included 12 mg/kg (36%) and 8 mg/kg (28%) q8hr, with a median (IQR) duration of therapy of 4.6 (1.7–10.0) days. Clinical success was achieved in 96% of patients. No adverse effects attributable to CPT were observed and CPT was commonly used for escalation (40%) and/or issues with alternative therapies (36%). Conclusions: CPT use was associated with high clinical success rates and no observed adverse effects in this pediatric report. These findings support its use as a therapeutic option when the alternatives are limited. Larger multicenter studies are needed to further evaluate the clinical outcomes and safety of CPT use in pediatric patients. Full article

Speed breeding technology has been used as a promising approach to accelerate plant breeding cycles and enhance agricultural productivity. However, systematic research on optimizing speed breeding conditions for alfalfa (Medicago sativa L.) in controlled plant factory environments remains limited. This study aimed to optimize light intensity, nutrient solution formulations, and photoperiod conditions for alfalfa speed breeding in plant factories equipped with full-spectrum LEDs, and to validate the applicability of these conditions across cultivars with different fall dormancy levels. Results demonstrated that a light intensity of 250 μmol·m⁻²·s⁻¹ significantly enhanced photosynthetic parameters, antioxidant enzyme activities, and biomass accumulation while minimizing malondialdehyde (MDA). The 75% concentration of the Japanese garden-test formula (JGTF) outperformed the Hoagland solution in promoting growth and photosynthetic pigment synthesis. An extended photoperiod (22 h/d) substantially accelerated growth and shortened flowering time. Under optimized conditions (250 μmol·m⁻²·s⁻¹ light intensity, 22 h/d photoperiod, and 75% Japanese Garden Test Formula), alfalfa cultivars reached initial flowering in approximately 37 days, regardless of fall dormancy level. This study establishes an effective speed breeding protocol for alfalfa, and the optimized conditions demonstrate broad applicability across cultivars with varying fall dormancy characteristics, providing a valuable foundation for accelerated alfalfa breeding programs and contributing to enhanced forage crop development efficiency. Full article

Biological control serves as a crucial strategy for crop disease management. The biocontrol potential and plant growth-promoting effects of the strain YTBTa14 were investigated. Genetic sequencing confirmed YTBTa14 as Pseudomonas chlororaphis, which exhibited broad-spectrum antifungal activity against multiple pathogens affecting grapevine, apple, cherry, and wheat. YTBTa14 significantly enhanced the growth of wheat and grapevine, specifically increasing wheat seed germination rates and improving root and coleoptile development. In grapevine plant, significant increases in root length, stem length, and fresh weight were observed. The strain demonstrated robust adaptability and stable antagonism under varying sodium chloride (NaCl) concentrations, pH levels, and temperatures. YTBTa14 modulated plant hormone levels, elevating the content of indole-3-acetic acid (IAA), gibberellins (GA), and cytokinins (CTK). Furthermore, it effectively stimulated the production of key plant defense enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Pretreatment of grape leaves with YTBTa14 triggered plant cell defense response and upregulated the expression of defense-related genes PR1 (pathogenesis-related protein 1) and PAL1 (phenylalanine ammonia-lyase 1), thereby mitigating the severity of downy mildew disease and inducing systemic resistance. These findings demonstrate that YTBTa14 is a highly promising candidate for development as a multifunctional agricultural biocontrol agent. Full article

Marine natural products have gained increasing interest in drug research and development because of their unique structures, diverse biological activities, and novel mechanisms of action. Using the antiviral alkaloid aldisine as the lead compound and utilizing the hydrogen bond effects common in drug design, novel derivatives containing an acylhydrazone moiety were designed and synthesized. The structures of these derivatives were systematically analyzed using variable-temperature ¹H-NMR. Antiviral activity tests showed that most derivatives were active against tobacco mosaic virus (TMV), with some compounds outperforming the commercial antiviral drug ribavirin. Notably, 3-methylphenyl- and 3-pyridyl-substituted acylhydrazones 5-6 and 5-12 displayed activity comparable to ningnanmycin, one of the most effective commercial antiviral agents. Molecular docking results indicated that incorporating the acylhydrazone moiety enhances hydrogen bonding between the molecules and target proteins. Additionally, we evaluated the fungicidal and larvicidal activities of these derivatives. Most exhibited significant larvicidal effects against Mythimna separata and Plutella xylostella, along with broad-spectrum fungicidal activity. Four related compounds (5-11, 5-12, 5-13, and 5-17) exhibited high fungicidal activities, and another four compounds (2-4, 5-6, 5-13, and 5-17) exhibited high larvicidal activities. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Cyclaniliprole is a novel third-generation anthranilic diamide insecticide which has broad-spectrum efficacy against various pests, including aphids. Rhopalosiphum padi and Schizaphis graminum are the two primary aphid species that infest wheat crops. This investigation evaluates cyclaniliprole’s acute toxicity and sublethal and transgenerational effects on both aphid species. The acute toxicity assessment revealed obvious insecticidal activity, with 24 h LC₅₀ values of 38.56 mg/L for R. padi and 33.71 mg/L for S. graminum. Sublethal exposure (LC₁₅ and LC₃₅ in R. padi; LC₃₅ in S. graminum) significantly reduced adult longevity and fecundity in the F₀ generation. In the F₁ generation, cyclaniliprole at LC₃₅ significantly reduced the fourth nymph stage in R. padi, whereas at LC₁₅, it shortened the third nymph stage duration in S. graminum compared to the control. Sublethal concentrations (LC₁₅ and LC₃₅) of cyclaniliprole significantly reduced age-stage-specific survival rate (s_xj), age-specific survival rate (l_x), age-specific maternity (l_xm_x), and age-stage life expectancy (e_xj) in the F₁ generation of R. padi, while only LC₃₅ decreased l_x, l_xm_x, and e_xj in S. graminum. Additionally, LC₃₅ significantly reduced the net reproductive rate (R₀) in the F₁ generation of R. padi compared to the control. These findings suggest that cyclaniliprole exhibit notable acute toxicity against both aphid species and that sublethal concentrations adversely affected the F₀ generation, with no observed hormetic effects in the F₁ generations of R. padi and S. graminum. The findings offer valuable insights for assessing the comprehensive insecticidal potential of cyclaniliprole. Full article