Search Results (28,994)

The Mycoplasmataceae are a family of bacteria that typically cause respiratory, arthritic, and genitourinary disease in humans. Mycoplasma spp. of animal origin are also the causative agents of porcine wheezing disease, chronic respiratory disease and arthritis in chickens and other conditions. These diseases have a significant impact on public health and the economic development of livestock breeding. Clinical prevention and treatment of mycoplasma infections is primarily dependent on the use of antibiotics. However, inappropriate and excessive use of antimicrobials has enabled resistance development that has become a significant clinical concern. Mycoplasma are also robust biofilm producers, and this process is a major factor for the persistence of these infections, especially in conjunction with common antibiotic resistance mechanisms, including target gene mutations and the action of efflux pumps. A mycoplasma biofilm refers to a structured and stable microbial community formed by Mycoplasma spp. adhering to biological or non-biological surfaces under suitable conditions and secreting extracellular polymers (EPS) such as polysaccharides. This process allows the microorganisms to adapt to their surrounding environment and survive during the growth process. These biofilms render bacteria more resistant to antimicrobials than planktonic bacteria, resulting in biofilm-associated infections that are more challenging to eradicate and more likely to recur. The current study reviews progress from the fields of biofilm formation, structure and identification, correlations between biofilms and drug resistance and virulence as well as methods of biofilm prevention and control. Our aim was to provide a reference basis for the subsequent in-depth understanding of the research of mycoplasma biofilms. Full article

Background: Small airway dysfunction (SAD) plays a critical role in the management of severe asthma, particularly in patients at risk of requiring biological therapies (BTs). Short-term studies have shown that switching to single-inhaler triple therapy (SITT) with extrafine beclomethasone–formoterol–glycopyrronium improves outcomes and helps achieve quiet asthma, a state marked by symptom control, no exacerbations or oral steroids, reduced inflammation, and better small airway function. This study investigated whether, over one year, patients could maintain this state as Steady Quiet Asthma (SQA) and whether baseline measures could predict this sustained response. Methods: Twenty-six patients with severe asthma and SAD were transitioned from open triple-inhaler therapy to a closed, single-inhaler triple therapy containing extrafine beclomethasone–formoterol–glycopyrronium. Assessments at baseline (T0) and at one-year follow-up (T12) included clinical evaluations, spirometry, and impulse oscillometry, with a focus on Fres as a predictor for the need for BT. When prescribed, biologic therapies included mepolizumab, benralizumab, and dupilumab. Results: Of the 26 patients, 9 (34.6%) achieved SQA and did not require biologic therapy at the one-year follow-up, while 17 patients (65.4%) initiated biologic treatment. At T0, patients who required biologics had significantly higher median Fres (21 (19.47; 24.58) vs. 17.61 (15.82; 20.63); p = 0.049) compared to those who remained biologic-free. They also exhibited higher residual volume to total lung capacity ratio (%RV/TLC) values and lower forced expiratory volume in one second/forced vital capacity ratios (FEV₁/FVC). At T12, patients spared from BT showed significant reductions in Fres (p = 0.014) and improvements in small airway function (difference in airway resistance between 5 Hz and 20 Hz (R5–20), forced expiratory flow between 25% and 75% of FVC (%FEF25–75), and better asthma control (ACT). In contrast, patients on BT demonstrated less favorable changes in these parameters. Conclusions: Baseline Fres, FEV1/FVC ratio, and %FEV25–75 are valuable predictors of achieving Steady Quiet Asthma (SQA) and sparing biologic therapy. These findings support the use of SITT in severe asthma and highlight the importance of early functional assessments to guide personalized management. Full article

In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, physicochemical property characterization of the encoded proteins, subcellular localization prediction, phylogenetic reconstruction, chromosomal mapping, promoter cis-element analysis, and comprehensive expression profiling using transcriptomic data and qRT-PCR (including tissue-specific expression, hormone treatments, and Fusarium oxysporum infection assays). A total of 107 GH19 genes were identified across the four species (35 in G. barbadense, 37 in G. hirsutum, 19 in G. arboreum, and 16 in G. raimondii). The molecular weights of GH19 proteins ranged from 9.9 to 97.3 kDa, and they were predominantly predicted to localize to the extracellular space. Phylogenetic analysis revealed three well-conserved clades within this family. In tetraploid cotton, GH19 genes were unevenly distributed across 12 chromosomes, often clustering in certain regions, whereas in diploid species, they were confined to five chromosomes. Promoter analysis indicated that GH19 gene promoters contain numerous stress- and hormone-responsive motifs, including those for abscisic acid (ABA), ethylene (ET), and gibberellin (GA), as well as abundant light-responsive elements. The expression patterns of GH19 genes were largely tissue-specific; for instance, GbChi23 was predominantly expressed in the calyx, whereas GbChi19/21/22 were primarily expressed in the roots and stems. Overall, this study provides the first comprehensive genomic and functional characterization of the GH19 family in G. barbadense, laying a foundation for understanding its role in disease resistance mechanisms and aiding in the identification of candidate genes to enhance plant defense against biotic stress. Full article

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis and limited therapeutic options. Background/Objectives: Integrin α_vβ₃, a cell surface receptor overexpressed in GBM, specifically binds to cyclic arginine-glycine-aspartate-D-phenylalanine-lysine (c(RGDfK)) motif, making it a valuable target for tumor-specific delivery and PET imaging. This study explores a novel radiotheranostic agent, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK), which combines the imaging and therapeutic capabilities of copper-64 (⁶⁴Cu) and the cytotoxic activity of a terpyridine-platinum (TP) complex, conjugated to c(RGDfK). Methods: A robust protocol was developed for the small-scale preparation of NOTA-TP-c(RGDfK). Comparative cellular studies were conducted using U87 MG glioblastoma (GBM) cells and SVG p12 human astrocytes to evaluate the performance of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) relative to [⁶⁴Cu]Cu-NOTA-c(RGDfK), [⁶⁴Cu]Cu-NOTA-TP, ^natCu-NOTA-TP-c(RGDfK), cisplatin, and temozolomide. Results: ⁶⁴Cu-radiolabeling of NOTA-TP-c(RGDfK) was achieved with >99% radiochemical purity, and competition assays confirmed high binding affinity to integrin α_vβ₃ (IC₅₀ = 16 ± 8 nM). Cellular uptake, internalization, and retention studies demonstrated significantly higher accumulation of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) in U87 MG cells compared to control compounds, with 38.8 ± 1.8% uptake and 28.0 ± 1.0% internalization at 24 h. Nuclear localization (6.0 ± 0.5%) and stable intracellular retention further support its therapeutic potential for inducing localized DNA damage. Importantly, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) exhibited the highest cytotoxicity in U87 MG cells (IC₅₀ = 10 ± 2 nM at 48 h), while maintaining minimal toxicity in normal SVG p12 astrocytes. Conclusions: These results highlight [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) as a promising targeted radiotheranostic agent for GBM, warranting further preclinical development Full article

Alloys and metals exhibit high sensitivity to corrosion and aggressive environments. Hence, the development of protective treatments through accessible methods with a high degree of protection has become a necessity. This paper presents a method for treating the hydrophilic surface of aluminum alloys using two types of unsaturated fatty acids, thereby increasing the degree of hydrophobicity and protecting the material. The samples were cleaned by a chemical process, followed by immersion in oleic acid (C₁₈H₃₄O₂, 18:1 cis-9) and elaidic acid (C₁₈H₃₄O₂, 18:1 trans-9), and they were then treated at a temperature of 80 °C. Morphological and microstructural analyses were conducted using OM, FE-SEM, EDX, and FTIR to understand the influence of unsaturated monocarboxylic fatty acids on the alloy surfaces. The wettability capacity of the alloys was investigated by measuring the contact angle (CA). The results revealed that the cleaning step and modification treatment with fatty acids are essential steps for increasing the hydrophobic character of the surface. This study can be applied to various types of metallic substrates to enhance their corrosion resistance and long-term chemical stability in aggressive environments, making it adaptable for use in different industrial fields. Full article

Alkyladenine DNA glycosylase (AAG) is a critical enzyme in the base excision repair (BER) pathway, responsible for removing a broad spectrum of alkylated DNA lesions. While AAG maintains genomic stability, dysregulated activity has been implicated in cancer development, drug resistance, and neurodegenerative diseases. This review synthesizes the current knowledge on AAG’s structure, catalytic mechanism, and polymorphic variants, highlighting their potential roles in disease pathogenesis. A comprehensive bioinformatics analysis of over 370 AAG single-nucleotide polymorphisms (SNPs) is presented, identifying ~40% as high-risk variants likely to impair enzymatic function. Notably, 151 SNPs were predicted to be damaging by multiple algorithms, including substitutions at catalytic residues and non-conserved sites with unknown functional consequences. Analysis of cancer databases (COSMIC, cBioPortal, NCBI) revealed 93 tumor-associated AAG variants, with 18 classified as high-impact mutations. This work underscores the need for mechanistic studies of AAG variants using structural biology, cellular models, and clinical correlation analyses. Deciphering AAG’s polymorphic landscape may unlock personalized strategies for cancer prevention and treatment. Full article

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

The ongoing global climate change has led to an increase in the frequency and complexity of drought events. Pinus yunnanensis, a native tree species in southwest China that possesses significant ecological and economic value, exhibits a high sensitivity to drought stress, particularly in its seedlings. This study investigates the response mechanisms of non-structural carbohydrates (NSCs, defined as the sum of soluble sugars and starch) and the stoichiometric characteristics of carbon (C), nitrogen (N), and phosphorus (P) to repeated drought conditions in Pinus yunnanensis seedlings. We established three treatment groups in a potting water control experiment involving 2-year-old Pinus yunnanensis seedlings: normal water supply (CK), a single drought (D1), and three drought–rewatering cycles (D3). The findings indicated that the frequency of drought occurrences, organ responses, and their interactions significantly influenced the non-structural carbohydrate (NSC) content and its fractions, as well as the C/N/P content and its stoichiometric ratios. Under D3 treatment, stem NSC content increased by 24.97% and 29.08% compared to CK and D1 groups (p < 0.05), respectively, while root NSC content increased by 41.35% and 49.46% versus CK and D1 (p < 0.05). The pronounced accumulation of soluble sugars and starch in stems and roots under D3 suggests a potential stress memory effect. Additionally, NSC content in the stems increased significantly by 77.88%, while the roots enhanced their resource acquisition by dynamically regulating the C/P ratio, which increased by 23.26% (p < 0.05). Needle leaf C content decreased (18.77%) but P uptake increased (8%) to maintain basal metabolism (p < 0.05). Seedling growth was N-limited (needle N/P < 14) and the degree of N limitation was exacerbated by repeated droughts. Phenotypic plasticity indices and principal component analysis revealed that needle nitrogen and phosphorus, soluble sugars in needles, stem C/N ratio (0.61), root C/N ratio (0.53), and stem C/P ratio were crucial for drought adaptation. This study elucidates the physiological mechanisms underlying the resilience of Pinus yunnanensis seedlings to recurrent droughts, as evidenced by their organ-specific strategies for allocating carbon, nitrogen, and phosphorus, alongside the dynamic regulation of nitrogen storage compounds (NSCs). These findings provide a robust theoretical foundation for implementing drought-resistant afforestation and ecological restoration initiatives targeting Pinus yunnanensis in southwestern China. Full article

Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In this report, we present a rare case of BORSA bacteremia and discuss potential approaches to improve its detection and management. Case presentation: A 39-year-old woman with systemic lupus erythematosus was admitted for a suspected exacerbation, complicated by multiple serositis and nephritis. She was on chronic treatment with methylprednisolone and hydroxychloroquine. On admission, she was afebrile. Laboratory investigations revealed elevated C-reactive protein and increased D-dimer levels. Later, she developed a septic peripheral venous thrombophlebitis, and treatment was adjusted to amoxicillin–clavulanate. Blood cultures grew S. aureus, prompting a switch to intravenous oxacillin based on a negative penicillin-binding protein 2a test. A discrepancy in the antimicrobial susceptibility test was observed, with cefoxitin showing susceptibility and oxacillin resistance. Further characterizations were carried out, confirming a BORSA infection. Treatment was switched to linezolid and ciprofloxacin with good recovery. Conclusions: This case highlights the complexity of managing a patient with an uncommon and poorly documented infection. The lack of data on BORSA infections and the difficulties in detecting and treating them led to a prolonged delay in the appropriate management of this patient. Full article

Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their antibacterial and anti-biofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) in combination with ampicillin sodium (AS) were analyzed. The PNPs had an average particle diameter of 118.0 nm, a polydispersity index of 0.129, and a zeta potential of −28.2 mV. The fractional inhibitory concentration indices of PNPs and AS against tested MRSA strains highlighted this synergy, ranging between 0.375 and 0.5. Crystal violet staining showed that combined PNPs and AS significantly inhibited biofilm formation and reduced existing biofilm biomass. We then discovered that PNPs inhibited bacterial adhesion, extracellular polysaccharide synthesis, and mecR1, mecA, blaZ, and icaADBC gene expression. These results indicated that PNPs exerted a synergistic antibacterial effect with AS by inhibiting mecR1, mecA, and blaZ gene expressions to reduce the drug resistance of MRSA. Meanwhile, PNPs weakened bacterial adhesion and aggregation by suppressing icaADBC gene expression, allowing antibiotics to penetrate the biofilm, and exhibiting significant synergistic anti-biofilm activity. In summary, PNPs are promising candidates for combating MRSA-related diseases. Full article

Superficial fungal infections of the feet, such as tinea pedis and onychomycosis, are highly prevalent and frequently recurrent, often due to persistent contamination of footwear, textiles, and foot care instruments. Despite growing concern over antifungal resistance, environmental sources of reinfection remain under-recognized in clinical practice. This review critically examines historical and contemporary methods used to sanitize shoes, socks, podiatric tools, and related materials. Evidence from peer-reviewed studies published between 1938 and 2025 was analyzed across multiple disinfection categories, including chemical agents, thermal methods, laundering, ultraviolet- and ozone-based technologies, antimicrobial textiles, and sterilization protocols. Findings reveal a range of efficacies, limitations, and practical considerations across methods, with steam sterilization emerging as the most reliable for reusable instruments. A multifaceted approach combining pharmacologic treatment with consistent environmental hygiene is essential for breaking reinfection cycles and reducing antifungal resistance. This review highlights the need for clinical education and research into scalable, effective disinfection strategies. Full article

One of the aggressive and lethal cancers, pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and resistance to conventional treatments. Moreover, the tumor immune microenvironment (TIME) plays a crucial role in the progression and therapeutic resistance of PDAC. It is associated with T-cell exhaustion, leading to the progressive loss of T-cell functions with an impaired ability to kill tumor cells. Therefore, this study employed single-cell RNA sequencing (scRNA-seq) analysis of a publicly available human PDAC dataset, with cells isolated from the primary tumor and adjacent normal tissues, identifying upregulated genes of T-cells and cancer cells in two groups (“cancer cells_vs_all-PDAC” and “cancer-PDAC_vs_all-normal”). Common and unique markers of cancer cells from both groups were identified. The Reactome pathways of cancer and T-cells were selected, while the genes implicated in those pathways were used to perform PPI analysis, revealing the hub genes of cancer and T-cells. The gene expression validation of cancer and T-cells hub-genes was performed using GEPIA2 and TISCH2, while the overall survival analysis of cancer cells hub-genes was performed using GEPIA2. Conclusively, this study unraveled 16 novel markers of cancer and T-cells, providing the groundwork for future research into the immune landscape of PDAC, particularly T-cell exhaustion. However, further clinical studies are needed to validate these novel markers as potential therapeutic targets in PDAC patients. Full article

Obesity, type 2 diabetes mellitus (T2DM) and steatohepatitis associated with metabolic dysfunction (MASLD) are on the rise and pose serious health challenges worldwide. In recent years, researchers have gained a better understanding of the important role of the gut microbiota in the development and progression of these diseases. Intestinal dysbiosis can contribute to the occurrence of increased intestinal permeability, inflammation and reduced numbers of commensal bacteria. In obesity, these changes contribute to chronic low-grade inflammation and deregulated metabolism. In MASLD, gut microbiota dysbiosis can promote liver fibrosis and impair bile acid metabolism, while in T2DM, they are associated with impaired glycemic control and insulin resistance. Regular physical activity has a positive effect on the composition of the gut microbiota, increasing its diversity, modulating its metabolic functions, strengthening the intestinal barrier and reducing inflammation. These findings suggest that exercise and microbiota-targeted interventions may play an important role in the prevention and treatment of metabolic diseases. Full article

Background: The emergence and spread of antimicrobial-resistant bacteria (ARB) has become an urgent global concern as a silent pandemic. When taking measures to reduce the impact of antimicrobial resistance (AMR) on the environment, it is important to consider appropriate treatment of wastewater from medical facilities. Methods: In this study, a continuous-flow wastewater treatment system using ozone and ultraviolet light, which has excellent inactivation effects, was implemented in a hospital in an urban area of Japan. Results: The results showed that 99% (2 log₁₀) of Gram-negative rods and more than 99.99% (>99.99%) of ARB comprising ESBL-producing Enterobacterales were reduced by ozone treatment from the first day after treatment, and ultraviolet light-emitting diode (UV-LED) irradiation after ozone treatment; UV-LED irradiation after ozonation further inactivated the bacteria to below the detection limit. Inactivation effects were maintained throughout the treatment period in this study. Metagenomic analysis showed that the removal of these microorganisms at the DNA level tended to be gradual in ozone treatment; however, the treated water after ozone/UV-LED treatment showed a 2 log₁₀ (>99%) removal rate at the end of the treatment. The residual antimicrobials in the effluent were benzylpenicillin, cefpodoxime, ciprofloxacin, levofloxacin, azithromycin, clarithromycin, doxycycline, minocycline, and vancomycin, which were removed by ozone treatment on day 1. In contrast, the removal of ampicillin and cefdinir ranged from 19% to 64% even when combined with UV-LED treatment. Conclusions: Our findings will help to reduce the discharge of ARB and antimicrobials into rivers and maintain the safety of aquatic environments. Full article