Search Results (2,059)

Antibiotic resistance is considered to be one of the most complex health obstacles of our time. Methicillin-resistant Staphylococcus aureus (MRSA) represents a global health challenge due to its broad treatment resistance capacity, resulting in high mortality rates. The shikimate pathway (SP) is responsible for the biosynthesis of chorismate from glycolysis and pentose phosphate pathway intermediates. This pathway plays a crucial role in producing aromatic amino acids, folates, ubiquinone, and other secondary metabolites in bacteria. Notably, SP is absent in humans, which makes it a specific and potential therapeutic target to explore for discovering new antibiotics against MRSA. The present study characterized in vitro and in silico natural products as inhibitors of the shikimate dehydrogenase from methicillin-resistant S. aureus (SaSDH). The results showed that, from the set of compounds studied, phloridzin, rutin, and caffeic acid were the most potent inhibitors of SaSDH, with IC₅₀ values of 140, 160, and 240 µM, respectively. Furthermore, phloridzin showed a mixed-type inhibition mechanism, whilst rutin and caffeic acid showed non-competitive mechanisms. The structural characterization of the SaSDH–inhibitor complex indicated that these compounds interacted with amino acids from the catalytic site and formed stable complexes. In biological activity studies against MRSA, caffeic acid showed an MIC of 2.2 mg/mL. Taken together, these data encourage using these compounds as a starting point for developing new antibiotics based on natural products against MRSA. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Nitrogen (N) fertilizer management in winter wheat production faces challenges from volatilization losses and sub-optimal application strategies. This is particularly problematic in the Southern Great Plains, where environmental conditions during top-dressing periods favor N losses. This study evaluated the effects of a fertilizer placement method, enhanced-efficiency fertilizers, and application timing on grain yield and protein concentration (GPC) across six site-years in Oklahoma (2016–2018). Treatments included broadcast applications of untreated urea and SuperU^® (urease/nitrification inhibitor-treated urea). These were compared with subsurface placement using single-disc and double-disc drilling systems, applied at 67 kg N ha⁻¹ during January, February, or March. Subsurface placement increased the grain yield by 324–391 kg ha⁻¹ compared to broadcast applications at sites with favorable soil conditions. However, responses varied significantly across environments. Enhanced-efficiency fertilizers showed limited advantages over untreated urea. Benefits were most pronounced during February applications under conditions favoring volatilization losses. Application timing effects were more consistent for GPC than for the yield. Later applications (February–March) increased GPC by 0.8–1.2% compared to January applications. Treatment efficacy was strongly influenced by soil pH, equipment performance, and post-application environmental conditions. This indicates that N management benefits are highly site-specific. These findings demonstrate that subsurface placement can improve nitrogen use efficiency (NUE) under appropriate conditions. However, success depends on matching application strategies to local soil and environmental factors rather than adopting universal recommendations. Full article

Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article

The precise synthesis of non-precious metal single-atom electrocatalysts is crucial for enhancing the yield of highly active reactive oxygen species (ROSs). Conventional oxidation methods, such as Fenton or NaClO processes, suffer from poor efficiency, high energy demand, and secondary pollution. In contrast, heterogeneous electro-Fenton systems based on cascade oxygen reduction reactions (ORRs), which require low operational voltage and cause pollutant degradation through both direct electron transfer and ROS generation, have emerged as a promising alternative. Recent studies showed that carbon cathodes decorated with atomically dispersed transition metals can effectively integrate the excellent conductivity of carbon supports with the tunable surface chemistry of metal centers. However, the electronic structure of active sites intrinsically hinders the simultaneous achievement of high activity and selectivity in cascade ORRs. This review summarizes the advances, specifically from 2020 to 2025, in understanding the mechanism of cascade ORRs and the synthesis of transition metal-based single-atom catalysts in cathode electrocatalysis for efficient wastewater treatment, and discusses the key factors affecting treatment performance. While employing atomically engineered cathodes is a promising approach for energy-efficient wastewater treatment, future efforts should overcome the barriers in active site control and long-term stability of the catalysts to fully exploit their potential in addressing water pollution challenges. Full article

Since carbohydrate antigen 19-9 (CA 19-9) is a significant biomarker for the clinical diagnosis and treatment of pancreatic cancer, a sensitive sandwich-type immunosensor was proposed with an epoxy functionalized covalent organic framework (EP-COF_TTA-DHTA) as the antibody carrier and an electroactive COF_{TTA-2,6-NA(OH)2} as the signal amplification probe for the sensitive detection of CA 19-9. The flexible covalent linkage between the epoxy-functionalized EP-COF_TTA-DHTA and the antibodies was employed to improve the dynamics of the antigen–antibody interaction significantly. Meanwhile, AuNPs@COF_{TTA-2,6-NA(OH)2} with abundant electroactive sites enhanced the current response of the immunoreaction significantly. After optimizing the incubation time and concentration of the antibody, CA 19-9 was quantitatively detected by differential pulse voltammetry (DPV) based on the sensitive sandwich-type immunosensor with a low detection limit of 0.0003 U/mL and a wide linear range of 0.0009–100 U/mL. The electrochemical immunosensor exhibits high specificity, stability and repeatability, and it provides a feasible and efficient method for the pathologic analysis and treatment of tumor markers. Full article

Background/Objectives: Brain metastasis (BM) is a common and often early manifestation in lung adenocarcinoma (LUAD), yet its tumor microenvironment remains poorly defined at the time of initial diagnosis. This study aims to characterize early immune microenvironmental alterations in synchronous BM using spatial proteomic profiling. Methods: We performed digital spatial proteomic profiling using the NanoString GeoMx platform on formalin-fixed paraffin-embedded tissues from five treatment-naïve LUAD patients in whom BM was the initial presenting lesion. Paired primary lung and brain metastatic samples were analyzed across tumor and stromal compartments using 68 immune- and tumor-related protein markers. Results: Spatial profiling revealed distinct expression patterns between primary tumors and brain metastases. Immune regulatory proteins—including IDO-1, PD-1, PD-L1, STAT3, PTEN, and CD44—were significantly reduced in brain metastases (p < 0.01), whereas pS6, a marker of activation-induced T-cell death, was significantly upregulated (p < 0.01). These alterations were observed in both tumor and stromal regions, suggesting a more immunosuppressive and apoptotic microenvironment in brain lesions. Conclusions: This study provides one of the first spatially resolved proteomic characterizations of synchronous BM at initial LUAD diagnosis. Our findings highlight early immune escape mechanisms and suggest the need for site-specific immunotherapeutic strategies in patients with brain metastasis. Full article

Nanotechnology is revolutionizing medicine by enabling highly precise diagnostics, targeted therapies, and personalized healthcare solutions. This review explores the multifaceted applications of nanotechnology across medical fields such as oncology and infectious disease control. Engineered nanoparticles (NPs), such as liposomes, polymeric carriers, and carbon-based nanomaterials, enhance drug solubility, protect therapeutic agents from degradation, and enable site-specific delivery, thereby reducing toxicity to healthy tissues. In diagnostics, nanosensors and contrast agents provide ultra-sensitive detection of biomarkers, supporting early diagnosis and real-time monitoring. Nanotechnology also contributes to regenerative medicine, antimicrobial therapies, wearable devices, and theranostics, which integrate treatment and diagnosis into unified systems. Advanced innovations such as nanobots and smart nanosystems further extend these capabilities, enabling responsive drug delivery and minimally invasive interventions. Despite its immense potential, nanomedicine faces challenges, including biocompatibility, environmental safety, manufacturing scalability, and regulatory oversight. Addressing these issues is essential for clinical translation and public acceptance. In summary, nanotechnology offers transformative tools that are reshaping medical diagnostics, therapeutics, and disease prevention. Through continued research and interdisciplinary collaboration, it holds the potential to significantly enhance treatment outcomes, reduce healthcare costs, and usher in a new era of precise and personalized medicine. Full article

Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article

Soil acidity is one of the main limiting factors for coffee production in Peruvian rainforests. The objective of this study is to predict the spatial acidity variability for recommending site-specific liming and phosphorus fertilization treatments. We analyzed thirty-six edaphoclimatic variables, eight methods for estimating liming doses, and three geospatial variables from 552 soil samples in the Pichanaqui district of Peru. Multivariate statistics, nonparametric comparison, and geostatistical analysis with Ordinary Kriging interpolation were used for data analysis. The results showed low coffee yields (0.70 ± 0.16 t ha⁻¹) due to soil acidification. The interquartile ranges (IQR) were found to be 3.80–5.10 for pH, 0.21–0.87 cmol Kg⁻¹ for Al⁺³, and 2.55–6.53 mg Kg⁻¹ for available P, which are limiting soil conditions for coffee plantations. Moreover, pH, Al⁺³, Ca⁺², and organic matter (OM) were the variables with the highest accuracy and quality in the spatial prediction of soil acidity (R² between 0.77 and 0.85). The estimation method of liming requirements, MPM (integration of pH and organic material method), obtained the highest correlation with soil acidity-modulating variables and had a high spatial predictability (R² = 0.79), estimating doses between 1.50 and 3.01 t ha⁻¹ in soils with organic matter (OM) > 4.00%. The MAC (potential acidity method) method (R² = 0.59) estimated liming doses between 0.51 and 0.88 t ha⁻¹ in soils with OM < 4.00% and potential acidity greater than 0.71 cmol Kg⁻¹. Regarding phosphorus fertilization (DAP), the results showed high requirements (median = 137.21 kg ha⁻¹, IQR = 8.28 kg ha⁻¹), with high spatial predictability (R² = 0.74). However, coffee plantations on Ferralsols, with Paleogene parental material, mainly in dry forests, had the lowest predicted fertilization requirements (between 6.92 and 77.55 kg ha⁻¹ of DAP). This research shows a moderate spatial variation of acidity, the need to optimize phosphorus fertilization, and an optimal prediction of liming requirements using the MPM and MAC methods, which indicate high requirements in the southwest of the Pichanaqui district. Full article

The heavy metal contamination of soils is a global environmental challenge threatening water quality, food safety, and human health. Using a systematic literature review approach, this study aimed to assess the potential of bacterial strains to immobilize cadmium (Cd²⁺), lead (Pb²⁺), and copper (Cu²⁺) in contaminated soils. A total of 45 articles were analyzed, focusing on studies that reported heavy metal concentrations before and after bacterial treatment. The analysis revealed that bacterial genera such as Bacillus, Pseudomonas, and Enterobacter were most commonly used for the immobilization of these metals. Immobilization efficiencies ranged from 25% to over 98%, with higher efficiencies generally observed when microbial consortia or amendments (e.g., phosphate compounds and biochar) were applied. The main immobilization mechanisms included biosorption, bioprecipitation (such as carbonate-induced precipitation), bioaccumulation, and biomineralization, which convert mobile metal ions into more stable, less bioavailable forms. These findings highlight the promising role of microbial-assisted immobilization in mitigating heavy metal pollution and reducing ecological risks. Further laboratory and field studies are needed to optimize the use of these microbial strains under site-specific conditions to ensure effective and sustainable soil remediation practices. Full article

The primary aim of this study was to explore the influence of abiotic factors on weed development in maize fields, with the goal of informing more effective weed management practices. We focused on identifying key environmental, edaphic, and agricultural variables that contribute to weed infestations, particularly before the application of spring herbicide treatments. Field investigations were conducted from 2018 to 2021 across selected maize-growing regions in Hungary. Over the four-year period, a total of 51 weed species were recorded, with Echinochloa crus-galli, Chenopodium album, Portulaca oleracea, and Hibiscus trionum emerging as the most prevalent taxa. Collectively, these four species accounted for more than half (52%) of the total weed cover. Altogether, the 20 most dominant species contributed 95% of the overall weed coverage. The analysis revealed that weed cover, species richness, and weed diversity were significantly affected by soil properties, nutrient levels, geographic location, and tillage systems. The results confirm that the composition of weed species was influenced by several environmental and management-related factors, including soil parameters, geographical location, annual precipitation, tillage method, and fertilizer application. Environmental factors collectively explained a slightly higher proportion of the variance (13.37%) than farming factors (12.66%) at a 90% significance level. Seasonal dynamics and crop rotation history also played a notable role in species distribution. Nutrient inputs, particularly nitrogen, phosphorus, and potassium, influenced both species diversity and floristic composition. Deep tillage practices favored the proliferation of perennial species, whereas shallow cultivation tended to promote annual weeds. Overall, the composition of weed vegetation proved to be a valuable indicator of site-specific soil conditions and agricultural practices. These findings underscore the need to tailor weed management strategies to local environmental and soil contexts for sustainable crop production. Full article

Untreated sewage sludge (SS) and misused stabilization technologies have contributed to great contamination and the accumulation of various pollutants in agricultural soils. Regarding micro-pollutants’ degradation, scalable and effective technologies are still scarce. Although many attempts at composting adaptations have been discussed, only a few have been tested individually under outdoor conditions. To investigate different composting methods (bioaugmentation and semipermeable cover) for the removal of micro-pollutants frequently found in SS, we performed a set of on-site experiments. Windrows of SS and olive pruning were used as the compostable material and were subjected to (i) bioaugmentation with the fungus Penicillium oxalicum, (ii) covered composting, (iii) covered and bioaugmented composting, and (iv) a conventional composting pile, which was included as a control. The entire experiment lasted 99 days. Bioaugmentation without cover increased the phosphorus content, favored a reduction in heavy metal content, and was the only treatment that reduced carbamazepine at the end of the process. Moreover, the inoculation of P. oxalicum under semipermeable cover increased the richness, diversity, and dominance of specific microbial taxa and total bacterial abundance. The four mature composts obtained met the standards required to be classified in the B fertilizer category, showing that we reduced most of the micro-pollutants, and passed the germination test. Full article

Limited molecular data exist on zoonotic parasites Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Angus calves from Guizhou, China. This study constitutes the first molecular epidemiological survey of these pathogens in this region. 817 fecal samples from Angus calves across 7 intensive beef farms (Bijie City). Nested PCR methods targeting SSU rRNA (Cryptosporidium spp.), gp60 (Cryptosporidium bovis subtyping), bg/gdh/tpi (G. duodenalis), and ITS (E. bieneusi) coupled with DNA sequencing were employed. DNA sequences were analyzed against the NCBI. database. Statistical differences were assessed via a generalized linear mixed-effects model. Cryptosporidium spp. prevalence 23.5% (192/817; 95% CI 28.1–34.6%), with C. bovis predominating 89.6% (172/192; 95% CI 84.4–93.5%) and six subtypes (XXVIa-XXVIf). Highest infection in 4–8-week-olds 29.9% (143/479; 95% CI 25.8–34.1%) (p < 0.01). G. duodenalis: 31.3% (256/817; 95% CI 28.1–34.6%) positive, overwhelmingly assemblage E 97.6% (6/256; 95% CI 0.9–5.0%), zoonotic assemblage A was marginal 0.7% (6/817; 95% CI 0.3–1.6%). Farm-level variation exceeded 10-fold (e.g., Gantang: 55.0% (55/100; 95% CI 44.7–65.0%) vs. Tieshi: 4.9% (5/102; 95% CI 1.6–11.1%). E. bieneusi: prevalence 19.7% (161/817; 95% CI 17.0–22.6%), exclusively zoonotic genotypes BEB4: 49.7% (80/161; 95% CI 41.7–57.7%); I: 40.4% (65/161; 95% CI 32.7–48.4%). Strong diarrhea association (p < 0.01) and site-specific patterns (e.g., Guanyindong: 39.2%). While Giardia exhibited the highest prevalence (31.3%) with minimal zoonotic risk, Enterocytozoon—despite lower prevalence (19.7%)—posed the greatest public health threat due to exclusive circulation of human-pathogenic genotypes (BEB4/I) and significant diarrhea association, highlighting divergent control priorities for these enteric parasites in Guizhou calves. Management/Public health impact: Dominant zoonotic E. bieneusi genotypes (BEB4/I) necessitate: 1. Targeted treatment of 4–8-week-old Angus calves. 2. Manure biofermentation (≥55 °C, 3 days), and 3. UV-disinfection (≥1 mJ/cm²) for karst water to disrupt transmission in this high-humidity region. Full article

Equine lutropin hormone/choriogonadotropin receptor (LH/CGR) is a G protein-coupled receptor that binds to both luteinizing hormone and choriogonadotropin, with multiple potential N-linked glycosylation sites in the long extracellular domain region. The roles of these glycosylation sites in hormone binding have been widely studied; however, their relationships with cyclic adenosine monophosphate (cAMP) activation, loss of cell surface receptors, and phosphorylated extracellular signal-regulated kinases1/2 (pERK1/2) expression are unknown. We used site-directed mutagenesis with the substitution of Asn for Gln to alter the consensus sequences for N-linked glycosylation, and cAMP signaling was analyzed in the mutants. Specifically, the N174Q and N195Q mutants exhibited markedly reduced expression levels, reaching approximately 15.3% and 2.5%, respectively, of that observed for wild-type equine LH/CGR. Correspondingly, the cAMP EC₅₀ values were decreased by 7.6-fold and 5.6-fold, respectively. Notably, the N195Q mutant displayed an almost complete loss of cAMP activity, even at high concentrations of recombinant eCG, suggesting a critical role for this glycosylation site in receptor function. Despite these alterations, Western blot analysis revealed that pERK1/2 phosphorylation peaked at 5 min following agonist stimulation across all mutants, indicating that the ERK1/2 signaling pathway remains functionally intact. This study demonstrates that the specific N-linked glycosylation site, N195, in equine LH/CGR is indispensable for cAMP activity but is normally processed in pERK1/2 signaling. Thus, we suggest that in equine LH/CGR, agonist treatment induces biased signaling, differentially activating cAMP signaling and the pERK1/2 pathway. Full article