Search Results (530)

Phthalic acid esters (PAEs) are important plasticizers that have led to the heavy pollution of farmland, which has aroused significant and widespread concern for soil health and food safety. Microbial degradation has been recognized as an efficient pathway for removing PAEs from the environment. In this study, the PAE-degrading strain FR1 was isolated from sewage and determined to belong to Glutamicibacter. This strain degraded PAEs efficiently under a wide range of conditions—10–50 °C, pH of 6.0–11.0, and 0–8% salinity—demonstrating its great potential in PAE bioremediation. Genome sequencing provided complete genomic information, showing that the strain comprises one chromosome (3,404,214 bp) and three plasmids (112,089 bp, 80,486 bp, and 40,002 bp). The chromosome harbors 3238 protein genes, of which the PAE hydrolase genes dphGB1 and mphGB2 have been cloned. The hydrolase DphGB1 from hydrolase family I contained the catalytic triad Ser75-Asp194-His221. After heterogeneous expression and purification, the recombinant protein DphGB1, of about 30 kDa, was obtained. This hydrolase showed strong hydrolytic ability toward DEHP. The protein MphGB2 could also hydrolyze MBP. The molecular docking revealed interaction between DphGB1 and DBP. The main hydrolases of strain FR1-degrading PAEs were functionally identified. These results will promote the elucidation of the catalytic mechanisms of PAE hydrolases and the application of strain FR1 in farmland soil remediation. Full article

Distinct PAEs are implicated in breast cancer progression through multiple molecular pathways. This study aims to elucidate the potential mechanisms in common by which PAEs promote breast cancer progression. Dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethylhexyl phthalate (DEHP) were selected as representative PAE compounds. Network toxicology guided the construction of a regulatory network centered on five key transcription factor-associated genes: TP53, CTNNB1, PPARA, ESR1, and CDKN2A. Differential expression and survival analyses confirmed the significant impact of these hub genes on breast cancer (p < 0.05). Molecular docking results revealed direct interactions between the three PAEs and hub targets, while BBP had the strongest PAE-hub gene interaction and DEHP had the weakest one. Computer-aided molecular design (CAMD), combined with molecular docking, found the importance of alkyl chains and phenyl in PAE-hub gene interaction. A group addition/subtraction controlled experiment revealed that the binding affinities of modified BBP variants to hub genes are all weaker than the unmodified parent. The drop was significant whether the C17 alkyl chain was lengthened to match DEHP (p = 0.026) or the phenyl group was removed (p = 0.022). The findings provide novel insights into the mechanism in common of PAE-promoting breast cancer and offer a foundation for the unified intervention strategies and the design of safer plasticizer alternatives. Full article

Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF’s biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals. Full article

Dopamine D2-like receptors, including D2, D3, and D4, are members of the aminergic G protein-coupled receptor (GPCR) family and are targets for neurological disorders. The development of subtype selective ligands is important for enhanced therapeutics and reduced side effects; however, it is challenging to design and develop selective ligands owing to the high degree of sequence homology among D2-like subtypes. To gain insight into the structural basis of subtype selectivity of piperazinylalkyl pyrazole/isoxazole analogs for D2-like dopamine receptors, we carried out 3D quantitative structure–activity relationship (3D-QSAR) and molecular docking studies. The 3D-QSAR models for the D2, D3, and D4 subtypes showed robust correlation coefficients (r²) of 0.960, 0.912, and 0.946, as well as reliable predictive values (Q²) of 0.511, 0.808, and 0.560, respectively. Contour map analysis revealed key structural determinants for ligand activity, highlighting the distinct steric and electrostatic requirements for each subtype. These findings were further rationalized by molecular docking studies, which confirmed that interactions with non-conserved residues modulate binding affinity. Crucially, our analysis identified a critical structural basis for D4 subtype selectivity. This selectivity is attributed to a spatial constraint within the hydrophobic pocket formed by TMs 3, 5, and 6. This constraint restricts the orientation of bulky substituents on the 4-phenylpiperazine moiety. These findings provide actionable structural insights for the rational design of next-generation subtype-selective antagonists for D2-like dopamine receptors. Full article

N-polar GaN HEMT technology has emerged as a disruptive technology that outperforms Ga-polar GaN HEMTs in terms of high-frequency power amplification capability. In this paper, the authors present a comprehensive review of the evolution of N-polar GaN HEMT technology from the perspective of crystal growth, dielectrics, and metals on N-polar GaN, transistor design, and performance. Specifically, the authors discuss the progress of the N-polar GaN HEMTs toward high-frequency, high-power, and high-efficiency applications with recent record-level performances, demonstrated by the authors, at mmWave frequencies. Full article

Ecofriendly flame-retardant polystyrene (PS) composites were developed using the synergistic effects of phytic acid (PA), polyethyleneimine (PEI), and expandable graphite (EG). PA was chemically hybridized with PEI, and the hybrid (PAE) was incorporated into PS together with EG. The flame-retardant performances of the resulting composites were evaluated using the limiting oxygen index (LOI), UL-94 vertical burning test, and cone calorimetry test. The strong interaction between EG and PAE provided an effective barrier against heat and oxygen, thereby improving the flame retardancy. The best-performing composite (PA:PEI:EG = 1:1:1 (w/w/w), total flame-retardant loading = 10 parts per 100 parts of PS) exhibited an LOI of 27.7% and a UL-94 V-0 rating. The peak heat release rate (148.8 kW/m²) and total heat release (91.2 MJ/m²) of this composite were lower than those of pure PS by 79.2% and 34.0%, respectively. This study provides guidelines for the production of flame-retardant PS and other polymeric materials. Full article

Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5–17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health. Full article

This study proposes “Prosuming-Parks,” spatial models that integrate industrial activities with green infrastructure to revitalize South Korea’s border regions. A dataset of 2126 brownfields—including aging industrial sites, military facilities, water infrastructure, public buildings, schools, and railways—was compiled and evaluated through a Prosuming-Park Typology Index linking brownfield types with eight industrial sectors. Six models are derived and applied to fifteen municipalities, suggesting tailored strategies for industrial restructuring and ecological restoration. The framework demonstrates how brownfields can seed scalable green networks and, with future inter-Korean cooperation, evolve into transboundary ecological systems. Full article

Background/Objectives: Prostate artery embolization (PAE) has emerged as a relatively new, minimally invasive alternative for the treatment of benign prostatic hyperplasia. We aimed to compare the perioperative outcomes and trends of PAE versus transurethral resection of the prostate (TURP) and laser enucleation. Materials and Methods: We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics, and performed multiple patient-level analyses. Patients with prostate cancer, acute hematuria, and emergent referral to the hospital were excluded. Results: Between 2017 and 2022, a total of 3665 PAEs were performed in Germany compared to 218,388 TURPs and 50,863 laser enucleations. Patients selected for PAE were slightly younger and presented with fewer comorbidities at baseline. The number of laser enucleations increased exponentially in these years, PAEs remained stable, whereas TURPs slightly decreased. Compared to PAE, laser enucleation was associated with higher odds of in-hospital incontinence (4.2% versus 2.7%, OR: 1.6, 95%CI: 1.3–1.9, p < 0.001). On the contrary, PAE was associated with lower odds of in-hospital urinary retention and shorter length of hospital stay compared to TURP (3.2% versus 7.1%, OR: 2.2, 95%CI: 1.8–2.6, p < 0.001, and a 2.6-day difference, 95%CI: 2.5–2.7, p < 0.001, respectively) and laser enucleation (3.2% versus 5%, OR: 1.5, 95%CI: 1.3–1.8, p < 0.001, and a 1.5-day difference, 95%CI: 1.4–1.6, p < 0.001, respectively). Conclusions: PAE offers more favorable perioperative outcomes compared to TURP and laser enucleation, but the use of this relatively new procedure has remained nearly stable in recent years. Full article

Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek^® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics. Full article

This paper presents a W-band high-efficiency and high-output-power power amplifier (PA) based on a 130 nm AlGaN/GaN-on-SiC HEMT process. The PA is designed to deliver optimal output power and gain performance across the entire W-band. A balanced architecture is adopted, combining two amplifier units through Lange couplers. High- and low-impedance microstrip lines are employed for input, output, and inter-stage matching. Each amplifier core adopts a three-stage configuration with gate width ratios of 1:2:4 to enhance gain. The bias network incorporates MIM capacitors and thin-film resistors to improve stability. Measured results indicate a small signal gain exceeding 17 dB under a gate voltage of −2.2 V and a drain voltage of +20 V. Within the 80–86 GHz frequency range, the PA achieves an output power above 34 dBm with a 22 dBm input power, corresponding to a power gain above 12 dB and a power-added efficiency (PAE) greater than 20%. The chip occupies a compact area of 2.65 mm × 3.75 mm. Compared with previously reported works, the proposed PA demonstrates the highest PAE within the 80–86 GHz band. Full article

Introduction: Secure infant/child–caregiver attachment is crucial for the development of social and emotional functioning and can affect long-term outcomes, such as adult relationships, but it may also be influenced by prenatal and early childhood risk factors. Children with a history of prenatal alcohol exposure (PAE) have a complex spectrum of strengths and difficulties and often have the additional risk of early life adversity. There is some evidence that children with PAE are at increased risk of insecure attachment, but it is unclear whether this is consistent or why it is the case. No published review has focused on the relationship between PAE and attachment. Methods: A systematic search of seven academic databases using the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines was undertaken by two reviewers to identify primary studies that have focused on the relationship between PAE and attachment. Quality assessments were undertaken using the Quality of Observational Cohort and Cross-Sectional Studies tool, and the report was written following the PRISMA-ScR checklist. Results: A total of 4199 records were returned from the database searches. A total of 11 studies (eight peer-reviewed papers and three dissertations), published between 1987 and 2021, met the criteria. Five studies showed that PAE was related to insecure or disorganised attachment, two of which showed that infant irritability and caregiver–infant interaction mediated this relationship. The other six studies found no significant relationship between PAE and attachment. Conclusions: This scoping review demonstrates that there is a dearth of published research on this topic, and none that takes advantage of more recent understanding of the relationship between adverse childhood experiences and neurodevelopmental disorders. There is some evidence that PAE may impact the attachment relationship via caregiver–infant interaction and infant irritability, but further studies, including those that assess the additional impact of early life adversity, are needed. Full article

Phthalic acid esters (PAEs), ubiquitously employed as a plasticizer, have been classified as priority environmental pollutants because of their persistence, bioaccumulation, and endocrine-disrupting properties. As a characterized PAE-degrading strain of marine origin, Mycolicibacterium phocaicum RL-HY01 utilizes di-(2-ethylhexyl) phthalate (DEHP) as its sole carbon and energy source. Genome sequencing and RT-qPCR analysis revealed a previously uncharacterized hydrolase gene (dehpH) in strain RL-HY01, which catalyzes ester bond cleavage in PAEs. Subsequently, recombinant expression of the cloned dehpH gene from strain RL-HY01 was established in Escherichia coli BL21(DE3). The purified recombinant DehpH exhibited optimal activity at 30 °C and pH 8.0. Its activity was enhanced by Co²⁺ and tolerant to most metal ions but strongly inhibited by EDTA, SDS, and PMSF. Organic solvents (Tween-80, Triton X-100, methanol, ethanol, isopropanol, acetone, acetonitrile, ethyl acetate, and n-hexane) showed minimal impact. Substrate specificity assay indicated that DehpH could efficiently degrade the short and long side-chain PAEs but failed to hydrolyze the cyclic side-chain PAE (DCHP). The kinetics parameters for the hydrolysis of DEHP were determined under the optimized conditions, and DehpH had a V_max of 0.047 ± 0.002 μmol/L/min, K_m of 462 ± 50 μmol/L, and k_cat of 3.07 s⁻¹. Computational prediction through structural modeling and docking identified the active site, with mutagenesis studies confirming Ser228, Asp324, and His354 as functionally indispensable residues forming the catalytic triad. The identification and characterization of DehpH provided novel insights into the mechanism of DEHP biodegradation and might promote the application of the target enzyme. Full article

Background: Despite advances in prostate cancer treatment, castration-resistant prostate cancer (CRPC) remains clinically challenging due to inherent therapy resistance and a lack of durable alternatives. Although traditional Chinese medicine offers untapped potential, the therapeutic role of paeoniflorin (Pae), a bioactive compound derived from Paeonia lactiflora, in prostate cancer has yet to be investigated. Methods: Using an integrative approach (network pharmacology, molecular docking, and experimental validation), we identified Pae key targets, constructed protein–protein interaction networks, and performed GO/KEGG pathway analyses. A Pae-target-based prognostic model was developed and validated. In vitro and in vivo assays assessed Pae effects on proliferation, migration, invasion, apoptosis, and tumor growth. Results: Pae exhibited potent anti-CRPC activity, inhibiting cell proliferation by 60% and impairing cell migration by 65% compared to controls. Mechanistically, Pae downregulated SRC proto-oncogene, non-receptor tyrosine kinase (SRC) mRNA expression by 68%. The Pae-target-based prognostic model stratified patients into high- and low-risk groups with distinct survival outcomes. Organoid and xenograft studies confirmed Pae-mediated tumor growth inhibition and SRC downregulation. Conclusions: Pae overcomes CRPC resistance by targeting SRC-mediated pathways, presenting a promising therapeutic strategy. Our findings underscore the utility of network pharmacology-guided drug discovery and advocate for further clinical exploration of Pae in precision oncology. Full article

Plastic recycling, especially of polyethylene terephthalate (PET), is essential for reducing plastic waste and promoting sustainability. This study examines the migration of phthalic acid esters (PAEs) from locally sourced recycled PET (rPET) bottles under high-temperature conditions (24 °C, 50 °C, and cyclic 70 °C) over a period of three weeks. High-Performance Liquid Chromatography (HPLC) analysis revealed increased PAE leaching at elevated temperatures, though levels remained below international safety limits. Thermo-Gravimetric Analyzer (TGA) confirmed that plastic caps exhibit higher thermal stability and decompose more completely than plastic bottles under various thermal conditions, highlighting the influence of material composition and thermal aging on degradation behavior. Findings highlight the importance of proper storage and ongoing monitoring to ensure consumer safety. Future research should investigate alternative plasticizers to improve the safety of PET recycling. Full article