Search Results (101)

Background/Objectives: Antibody–drug conjugates are a rapidly evolving class of cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. This review explores experimental and computational advances in ADC design, focusing on structural elements and optimization strategies. Methods: We examined recent developments in the mechanisms of action, antibody engineering, linker chemistries, and payload selection. Emphasis was placed on experimental strategies and computational tools, including molecular modeling and AI-driven structure prediction. Results: ADCs function through both internalization-dependent and -independent mechanisms, enabling targeted drug delivery and bystander effects. The therapeutic efficacy of ADCs depends on key factors: antigen specificity, linker stability, and payload potency. Linkers are categorized as cleavable or non-cleavable, each with distinct advantages. Payloads—mainly tubulin inhibitors and DNA-damaging agents—require extreme potency to be effective. Computational methods have become essential for antibody modeling, developability assessment, and in silico optimization of ADC components, accelerating candidate selection and reducing experimental labor. Conclusions: The integration of experimental and in silico approaches enhances ADC design by improving selectivity, stability, and efficacy. These strategies are critical for advancing next-generation ADCs with broader applicability and improved therapeutic indices. Full article

Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article

Genomic islands (GIs) including integrative and conjugative elements (ICEs), prophages, and integrative plasmids are central drivers of horizontal gene transfer in bacterial plant pathogens. These elements often carry cargo genes encoding virulence factors, antibiotic and metal resistance determinants, and metabolic functions that enhance environmental adaptability. In plant-pathogenic species such as Pseudomonas syringae, GIs contribute to host specificity, immune evasion, and the emergence of novel pathogenic variants. ICEclc and its homologs represent integrative and mobilizable elements whose tightly regulated excision and transfer are driven by a specialized transcriptional cascade, while ICEs in P. syringae highlight the ecological impact of cargo genes on pathogen virulence and fitness. Pathogenicity islands further modulate virulence gene expression in response to in planta stimuli. Beyond P. syringae, GIs in genera such as Erwinia, Pectobacterium, and Ralstonia underpin critical traits like toxin biosynthesis, secretion system acquisition, and topoisomerase-mediated stability. Leveraging high-throughput genomics and structural biology will be essential to dissect GI regulation and develop targeted interventions to curb disease spread. This review synthesizes the current understanding of GIs in plant-pathogenic gammaproteobacteria and outlines future research priorities for translating mechanistic insights into sustainable disease control strategies. Full article

Due to its small size, high transmission ratio and precision, the harmonic reducer is widely used. The design of the flexspline tooth profile is crucial for the transmission accuracy and service life of harmonic reducers. However, the numerous design parameters and the lack of a unified design standard for the flexspline tooth profile make it challenging to accurately determine these parameters. This can lead to issues such as tooth profile interference and excessive stress on the gear teeth during transmission. To address these issues, we propose a novel rapid design framework for the tooth profile of a double-circular-arc common-tangent flexspline in harmonic reducers. Firstly, the mathematical formula for the flexspline tooth profile with a double-circular-arc common-tangent and its conjugate circular spline tooth profile is derived. Then, two-dimensional and three-dimensional parametric finite element models of the harmonic reducer are established, and radial and axial profile modifications of the flexspline are carried out. Based on the parametric two-dimensional finite element model of the harmonic reducer, the optimized Latin hypercube experimental design method is employed to determine the flexspline tooth profile parameters. The method proposed can be implemented using Python language code and integrated into the Abaqus 2019 software, offering the advantage of meeting the requirements for rapid engineering development. Finally, a case study is presented to verify the effectiveness of the proposed design method. Full article

Streptococcus suis is a significant zoonotic pathogen of public health importance. In this study, whole-genome sequencing of 177 isolates of Streptococcus suis, isolated from diseased swine across 15 provinces in China between 2017 and 2019, was performed. A total of 23 serotypes and 28 ST types were identified, with serotypes 2 and 3 comprising 50.8% of the isolates, and sequence types ST353 and ST117 accounting for 23.7%. Clustering analysis based on known virulence-associated factors (VAFs) resulted in the identification of four distinct clusters, and virulence was assessed using animal models, including a unique, highly virulent cluster designated as cluster I. Drug susceptibility testing indicated that 97.7% of the isolates were multidrug-resistant. A total of 26 resistance-associated genes were identified within the genome, 18 of which were associated with integrative and conjugative elements (ICEs) and/or integrative mobilizable elements (IMEs). Nevertheless, our understanding of suis virulence in terms of phylogeny remains incomplete. This study contributes to the understanding of the population structure and genetic characteristics of suis, provides a framework and novel partitioning approach for future investigations into its virulence and pathogenicity, and complements the data on antibiotic resistance. Full article

The global dissemination of plasmid-mediated mcr genes, which confer resistance to the last-resort antibiotic colistin, represents a critical public health challenge driven by the interplay of clinical, agricultural, and environmental factors. This review examines the genetic and ecological dynamics of mcr-bearing plasmids, focusing on their role in disseminating colistin resistance across diverse bacterial hosts and ecosystems. Key plasmid families demonstrate distinct evolutionary strategies, including IncI2, IncHI2, and IncX4. IncI2 plasmids favor stability in livestock and clinical settings. IncHI2 plasmids, on the other hand, leverage transposons to co-select for multidrug resistance, while IncX4 plasmids achieve global dissemination through streamlined, conjugation-efficient architectures. The pervasive spread of mcr genes is exacerbated by their integration into chromosomes via mobile genetic elements and co-selection with resistance to other antibiotic classes, amplifying multidrug-resistant phenotypes. Environmental reservoirs, food chains, and anthropogenic practices further facilitate cross-niche transmission, underscoring the interconnectedness of resistance under the One Health framework. Addressing this crisis requires coordinated strategies, including reducing colistin misuse in agriculture, enhancing surveillance of high-risk plasmid types, and fostering international collaboration to preserve antimicrobial efficacy and mitigate the threat of untreatable infections. Full article

Background: The impact of heat stress on intestinal bacterial antimicrobial resistance (AMR) and its underlying mechanisms is not fully understood. This study aims to explore how heat stress influences AMR in the gut and the mechanisms involved. Methods: A Specific-Pathogen-Free (SPF) mouse model was used, divided into a control group (maintained at 25 °C) and a heat stress group (exposed to 42 °C for 30 min twice daily for 55 days). The effectiveness of the model was verified by RT-qPCR and histopathological analysis. Antibiotic susceptibility testing and clonal analysis (ERIC-PCR) were performed. Colonization assays were conducted to determine the accumulation of resistant strains in the gut. Metagenomic sequencing was conducted to investigated microbial composition. Results: RT-qPCR and Histopathological analysis revealed intestinal damage and significant upregulation of genes related to stress response, intestinal barrier integrity and inflammation, indicating successful model establishment and physiological alterations. Antibiotic susceptibility testing revealed increased resistance to erythromycin, chloramphenicol, and tetracycline among Enterococcus strains. Clonal analysis demonstrated that these resistant strains were clonally unrelated. Sequencing identified a novel ermB-carrying integrative and conjugative element (ICE_FZMF) among four erythromycin-resistant strains. The rectum harbored a higher proportion of erythromycin-resistant Enterococcus strains with elevated minimum inhibitory concentrations (MICs) after 25 days of heat stress exposure. Colonization assays confirmed that heat stress led to the accumulation of erythromycin-resistant Enterococcus in the rectum. Metagenomic sequencing revealed significant changes in microbial composition, favoring anaerobic metabolism. Conclusions: This study suggests that chronic heat stress can promote the emergence of antibiotic-resistant strains through ICE transfer, providing insight for environmental safety. Full article

This article presents a novel, compact, and flexible dual-band magnetoelectric dipole rectenna designed for radio frequency (RF) energy harvesting. The rectenna consists of a unique antenna structure, combining electric and magnetic dipoles to create unidirectional radiation patterns, minimizing interference from the human body. The rectifier is integrated with the antenna through conjugate matching, eliminating the need for additional matching circuits, reducing circuit losses, minimizing design complexity, and improving conversion efficiency. The proposed rectenna utilizes a flexible graphene film as the radiating element, which offers excellent conductivity and corrosion resistance, enabling conformal operation in diverse scenarios. Simulation and experimental results show that the rectenna operates effectively at 3.5 GHz and 4.9 GHz, achieving peak conversion efficiencies of 53.43% and 43.95%, respectively, at an input power of 4 dBm. The simulated and measured results achieved good agreement. The rectenna maintains stable performance under various bending conditions, demonstrating its suitability for flexible, wearable RF energy-harvesting systems. Full article

Proteus mirabilis is a significant foodborne opportunistic pathogen associated with various nosocomial infections. Chicken farms may serve as an important reservoir for P. mirabilis. However, research on antibiotic resistance and genomic features of P. mirabilis in China’s poultry industry is limited. This study isolates P. mirabilis from a breeder farm in China and investigates the dissemination of P. mirabilis and clinically significant antibiotic resistance genes (ARGs), including bla_NDM and bla_CTX-M. From 510 samples, 69 isolates were obtained, classified into 11 sequence types (STs), with ST135 and ST175 predominating. A total of 39 ARGs were detected, including fosA3, floR, bla_CTX-M-3, bla_CTX-M-65, and bla_NDM-1. Genetic analysis revealed that bla_NDM-1 was exclusively located on Salmonella genomic island 1 (SGI1), while bla_CTX-M was found in various mobile genetic elements (MGEs), including Tn7, SXT/R391 integrative conjugative elements (ICEs), Proteus mirabilis genomic resistance island 1 (PmGRI1), and SGI1. Notably, many isolates carried multiple MGEs, suggesting frequent horizontal transfer of ARGs in P. mirabilis. These findings underscore the role of P. mirabilis in carrying and spreading antibiotic resistance, posing significant risks to the poultry industry and public health. Full article

Background/Objectives: Pasteurella multocida commonly colonizes the bovine respiratory tract and can occasionally cause intramammary infections. Here, eight P. multocida isolates from clinical cases of bovine mastitis were investigated for their molecular characteristics as well as phenotypic and genotypic antimicrobial resistance (AMR) properties. Methods: The isolates originated from quarter milk samples obtained in Germany for diagnostic purposes. Antimicrobial susceptibility testing (AST) by broth microdilution was performed according to the Clinical and Laboratory Standards Institute. Closed whole-genome sequences were generated by hybrid assembly of Illumina MiSeq short-reads and Oxford Nanopore MinION long-reads, followed by consecutive sequence analysis. Results: The P. multocida isolates belonged either to capsular:lipopolysaccharide type A:3 (n = 7) or A:6 (n = 1), and multi-locus sequence types 1 (n = 7) or 7 (n = 1). Seven isolates carried AMR genes, such as mef(C), mph(G), strA, strB, aphA1, aadA31, tet(H), tet(Y), floR, catA3, and sul2, as part of an integrative and conjugative element (ICE). These mobile genetic elements, 58,382–78,401 bp in size, were highly similar to the ICEs Tn7406 or Tn7407 that have been previously described in bovine Mannheimia haemolytica and P. multocida, respectively. Moreover, the isolates showed elevated minimal inhibitory concentrations corresponding to the identified AMR determinants. Conclusions: Molecular typing and ICE organization suggest the bovine respiratory tract as reservoir of the investigated mastitis-associated P. multocida. Horizontal cross-genus transfer of multidrug-resistance-mediating ICEs seems to occur under in vivo conditions among different pathogens from cattle in Germany, which underlines the importance of pathogen identification followed by AST for successful bovine mastitis therapy. Full article

Glaesserella parasuis is the etiological agent of Glässer’s disease, which causes high morbidity and mortality in pigs worldwide. Macrolide resistance poses an urgent threat to their treatment, as macrolides are widely used for preventing and treating G. parasuis infections. Here, we determined the susceptibilities to five macrolides and characterized the genetic markers of macrolide resistance. The antimicrobial susceptibility of 117 G. parasuis isolates to erythromycin, tulathromycin, gamithromycin, tylosin, and tilmicosin was evaluated using broth microdilution method. Erythromycin-resistant isolates were sequenced using whole-genome sequencing. Further analysis of these sequences revealed the genetic basis of macrolide resistance in G. parasuis. Our results show that most G. parasuis isolates remained susceptible to the macrolide drugs. For commonly used agents (e.g., tylosin and tilmicosin), elevated minimum inhibitory concentrations (MICs) were observed, whereas for the newer macrolides (e.g., tulathromycin and gamithromycin), the MICs remained almost unchanged. The macrolide resistance gene erm(T) and the A2059G mutation in 23S rRNA were detected in the current study. To the best of our knowledge, integrative and conjugative element (ICE)-borne erm(T) in G. parasuis is reported for the first time in this study. Taken together, these results provide insights into the susceptibility of G. parasuis to macrolides. The presence of erm(T) on ICEs may facilitate its transfer, reducing the effectiveness of macrolide treatment. Full article

Advances in nanotechnology have made it possible to observe and evaluate structures down to the atomic and molecular level. The next step in the development of functional materials is to apply the knowledge of nanotechnology to materials sciences. This is the role of nanoarchitectonics, which is a concept of post-nanotechnology. Nanoarchitectonics is defined as a methodology to create functional materials using nanounits such as atoms, molecules, and nanomaterials as building blocks. Nanoarchitectonics is very general and is not limited to materials or applications, and thus nanoarchitecture is applied in many fields. In particular, in the evolution from nanotechnology to nanoarchitecture, it is useful to consider the contribution of nanoarchitecture in device applications. There may be a solution to the widely recognized problem of integrating top-down and bottom-up approaches in the design of functional systems. With this in mind, this review discusses examples of nanoarchitectonics in developments of advanced devices. Some recent examples are introduced through broadly dividing them into organic molecular nanoarchitectonics and inorganic materials nanoarchitectonics. Examples of organic molecular nanoarchitecture include a variety of control structural elements, such as π-conjugated structures, chemical structures of complex ligands, steric hindrance effects, molecular stacking, isomerization and color changes due to external stimuli, selective control of redox reactions, and doping control of organic semiconductors by electron transfer reactions. Supramolecular chemical processes such as association and intercalation of organic molecules are also important in controlling device properties. The nanoarchitectonics of inorganic materials often allows for control of size, dimension, and shape, and their associated physical properties can also be controlled. In addition, there are specific groups of materials that are suitable for practical use, such as nanoparticles and graphene. Therefore, nanoarchitecture of inorganic materials also has a more practical aspect. Based on these aspects, this review finally considers the future of materials nanoarchitectonics for further advanced devices. Full article

Coating conductive nanoparticles onto the surface of hollow glass microspheres (HGMs) is essential for broadening their applications. However, the low density and high specific surface area of HGM powders, along with the thin walls of the cavity shells and poor surface adhesion, pose challenges for the uniform attachment of functional particles. In this study, we developed a novel integrated process that combines flotation, hydroxylation, and amination pretreatment for HGMs with in situ surface polymerization to achieve a uniform coating of polypyrrole (PPy) on the surface of HGMs. We explored the corresponding growth process and coating mechanism. Our findings indicate that the amount of coating, particle size, and uniformity of PPy on the surface of HGMs are significantly influenced by the pretreatment and the in situ polymerization time, as well as the microspheres/pyrrole feedstock ratio. The in situ polymerization on the surface of HGMs resulted in a uniform encapsulation of spherical PPy, with the average particle size of PPy-coated HGMs (PPy@HGMs) increasing by 14.60% compared to the original HGMs. The elemental nitrogen in the PPy@HGMs primarily exists in the form of C-N and N-H bonds. This study demonstrates that the surface functional groups of HGMs engage in chemical bonding and interactions with PPy molecules. Mechanistic analysis reveals that the hydroxyl and amino groups enriched on the surface of the pretreated HGMs serve as activation centers, facilitating the uniform enrichment of pyrrole monomers and promoting chain growth polymerization of the conjugated chain through nucleophilic and electrophilic interactions with the subamino groups in the pyrrole ring. Additionally, the reaction between the Lewis acid properties of PPy and the Lewis-type electron-donating amino groups in KH550 fosters strong bonding and the formation of a robust interface. Full article

Erysipelas is a significant problem in the waterfowl farming in Poland, and information on the characteristics of the Erysipelothrix rhusiopathiae strains causing this disease is limited. In this study, we determined the serotypes, antimicrobial susceptibility, and potential mechanisms of resistance gene transfer in E. rhusiopathiae isolates (n = 60) from domestic geese and ducks. We also developed a multiplex PCR for the detection of resistance genes. The antimicrobial susceptibility of the isolates was assessed using the broth microdilution method. Resistance genes, integrative conjugative element (ICE)-specific genes, phage-specific genes, and serotype determinants were detected by PCR. Multilocus sequence typing (MLST) was performed for selected resistant strains. The comparative analyses included 260 E. rhusiopathiae strains whose whole genome sequences (WGSs) are publicly available. E. rhusiopathiae isolates represented 7 serotypes, among which serotypes 5 (38.3%) and 1b (28.3%) were the most common. All strains were susceptible to β-lactams, and the vast majority of them were resistant to tetracycline (85%) and enrofloxacin (80%). The percentages of isolates resistant to other antimicrobials used ranged from 3.3% to 16.7%. Ten isolates (16.7%) were found to be multidrug resistant (MDR). The genotypic resistance profiles of the E. rhusiopathiae strains corresponded to their phenotypic resistance, and the amplification patterns obtained using the 10-plex PCR developed in this study were fully consistent with the results of single PCRs. The most prevalent resistance gene was tetM. In enrofloxacin-resistant strains, nonsynonymous mutations in the gyrA and parC genes were identified. The presence of ICE-specific genes was confirmed in resistant strains, and in MDR isolates of serotype 8 that represented sequence type (ST) 113, prophage DNA (Javan630-like) linked to the lsaE gene was additionally detected. The results indicate that β-lactam antibiotics should be the first choice for the treatment of waterfowl erysipelas in Poland. ICEs, including a transposon from the Tn916/Tn1545 family, and bacteriophages are most likely responsible for the transfer of resistance genes in E. rhusiopathiae. Full article

Corynebacterium striatum, present in the microbiota of human skin and nasal mucosa, has recently emerged as a causative agent of hospital-acquired infections, notable for its resistance to multiple antimicrobials. Its mobilome comprises several mobile genetic elements, such as plasmids, transposons, insertion sequences and integrons, which contribute to the acquisition of antimicrobial resistance genes. This study analyzes the contribution of the C. striatum mobilome in the transfer and dissemination of resistance genes. In addition, integrative and conjugative elements (ICEs), essential in the dissemination of resistance genes between bacterial populations, whose role in C. striatum has not yet been studied, are examined. This study examined 365 C. striatum genomes obtained from the NCBI Pathogen Detection database. Phylogenetic and pangenome analyses were performed, the resistance profile of the bacterium was recognized, and mobile elements, including putative ICE, were detected. Bioinformatic analyses identified 20 antimicrobial resistance genes in this species, with the Ermx gene being the most predominant. Resistance genes were mainly associated with plasmid sequence regions and class 1 integrons. Although an ICE was detected, no resistance genes linked to this element were found. This study provided valuable information on the geographic spread and prevalence of outbreaks observed through phylogenetic and pangenome analyses, along with identifying antimicrobial resistance genes and mobile genetic elements that carry many of the resistance genes and may be the subject of future research and therapeutic approaches. Full article