Precise Mode Research Articles

Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration

The neurotoxicant trimethyltin (TMT) triggers cognitive impairment and hippocampal neurodegeneration. TMT is a useful research tool for the study of Alzheimer's disease (AD) pathogenesis and treatment. Although the antidiabetic agent metformin has shown promising neuroprotective effects, however, its precise modes of action in neurodegenerative disorders need to be further elucidated. In this study, we investigated whether metformin can mitigate TMT cognition impairment and hippocampal neurodegeneration. To induce an AD-like phenotype, TMT was injected i.p. (8 mg/kg) and metformin was administered daily p.o. for 3 weeks at 200 mg/kg. Our results showed that metformin administration to the TMT group mitigated learning and memory impairment in Barnes maze, novel object recognition (NOR) task, and Y maze, attenuated hippocampal oxidative, inflammatory, and cell death/pyroptotic factors, and also reversed neurodegeneration-related proteins such as presenilin 1 and p-Tau. Hippocampal level of AMP-activated protein kinase (AMPK) as a key regulator of energy homeostasis was also improved following metformin treatment. Additionally, metformin reduced hippocampal acetylcholinesterase (AChE) activity, glial fibrillary acidic protein (GFAP)-positive reactivity, and prevented the loss of CA1 pyramidal neurons. This study showed that metformin mitigated TMT-induced neurodegeneration and this may pave the way to develop new therapeutics to combat against cognitive deficits under neurotoxic conditions.

Head Space GC-MS/MS Method for Quantification of Five Nitrosoamine-Genotoxic Impurities in Metformin HCl

Background: N-nitrosamines have recently been discovered in metformin hydrochloride and other generic drugs. To quantify the five N-nitrosamines in metformin hydrochloride, we devised sensitive and reliable multiple reactions monitoring mode-based GCMS/ MS technique, particularly, N-nitrosodiethy amine (NDEA), N-nitroso ethyl isopropylamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodipropylamine (NDPA), as well as N-nitrosodibutylamine (NDBA). Objective: To develop a sensitive, precise, and accurate MRM mode based GC-MS/MS method for the quantification of five N-nitrosamines in metformin hydrochloride and valídate as per ICH guidelines. Methods: The settings for mass spectrometry and gas chromatography were optimized. With the linearity, sensitivity, specificity, accuracy, and precision of the parameter, the procedure was as per the recommendation of ICH: International Council for Harmonization guidelines. Results: N-nitrosamines in metformin hydrochloride had detection and quantification limits of 0.001 ppm and 0.004 ppm, correspondingly. The obtained results were within the sensitivity limitations issued by the US Food and Drug Administration. The calibration curve's regression coefficients for five N-nitrosamines were over 0.99, demonstrating the process's good linearity. The retrievals of N-nitrosamines in metformin hydrochloride between 97.1 – 127.4 %. The RSD (Relative Standard Deviation) was lower than 10 % for both inter-day and intra-day precision studies. Conclusion: The proposed method exhibited a rapid analysis capability, high accuracy, sensitivity, and precision, making it a trustworthy method for monitoring N-nitrosamines in metformin hydrochloride.

Computational modeling to understand the interaction of TMPyP4 with a G-quadruplex

The potential of small molecules to bind to G-quadruplex-forming sequences in oncogene promoter regions, thereby regulating their structural equilibrium, has been explored as a promising strategy for cancer chemotherapy. The model drug 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine (TMPyP4) has been shown to have an affinity toward G-quadruplex DNA. However, the precise sites and modes of TMPyP4 binding to G-quadruplex DNA remain a subject of debate. In this study, we focus on identifying potential binding sites on a mutant c-MYC sequence known to fold into a single 1:2:1 loop isomer quadruplex. Our findings provide insights into the 4:1 stoichiometry reported for TMPyP4 binding to this G-quadruplex. Binding enthalpy and free energy calculations show that intercalation of a TMPyP4 molecule between the quadruplexes is thermodynamically favorable. Our calculations suggest that two of the binding sites are located at the top and bottom of the quadruplex, respectively, while the remaining two are likely intercalations.

Targeting PilA in Acinetobacter baumannii: A Computational Approach for Anti-Virulent Compound Discovery.

Acinetobacter baumannii (A. baumannii) has emerged as a critical global pathogen due to its ability to acquire resistance traits. This bacterium exhibits two distinct forms of motility: twitching, mediated by type IV pili (T4P), and surface-associated motility, independent of appendages. T4P is crucial in various bacterial species, facilitating twitching motility, biofilm formation, and host-cell adhesion. The synthesis of T4P is a common feature among Gram-negative pathogens, particularly A. baumannii, suggesting that PilA could be a viable target for biofilm-related treatments. This study aims to develop drug molecules to mitigate A. baumannii virulence by targeting PilA. Using Schrodinger software, we screened 60,766 compounds from the CMNPD, ChemDiv, and Enamine antibacterial databases through high-throughput virtual screening. The top two compounds from each database, identified through extra precision (XP) mode, were subjected to further studies. Among the six compounds identified (CMNPD18469, CMNPD20698, Z2377302405, Z2378175729, N039-0021, and N098-0051), docking scores ranged from -5.0 to -7.5kcal/mol. Subsequently, we conducted 300ns molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis of the PilA-ligand complexes. Analysis of the simulation trajectories indicated structural stability and consistent behavior of the PilA-ligand complexes in a dynamic environment. Notably, the PilA-N098-0051 complex exhibited enhanced stability and robust binding interactions, underscoring its potential as a therapeutic agent. These findings suggest that the identified compounds, particularly N098-0051, hold promise as potent molecules targeting PilA, necessitating further validation through in vitro and in vivo studies.

Enhanced stochastic coding framework for discriminating faults and cyber incidents in hybrid systems

AbstractThis article presents an innovative approach for distinguishing replay attacks from faults in hybrid systems. To develop the idea at first, a novel technique for replay attack detection, which differentiates it from typical system faults, is introduced. This is achieved through a tactical combination of stochastic coding and a window‐based comparison mechanism, setting a new standard in hybrid system security. In the realm of fault detection, robust L2‐L∞ adaptive observers are employed for precise mode detection, allowing for an accurate assessment of the system's operational state. Additionally, robust H∞ Sliding Mode Observers are utilized to identify abnormal behaviours in the system's output, further solidifying the fault detection capabilities. A significant enhancement in the proposed approach is the integration of a Luenberger observer with the Butterworth low‐pass filter. This novel addition not only refines the filtering process but also contributes to the overall reliability and accuracy of the system. The efficiency and versatility of these methods are demonstrated through their application to a four‐tank hybrid system. This practical simulation showcases the adaptability of the approach to real‐world scenarios, highlighting its potential in diverse applications within the field of hybrid systems.

In silico analysis of the melamine structural analogues interaction with calcium-sensing receptor: A potential for nephrotoxicity

In recent years, melamine, and its structural analogues, as adulterants in various food products including protein supplements,have been widely studied for their nephrotoxic effects. Previous research has presented evidence that certain small molecules can alter the calcium-sensing receptor (CaSR) function, contributing to nephrotoxicity. Melamine, for example, has been observed in in vitro settings to interact with the allosteric binding site of CaSR, resulting in uncontrolled CaSR activation. This activation results in the production of reactive oxygen species, which eventually causes kidney cell apoptosis and/or necrosis. The present research used the in silico molecular modelling to evaluate the CaSR binding profilesof four common adulterants in protein supplements: melamine, cyanuric acid, uric acid, and melamine cyanurate. Using Schrödinger’s Maestro docking software (version 13.2.128), the docking studies coupled a noncovalent extra precision mode with the molecular mechanics-generalized born surface area (MM-GBSA) simulation for enhanced binding affinity prediction accuracy. This study identified that cyanuric acid, uric acid, and melamine cyanurate have greater CaSR binding affinities than melamine. Interestingly, melamine cyanurate had the highest binding potential to CaSR. Previous animal studies have reported high concentrations of melamine cyanurate complex in rat kidneys following melamine administration. These findings demonstrate a molecular explanation melamine cyanurate complex-induced nephrotoxicity. This research offers new insight regarding the probable mechanism through which melamine, its analogues, and complexes may cause nephrotoxicity.

Discovery of CZL-046 with an (S)-3-Fluoropyrrolidin-2-one Scaffold as a p300 Bromodomain Inhibitor for the Treatment of Multiple Myeloma.

E1A binding protein (p300) is a promising therapeutic target for the treatment of cancer. Herein, we report the discovery of a series of novel inhibitors with an (S)-3-fluoropyrrolidin-2-one scaffold targeting p300 bromodomain. The best compound 29 (CZL-046) shows potent inhibitory activity of p300 bromodomain (IC50 = 3.3 nM) and antiproliferative activity in the multiple myeloma (MM) cell line (OPM-2 IC50 = 51.5 nM). 29 suppressed the mRNA levels of c-Myc and IRF4 and downregulated the expression of c-Myc and H3K27Ac. Compared to the lead compound 5, 29 exhibits significantly improved in vitro and in vivo metabolic properties. Oral administration of 29 with 30 mg/kg achieved a TGI value of 44% in the OPM-2 xenograft model, accompanied by good tolerability. The cocrystal structure of CREB binding protein bromodomain with 29 provides an insight into the precise binding mode. The results demonstrate that 29 is a promising p300 bromodomain inhibitor for the treatment of MM.

Alpha-1-B glycoprotein (A1BG) inhibits sterol-binding and export by CRISP2

Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in various processes, including sperm maturation and cancer progression. They are mostly secreted glycoproteins and share a unique conserved CAP domain. The precise mode of action of these proteins, however, has remained elusive. Saccharomyces cerevisiae expresses three members of this protein family, which bind sterols in vitro and promote sterol secretion from cells. This sterol-binding and export function of yeast Pry proteins is conserved in the mammalian CRISP proteins and other CAP superfamily members. CRISP3 is an abundant protein of the human seminal plasma and interacts with alpha-1-B glycoprotein (A1BG), a human plasma glycoprotein that is upregulated in different types of cancers. Here we examined whether the interaction between CRISP proteins and A1BG affects the sterol-binding function of CAP family members. Co-expression of A1BG with CAP proteins abolished their sterol export function in yeast and their interaction inhibits sterol-binding in vitro. We map the interaction between A1BG and CRISP2 to the third of five repeated immunoglobulin-like (Ig) domains within A1BG. Interestingly, the interaction between A1BG and CRISP2 requires magnesium, suggesting that coordination of Mg2+ by the highly conserved tetrad residues within the CAP domain is essential for a stable interaction between the two proteins. The observation that A1BG modulates the sterol-binding function of CRISP2, has potential implications for the role of A1BG and related Ig domain containing proteins in cancer progression and the toxicity of reptile venoms containing CRISP proteins.

The Potential of Chat-Based Artificial Intelligence Models in Differentiating Between Keloid and Hypertrophic Scars: A Pilot Study.

Lasting scars such as keloids and hypertrophic scars adversely affect a patient's quality of life. However, these scars are frequently underdiagnosed because of the complexity of the current diagnostic criteria and classification systems. This study aimed to explore the application of Large Language Models (LLMs) such as ChatGPT in diagnosing scar conditions and to propose a more accessible and straightforward diagnostic approach. In this study, five artificial intelligence (AI) chatbots, including ChatGPT-4 (GPT-4), Bing Chat (Precise, Balanced, and Creative modes), and Bard, were evaluated for their ability to interpret clinical scar images using a standardized set of prompts. Thirty mock images of various scar types were analyzed, and each chatbot was queried five times to assess the diagnostic accuracy. GPT-4 had a significantly higher accuracy rate in diagnosing scars than Bing Chat. The overall accuracy rates of GPT-4 and Bing Chat were 36.0% and 22.0%, respectively (P = 0.027), with GPT-4 showing better performance in terms of specificity for keloids (0.6 vs. 0.006) and hypertrophic scars (0.72 vs. 0.0) than Bing Chat. Although currently available LLMs show potential for use in scar diagnostics, the current technology is still under development and is not yet sufficient for clinical application standards, highlighting the need for further advancements in AI for more accurate medical diagnostics. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online instructions to authors www.springer.com/00266 .

Plasmodium SEY1 is a novel druggable target that contributes to imidazolopiperazine mechanism of action.

The precise mode of action of ganaplacide (KAF156), a phase III antimalarial candidate, remains elusive. Here we employ omics-based methods with the closely related chemical analog, GNF179, to search for potential Plasmodium targets. Ranking potential targets derived from chemical genetics and proteomic affinity chromatography methodologies identifies SEY1, or Synthetic Enhancement of YOP1, which is predicted to encode an essential dynamin-like GTPase implicated in homotypic fusion of endoplasmic reticulum (ER) membranes. We demonstrate that GNF179 decreases Plasmodium SEY1 melting temperature. We further show that GNF179 binds to recombinant Plasmodium SEY1 and subsequently inhibits its GTPase activity, which is required for maintaining ER architecture. Using ultrastructure expansion microscopy, we find GNF179 treatment changes parasite ER and Golgi morphology. We also confirm that SEY1 is an essential gene in P. falciparum. These data suggest that SEY1 may contribute to the mechanism of action of imidazolopiperazines and is a new and attractive druggable target.

MicroMagnetic.jl: A Julia package for micromagnetic and atomistic simulations with GPU support

Abstract MicroMagnetic.jl is an open-source Julia package for micromagnetic and atomistic simulations. Using the features of the Julia programming language, MicroMagnetic.jl supports CPU and various GPU platforms, including NVIDIA, AMD, Intel, and Apple GPUs. Moreover, MicroMagnetic.jl supports Monte Carlo simulations for atomistic models and implements the nudged-elastic-band method for energy barrier computations. With built-in support for double and single precision modes and a design allowing easy extensibility to add new features, MicroMagnetic.jl provides a versatile toolset for researchers in micromagnetics and atomistic simulations.

Discovery of 4-Hydroxyphenylpyruvate dioxygenase inhibitors with novel pharmacophores

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is pivotal in tyrosine metabolism and essential for plant survival. Its inhibition leads to leaf bleaching and plant death. While current HPPD inhibitors are effective, they pose phytotoxicity risks and may contribute to herbicide resistance. Here, we investigated the inhibitory potential of sethoxydim and atovaquone, which traditionally target acetyl-CoA carboxylase and the cytochrome bc1 complex, respectively. Both atovaquone and the degradation product of sethoxydim exhibited moderate HPPD inhibitory activity. But the mechanism by which sethoxydim inhibited HPPD remained unclear. Therefore, we embarked on an investigation into the crystal structure of the complex, with the aim of elucidating its precise binding mode. Our findings revealed that sethoxydim degrades in solution, producing dealkoxy sethoxydim as the active component in HPPD inhibition. Structural analysis elucidated the binding modes of atovaquone and dealkoxy sethoxydim with HPPD. These binding motifs represent novel pharmacophores and offer promising leads for developing HPPD inhibitors with improved pesticidal profiles.

Engineering ideal helical topological networks in stanene via Zn decoration

The xene family of topological insulators plays a key role in many proposals for topological electronic, spintronic, and valleytronic devices. These proposals rely on applying local perturbations, including electric fields and proximity magnetism, to induce topological phase transitions in xenes. However, these techniques lack control over the geometry of interfaces between topological regions, a critical aspect of engineering topological devices. We propose adatom decoration as a method for engineering atomically precise topological edge modes in xenes. Our first-principles calculations show that decorating stanene with Zn adatoms exclusively on one of two sublattices induces a topological phase transition from the quantum spin Hall (QSH) to quantum valley Hall (QVH) phase and confirm the existence of spin-valley polarized edge modes propagating at QSH/QVH interfaces. We conclude by discussing technological applications of these edge modes that are enabled by the atomic precision afforded by recent advances in adatom manipulation technology.

Crystal structure of NYN domain of Human KHNYN in complex with single strand RNA

KHNYN protein with a KH-like domain and a NYN endoribonuclease domain interacts with Zinc-finger antiviral protein (ZAP). ZAP isoforms recognize viral or cellular RNAs and recruit KHNYN to form the ZAP: KHNYN complex. Although the structures of several PIN/NYN domains have been determined, the precise substrate RNA binding mode remains poorly understood. This study presents the crystal structure of a complex of the NYN domain of KHNYN and a 7mer RNA from interferon lambda3 (IFNL3). Our structural analysis reveals that NYN domain of human KHNYN shares structural similarities with other NYN domains of ZC3H12Ã C proteins. The RNA is bound in the central groove region of the protein, facilitated by interactions including coordination by two Mg2+ ions, hydrophobic interactions, and hydrogen bonds. In the observed RNA-protein complex, the U5, A6, and U7 bases are stacked on top of one another, while U3 and U4 bases adopt an “open” conformation (as opposed to base-stacked), forming a U-shaped overall structure. Mutagenesis studies underscore the significance of residues involved in RNA binding for RNase activity. Interestingly, NYN domain of human KHNYN forms a head-to-tail dimer in the crystal, a structural feature also observed in other homologous PIN/NYN proteins, with a residue from the symmetry mate contributing to hydrophobic interactions with the bound RNA.

A multi-scale attributes fusion model for travel mode identification using GPS trajectories

ABSTRACT Travel mode recognition is a key issue in urban planning and transportation research. While traditional travel surveys use manual data collection and have limited coverage, poor timeliness, and insufficient sample capacity, recent advancements in Global Positioning System (GPS) technology allow large-scale data collection and offer novel opportunities to enhance travel mode recognition. However, existing studies often neglect regular differences and changes in motion states across different travel modes and fail to fully integrate multi-scale spatio-temporal features, which limits the accurate classification of travel modes. To fill this gap, this study proposes a multi-scale spatio-temporal attribute fusion (MSAF) model for precise travel mode identification using solely GPS trajectories without altering their sampling rate. The MSAF model segments GPS trajectories into various temporal and spatial scales, extracting local motion states and spatial features at multiple scales. The spatio-temporal feature extraction module is constructed to extract local motion states and capture spatio-temporal dependencies. Additionally, the model incorporates a multi-scale feature fusion module, which effectively combines features of various scales through a series of fusion techniques to obtain a comprehensive representation, enabling automatic and accurate travel mode identification. Experiments on real-world datasets, including the GeoLife Trajectories dataset and the Sussex-Huawei Locomotion-Transportation (SHL) dataset, demonstrate the effectiveness of the MSAF model, achieving a competitive accuracy of 95.16% and 91.70%. This represents an improvement of 2.50% to 7.95% and 0.8% to 6.62% over several state-of-the-art baselines, effectively addressing sample imbalance challenges. Moreover, the experiments demonstrate the significant role of multiscale feature fusion in improving model performance.

Practical Research on the Comprehensive Quality of School-Enterprise Joint Precision Training of Higher Vocational Pharmacy Professionals

With the deepening of China's higher vocational education reform, the innovation of talent training mode has become the key to improve the quality of education and adapt to the needs of society. Especially in the field of pharmacy, the comprehensive requirements for the quality of professional and technical personnel are increasing day by day. Centering on the precise training mode of school-enterprise cooperation, this paper conducts practical research on the comprehensive quality training of pharmacy professionals in higher vocational colleges, aiming to explore and optimize the talent training program, in order to better adapt to the diversified needs of the development of enterprises in the industry. The research adopts the method of combining quantitative data analysis with qualitative research, and many representative pharmaceutical enterprises were selected to carry out research together with five higher vocational colleges in the province. Through in-depth interviews with 100 students and 40 corporate instructors, as well as tracking the student internship and project cooperation process, multi-dimensional data including internship effectiveness, skill mastery level, job adaptability and innovative thinking ability were collected. The research results show that the precise training mode of school-enterprise cooperation has significantly improved students' professional skills and practical ability, and the employment rate of students has increased by 15% compared with the traditional mode. However, the survey also found that this model is insufficient in terms of students' independent learning ability and the depth of theoretical knowledge. To this end, the research puts forward targeted improvement measures, such as increasing case teaching, simulation experiment and enterprise internal training, to strengthen students' self-study ability and innovative thinking. The conclusions and suggestions of this study provide a reference for the school-enterprise cooperation mode in other professional fields, and have certain guiding significance and practical value for the development of local higher vocational education.

Molecular insight into the neutralization mechanism of human-origin monoclonal antibody AH100 against Hantaan virus.

Both Old World and New World hantaviruses are transmitted through rodents and can lead to hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome in humans without the availability of specific therapeutics. The square-shaped surface spikes of hantaviruses consist of four Gn-Gc heterodimers that are pivotal for viral entry into host cells and serve as targets for the immune system. Previously, a human-derived neutralizing monoclonal antibody, AH100, demonstrated specific neutralization against the Old World hantavirus, Hantaan virus. However, the precise mode binding of this neutralizing monoclonal antibody remains unclear. In the present study, we determined the structure of the Hantaan virus Gn-AH100 antigen-binding fragment complex and identified its epitope. Crystallography revealed that AH100 targeted the epitopes on domain A and b-ribbon and E3-like domain. Epitope mapping onto a model of the higher order (Gn-Gc)4 spike revealed its localization between neighboring Gn protomers, distinguishing this epitope as a unique site compared to the previously reported monoclonal antibodies. This study provides crucial insights into the structural basis of hantavirus neutralizing antibody epitopes, thereby facilitating the development of therapeutic antibodies.IMPORTANCEHantaan virus (HTNV) poses a significant threat to humans by causing hemorrhagic fever with renal syndrome with high mortality rates. In the absence of FDA-approved drugs or vaccines, it is urgent to develop specific therapeutics. Here, we elucidated the epitope of a human-derived neutralizing antibody, AH100, by determining the HTNV glycoprotein Gn-AH100 antigen-binding fragment (Fab) complex structure. Our findings revealed that the epitopes situated on the domain A and b-ribbon and E3-like domain of the HTNV Gn head. By modeling the complex structure in the viral lattice, we propose that AH100 neutralizes the virus by impeding conformational changes of Gn protomer, which is crucial for viral entry. Additionally, sequence analysis of all reported natural isolates indicated the absence of mutations in epitope residues, suggesting the potential neutralization ability of AH100 in diverse isolates. Therefore, our results provide novel insights into the epitope and the molecular basis of AH100 neutralization.

The Role of Probiotics in Skin Care: Advances, Challenges, and Future Needs.

The skin, being the largest organ in the human body, plays a pivotal role in safeguarding the body against invasive pathogens. Therefore, it is essential to reinforce and protect this vital organ. Current research supports the impact of probiotics on skin health and their ability to alleviate various skin disorders. However, the effectiveness and probable side effects of probiotics in skin care remain a subject of debate, necessitating further investigation and analysis. Hence, this study aims to highlight existing gaps and future needs in the current research on probiotics in skin care and pave the way for future investigations. Therefore, we scrutinized the effects of oral (fermented foods and dietary supplements) and non-oral/topical probiotics on skin care, and the mechanism of probiotics that affect skin health. The results of most studies showed that fermented foods containing probiotics, particularly dairy products, positively impact skin health. The research results regarding the efficacy of probiotic supplements and live strains in treating skin disorders show promising potential. However, safety evaluations are crucial, to identify any potential adverse effects. While research has identified numerous potential mechanisms by which probiotics may influence skin health, a complete understanding of their precise mode of action remains elusive. However, it seems that probiotics can exert their positive effects through the gut-skin and gut-skin-brain axis on the human body. Therefore, following the identification of safe probiotics, additional studies should be carried out to establish optimal dosages, potential side effects, suitable regulatory guidelines, and validation methods.

Coatings Based on Essential Oils for Combating Antibiotic Resistance.

In the current era of widespread antimicrobial resistance, the utilization of essential oils (EOs) derived from plants has emerged as a promising alternative in combating pathogens that have developed resistance to antibiotics. This review explores the therapeutic potential of essential oils as valuable tools in restoring the efficacy of antibiotics, highlighting their unique ability to affect bacteria in multiple ways and target various cellular systems. Despite the challenge of elucidating their precise mode of action, EOs have shown remarkable results in rigorous testing against a diverse range of bacteria. This review explores the multifaceted role of EOs in combating bacterial microorganisms, emphasizing their extraction methods, mechanisms of action, and comparative efficacy against synthetic antibiotics. Key findings underscore the unique strategies EOs deploy to counter bacteria, highlighting significant differences from conventional antibiotics. The review extends to advanced coating solutions for medical devices, exploring the integration of EO formulations into these coatings. Challenges in developing effective EO coatings are addressed, along with various innovative approaches for their implementation. An evaluation of these EO coatings reveals their potential as formidable alternatives to traditional antibacterial agents in medical device applications. This renaissance in exploring natural remedies emphasizes the need to combine traditional wisdom with modern scientific advancements to address the urgent need for effective antimicrobial solutions in the post-antibiotic era.

Precise mode control of laser-written waveguides for broadband, low-dispersion 3D integrated optics

Three-dimensional (3D) glass chips are promising waveguide platforms for building hybrid 3D photonic circuits due to their 3D topological capabilities, large transparent windows, and low coupling dispersion. At present, the key challenge in scaling down a benchtop optical system to a glass chip is the lack of precise methods for controlling the mode field and optical coupling of 3D waveguide circuits. Here, we propose an overlap-controlled multi-scan (OCMS) method based on laser-direct lithography that allows customizing the refractive index profile of 3D waveguides with high spatial precision in a variety of glasses. On the basis of this method, we achieve variable mode-field distribution, robust and broadband coupling, and thereby demonstrate dispersionless LP21-mode conversion of supercontinuum pulses with the largest deviation of <0.1 dB in coupling ratios on 210 nm broadband. This approach provides a route to achieve ultra-broadband and low-dispersion coupling in 3D photonic circuits, with overwhelming advantages over conventional planar waveguide-optic platforms for on-chip transmission and manipulation of ultrashort laser pulses and broadband supercontinuum.