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The main aim of this work is to account for the prevention and control of microbial growth on surfaces of interest in medical technology. Surface modification is often achieved by physiotherapy or chemical treatments that can involve time-consuming steps, hazardous reagents, and harsh conditions. One of the ways to overcome these drawbacks is the use of surface-active proteins such as hydrophobins. They can form stable protein layers on different surfaces, serving as anchoring points for other molecules of interest. The fungal hydrophobin Vmh2, already exploited for its adhesive ability, has been fused with the antimicrobial peptide GKY20, forming the chimeric protein used herein for functionalizing polystyrene (PS) and bacterial cellulose (BC). As a natural biomass, BC has multiple advantages, including biodegradability, low cost, renewability, high purity, and excellent mechanical properties. The chimeric protein has been proven to successfully adhere to both surfaces. A strong decrease in biofilm formation on PS and a good bactericidal effect of BC have been demonstrated. These findings provide evidence of an alternative strategy to obtain functional composites using a green, easy process.

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Water is essential to all life on earth. It is a major component that makes up living organisms and plays a vital role in multiple biological processes. It provides a medium for chemical and enzymatic reactions in the cell and is a major player in osmoregulation and the maintenance of cell turgidity. Despite this, many organisms, called anhydrobiotes, are capable of surviving under extremely dehydrated conditions. Less is known about how anhydrobiotes adapt and survive under desiccation stress. Studies have shown that morphological and physiological changes occur in anhydrobiotes in response to desiccation stress. Certain disaccharides and proteins, including heat shock proteins, intrinsically disordered proteins, and hydrophilins, play important roles in the desiccation tolerance of anhydrobiotes. In this review, we summarize the recent findings of desiccation tolerance in the budding yeast Saccharomyces cerevisiae. We also propose that the yeast under desiccation could be used as a model to study neurodegenerative disorders.

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Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

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As we know, valley-Hall kink states or pseudospin helical edge states are excited by polarized-momentum-locking [left-handed circular polarization (LCP) and right-handed circular polarization (RCP)] because the valley-Hall kink modes or pseudospin polarized modes have intrinsic and local chirality, which is difficult for these states to achieve phase modulation. Here we theoretically design and study a compatible topological photonic system with coexistence of photonic quantum Hall phase and pseudospin Hall phase, which is composed of gyromagnetic photonic crystals with a deformed honeycomb lattice containing six cylinders. A typical kind of hybrid topological waveguide states with pseudospin-characteristic, magnetic field-dependent, and strong robustness against backscattering and perfect electric conductor (PEC) is realized in the present system. Furthermore, we re-design a structure with intersection-liked, achieve splitting for one-way pseudospin quantum Hall edge states by using phase modulation. Robustness of the one-way pseudospin-quantum Hall edge states in splitting has been demonstrated as well. Additionally, PEC inserted in transport channel brings optical path difference in waveguide transmission, which would influence splitting for hybrid topological waveguide states in phase difference modulation. This work not only provides a new way for manipulation (i.e., phase modulation) of hybrid topological waveguide states in compatible topological photonic system from distinct topological classes but also has potential in various applications, such as sensing, signal processing, and on-chip communications.

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With the increased occurrence of bacteria resistance to conventional antibiotics, the development of novel antimicrobials is urgently needed. Traditional biomaterials used for delivering these agents often struggle to achieve sustained release while maintaining non-cytotoxic properties. In this study, we present an innovative approach using bacterial polyhydroxyalkanoates (PHA) as a carrier for antimicrobial delivery, specifically designed for wound healing applications. Octenidine dihydrochloride (OCT), a widely used antimicrobial agent, served as our model drug. To achieve the desired balance of OCT release and low cytotoxicity, we introduced a novel bio-derived additive, 3-hydroxy-pentadecanoic acid (3OHC15), extracted from bacteria. This additive significantly improved the hydrophilicity of PHA films, resulting in enhanced and sustained release of OCT. Importantly, the additive did not adversely affect the material's tensile strength or thermal properties. The increased OCT release led to improved antibacterial activity against both Gram-negative and -positive strains. Most notably, the incorporation of 3OHC15 in PHA mitigated the cytotoxic effects of the released drug on human fibroblasts, ensuring biocompatibility. This work represents a novel strategy in the design of biomaterials for the delivery of bioactive compounds, achieving a critical balance between efficacy and cytocompatibility, and marks a significant advancement in the field of antimicrobial delivery systems.

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Wound infections pose a significant challenge in healthcare, and traditional antibiotic treatments often result in the development of resistant pathogens. Addressing this gap, ProGel is introduced, a living hydrogel created by entrapping probiotic Lactobacillus plantarum as a therapeutic component within a gelatin matrix. With a double-syringe system, ProGel can be easily mixed and applied, conforming swiftly to any wound shape and forming hydrogel in situ. It also demonstrates robust mechanical and self-healing properties owing to the Schiff-base bonds. ProGel sustains more than 80% viability of the entrapped L. plantarum while restricting their escape from the hydrogel. After a week of storage, more than 70% viability of the entrapped L. plantarum is preserved. Importantly, ProGel exhibits broad-spectrum antimicrobial efficacy against pathogens commonly associated with wound infections, i.e., Pseudomonas aeruginosa (7Log reduction), Staphylococcus aureus (3-7Log reduction), and Candida albicans (40-70% reduction). Moreover, its cytocompatibility is affirmed through coculture with human dermal fibroblasts. The effectiveness of ProGel is further highlighted in more clinically relevant tests on human skin wound models infected with P. aeruginosa and S. aureus, where it successfully prevents the biofilm formation of these pathogens. This study showcases an injectable living hydrogel system for the management of complex wound infections.

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Professional tooth whitening in the dental office is a popular cosmetic procedure and is performed under carefully monitored conditions. This allows the controlled application of a relatively high concentration of bleaching ingredients based on hydrogen peroxide or peroxide derivatives which produce reactive oxygen species, and consequently induce enamel erosion, alteration of the microhardness of the teeth, irritation of the gums, pain or post bleach sensitivity. This short communication describes the successful and reliable application of a new professional tooth whitening technique using a novel phthalimido peroxycaproic acid complex while avoiding reactive oxygen species.

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Osteoarthritis (OA) is a disease of the joints, characterized by chronic inflammation, cartilage destruction and extracellular matrix (ECM) remodeling. Aberrant chondrocyte hypertrophy promotes cartilage destruction and OA development. Collagen X, the biomarker of chondrocyte hypertrophy, is upregulated by runt-related transcription factor 2 (Runx2), which is mediated by the bone morphogenetic protein 4 (BMP4)/Smad1 signaling pathway. BMP binding endothelial regulator (BMPER), a secreted glycoprotein, acts as an agonist of BMP4. 5,7,3',4'-tetramethoxyflavone (TMF) is a natural flavonoid derived from Murraya exotica L. Results of our previous study demonstrated that TMF exhibits chondroprotective effects against OA development through the activation of Forkhead box protein O3a (FOXO3a) expression. However, whether TMF suppresses chondrocyte hypertrophy through activation of FOXO3a expression and inhibition of BMPER/BMP4/Smad1 signaling remains unknown. Results of the present study revealed that TMF inhibited collagen X and Runx2 expression, inhibited BMPER/BMP4/Smad1 signaling, and activated FOXO3a expression; thus, protecting against chondrocyte hypertrophy and OA development. However, BMPER overexpression and FOXO3a knockdown impacted the protective effects of TMF. Thus, TMF inhibited chondrocyte hypertrophy in OA cartilage through mediating the FOXO3a/BMPER signaling pathway.

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Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.

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Oral squamous cell carcinoma (OSCC) is the most common malignant cancer of the head and neck, with high morbidity and mortality, ranking as the sixth most common cancer in the world. The treatment of OSCC is mainly radiotherapy, chemotherapy and surgery, however, the prognosis of patients is still poor and the recurrence rate is high. This paper reviews the range of effects of natural medicinal plant active ingredients (NMPAIs) on OSCC cancer, including the types of NMPAIs, anti-cancer mechanisms, involved signaling pathways, and clinical trials. The NMPAIs include terpenoids, phenols, flavonoids, glycosides, alkaloids, coumarins, and volatile oils. These active ingredients inhibit proliferation, induce apoptosis and autophagy, inhibit migration and invasion of OSCC cells, and regulate cancer immunity to exert anti-cancer effects. The mechanism involves signaling pathways such as mitogen-activated protein kinase, phosphatidylinositol 3 kinase/protein kinase B, nuclear factor kappa B, miR-22/WNT1/ß-catenin and Nrf2/Keap1. Clinically, NMPAIs can inhibit the growth of OSCC, and the combined drug is more effective. Natural medicinal plants are promising candidates for the treatment of OSCC.

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A new strategy for the high-throughput characterization of the mechanical homogeneity of metallurgical materials is proposed. Based on the principle of hydrostatic transmission and the synergistic analysis of the composition, microstructure, defects, and surface profile of the chosen material, the microstrain characteristics and changes in surface roughness after isostatic pressing were analyzed. After isostatic pressing, two types of microstrains were produced: low microstrain (surface smoothening with decreasing roughness) and large microstrain (surface roughening with increasing roughness). Furthermore, the roughness of the roughened microregions could be further classified based on the strain degree. The phenomenon of weak-interface damage with a large microstrain (plastic deformation, cleavage fracture, and tearing near nonmetallic inclusions) indicated that the surface microstrain analysis could be a new method of high-throughput characterization for microregions with relatively poor micromechanical properties. In general, the effect of isostatic pressing on the surface microstrain of heat-resistant steel provides a promising strategy for achieving high-throughput screening and statistically characterizing microregions with poor micromechanical properties, such as microregions containing microcracks, nonmetallic inclusions, pores, and other surface defects.

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Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.

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The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-resolution MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners.

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Hydrogels provide a versatile platform for biomedical material fabrication that can be structurally and mechanically fine-tuned to various tissues and applications. Applications of hydrogels in biomedicine range from highly dynamic injectable hydrogels that can flow through syringe needles and maintain or recover their structure after extrusion to solid-like wound-healing patches that need to be stretchable while providing a selective physical barrier. In this study, a toolbox is designed using thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) polymeric matrices and nanocelluloses as reinforcing agent to obtain biocompatible hydrogels with altering mechanical properties, from a liquid injectable to a solid-like elastic hydrogel. The liquid hydrogels possess low viscosity and shear-thinning properties at 25 °C, which allows facile injection at room temperature, while they become viscoelastic gels at body temperature. In contrast, the covalently cross-linked solid-like hydrogels exhibit enhanced viscoelasticity. The liquid hydrogels are biocompatible and are able to delay the in vitro release and maintain the bioactivity of model drugs. The antimicrobial agent loaded solid-like hydrogels are effective against typical wound-associated pathogens. This work presents a simple method of tuning hydrogel mechanical strength to easily adapt to applications in different soft tissues and broaden the potential of renewable bio-nanoparticles in hybrid biomaterials with controlled drug release capabilities.

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d-Amino acids are signals for biofilm disassembly. However, unexpected metabolic pathways severely attenuate the utilization of d-amino acids in biofilm disassembly, resulting in unsatisfactory efficiency. Herein, three-dimensional poly(d-amino acid) nanoparticles (NPs), which possess the ability to block intracellular metabolism, are constructed with the aim of disassembling the biofilms. The obtained poly(α-N-acryloyl-d-phenylalanine)-block-poly(ß-N-acryloyl-d-aminoalanine NPs (denoted as FA NPs) present α-amino groups and α-carboxyl groups of d-aminoalanine on their surface, which guarantees that FA NPs can effectively insert into bacterial peptidoglycan (PG) via the mediation of PG binding protein 4 (PBP4). Subsequently, the FA NPs trigger the detachment of amyloid-like fibers that connect to the PG and reduce the number of polysaccharides and proteins in extracellular polymeric substances (EPS). Finally, FA NPs damage the structural stability of EPS and lead to the disassembly of the biofilm. Based on this feature, FA NPs significantly enhance the killing efficacy of encapsulated sitafloxacin sesquihydrate (Sita) by facilitating the penetration of Sita within the biofilm, achieving complete elimination of Staphylococcal biofilm in mice. Therefore, this study strongly demonstrates that FA NPs can effectively improve biofilm disassembly efficacy and provide great potential for bacterial biofilm infection treatment.

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OBJECTIVE: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk. METHODS: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA. RESULTS: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease. CONCLUSION: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors.

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OBJECTIVES: This study aimed to delineate the ability of a plasmid, pS130-4, which harboured both hypervirulence and multidrug resistance genes, to disseminate within Klebsiella pneumoniae, as well as its potential formation mechanism. METHODS: We employed whole-genome sequencing to decipher the genetic architecture of pS130-4. Its capability to conjugate and transfer was assessed through a series of experiments, including plasmid stability, competitive growth, and growth curve analysis. Its expression stability was further evaluated using drug sensitivity, larval survival, and biofilm formation tests. RESULTS: pS130-4 contained four intact modules typical of self-transmissible plasmids. BLAST analysis revealed a sequence identity exceeding 90% with other plasmids from a variety of hosts, suggesting its broad prevalence. Our findings indicated the plasmid's formation resulted from IS26-mediated recombination, leading us to propose a model detailing the creation of this conjugative fusion plasmid housing both blaKPC-2 and hypervirulence genes. Our conjugation experiments established that pS130-4, when present in the clinical strain S130, was self-transmissible with an estimated efficiency between 10-5 and 10-4. Remarkably, pS130-4 showcased a 90% retention rate and did not impede the growth of host bacteria. Galleria mellonella larval infection assay demonstrated that S130 had pronounced toxicity when juxtaposed with high-virulence control strain NTUH-K2044 and low-toxicity control strain ATCC700603. Furthermore, pS130-4's virulence remained intact postconjugation. CONCLUSION: A fusion plasmid, encompassing both hypervirulence and multidrug resistance genes, was viable within K. pneumoniae ST11-KL64 and incurred minimal fitness costs. These insights underscored the criticality of rigorous monitoring to pre-empt the escalation and distribution of this formidable super-plasmid.

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Drinking water contamination, often caused by bacteria, leads to substantial numbers of diarrhea deaths each year, especially in developing regions. Human urine as a source of fertilizer, when handled improperly, can contaminate drinking water. One dominant bacterial pathogen in urine is Escherichia coli, which can trigger serious waterborne/foodborne diseases. Considering the prevalence of the multi-drug resistant extended-spectrum beta-lactamase (ESBL) producing E. coli, a rapid detection method for resistance is highly desired. In this work, we developed a method for quick identification of E. coli and, at the same time, capable of removal of general bacterial pathogens from human urine. A specific peptide GRHIFWRRGGGHKVAPR, reported to have a strong affinity to E. coli, was utilized to modify the PEGylated magnetic nanoclusters, resulting in a specific capture and enrichment of E. coli from the bacteria-spiked artificial urine. Subsequently, a novel luminescent probe was applied to rapidly identify the antimicrobial resistance of the collected E. coli within 30 min. These functionalized magnetic nanoclusters demonstrate a promising prospect to rapidly detect ESBL E. coli in urine and contribute to reducing drinking water contamination.

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Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

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Curcumin, an important natural component of turmeric, has been known for a long time for its antimicrobial properties. This study aimed to investigate the anti-biofilm action of the niosome-encapsulated curcumin and explore the involved anti-biofilm mechanism. In silico investigations of ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) were first performed to predict the suitability of curcumin for pharmaceutical application. Curcumin showed low toxicity but at the same time, low solubility and low stability, which, in turn, might reduce its antimicrobial activity. To overcome these intrinsic limitations, curcumin was encapsulated using a biocompatible niosome system, and an encapsulation efficiency of 97% was achieved. The synthesized curcumin-containing niosomes had a spherical morphology with an average diameter of 178 nm. The niosomal curcumin was capable of reducing multi-drug resistant (MDR) Staphylococcus aureus biofilm 2-4-fold compared with the free curcumin. The encapsulated curcumin also demonstrated no significant cytotoxicity on the human foreskin fibroblasts. To understand the interaction between curcumin and S. aureus biofilm, several biofilm-related genes were analyzed for their expression. N-acetylglucosaminyl transferase (IcaD), a protein involved in the production of polysaccharide intercellular adhesion and known to play a function in biofilm development, was found to be downregulated by niosomal curcumin and showed high binding affinity (-8.3 kcal/mol) with curcumin based on molecular docking analysis. Our study suggests that the niosome-encapsulated curcumin is a promising approach for the treatment of MDR S. aureus biofilm and can be extended to biofilms caused by other pathogens.