Exploiting Materials Binding Peptides for the Organization of Resilient Biomolecular Constructs.

Elastomers based on the resilin protein confer exceptional mechanical resilience in nature, but it remains elusive to recover the remarkable properties of these materials when they are made in the laboratory. This is possibly due to preorganized conformations of resilin in its natural setting, facilitating Tyr-based cross-linking. Here, resilin-like peptides (RLPs) are conjugated with a graphene-binding peptide, P1, to produce P1/RLP conjugates, in which the P1 domain may provide favorable preorganization on a graphene surface. Experiments using quartz crystal microbalance analysis and atomic force microscopy identified that the parent RLPs demonstrate negligible graphene binding; however, integration of the P1 with the RLPs resulted in the formation of dense, patterned bioligand overlayers on graphene. To complement this, molecular simulations revealed a notable difference in binding mode of the conjugates compared with typical materials binding peptides. Specifically, the adsorption of the P1/RLP conjugates did not focus on a few strongly bound "anchor" residues, but instead supported a more diffuse mode of binding, with many more participating residues featuring moderate contact. Analysis of the number of available Tyr residues (i.e., those not adsorbed at the surface) indicate that the RLP2-based conjugates will provide greater opportunity for cross-linking when adsorbed on graphene, providing a framework to generate patterned elastomeric materials.

Pilocarpine in the Treatment of Presbyopia: Progress, Issues, and Future Prospects.

Presbyopia is a common age-related visual impairment. With the aging of the population, the incidence of presbyopia is increasing globally, becoming a worldwide public health concern. Treatment options for presbyopia include optical lens correction, surgical intervention, and pharmacological therapy. Pharmacological treatments for presbyopia are non-invasive, reversible, and have emerged over the past decade. Following the US Food and Drug Administration's approval of 1.25% pilocarpine for presbyopia, the use of pilocarpine and its compound formulations has gained increased attention, with some drugs entering clinical phase II/III trials ( www.clinicaltrials.gov ). Therefore, this article primarily describes and analyzes the progress of research on the use of pilocarpine and its compound formulations for presbyopia, as well as the challenges that remain to be addressed. The optimal dosage form, the optimal concentration, the long-term safety, and patient compliance should be further explored, and there is a lack of multi-center evidence-based medicine research to support it. The aim of this article is to provide a reference for researchers to conduct further in-depth investigations in this area.

Learning clustering-friendly representations via partial information discrimination and cross-level interaction.

Despite significant advances in the deep clustering research, there remain three critical limitations to most of the existing approaches. First, they often derive the clustering result by associating some distribution-based loss to specific network layers, neglecting the potential benefits of leveraging the contrastive sample-wise relationships. Second, they frequently focus on representation learning at the full-image scale, overlooking the discriminative information latent in partial image regions. Third, although some prior studies perform the learning process at multiple levels, they mostly lack the ability to exploit the interaction between different learning levels. To overcome these limitations, this paper presents a novel deep image clustering approach via Partial Information discrimination and Cross-level Interaction (PICI). Specifically, we utilize a Transformer encoder as the backbone, coupled with two types of augmentations to formulate two parallel views. The augmented samples, integrated with masked patches, are processed through the Transformer encoder to produce the class tokens. Subsequently, three partial information learning modules are jointly enforced, namely, the partial information self-discrimination (PISD) module for masked image reconstruction, the partial information contrastive discrimination (PICD) module for the simultaneous instance- and cluster-level contrastive learning, and the cross-level interaction (CLI) module to ensure the consistency across different learning levels. Through this unified formulation, our PICI approach for the first time, to our knowledge, bridges the gap between the masked image modeling and the deep contrastive clustering, offering a novel pathway for enhanced representation learning and clustering. Experimental results across six image datasets demonstrate the superiority of our PICI approach over the state-of-the-art. In particular, our approach achieves an ACC of 0.772 (0.634) on the RSOD (UC-Merced) dataset, which shows an improvement of 29.7% (24.8%) over the best baseline. The source code is available at https://github.com/Regan-Zhang/PICI.

Variation of microbial necromass carbon and its potential relationship with humification during composting of chicken manure with and without biochar addition.

Microbial necromass carbon (MNC) is an important stable organic C component. However, the variation of MNC and its potential relationship with humus components in composting remains uncertain. During a 45-day chicken manure composting study with and without biochar, MNC ranged from 24.9 to 77.9 g/kg and increased significantly by 80.9 % to 133 %. MNC constituted 5.77 % to 21.3 % of total organic C, with bacterial/fungal necromass C ratio ranging from 0.82 to 1.78. The MNC/humus C ratio ranged from 0.15 to 0.55, and humic acid C showed significant positive associations with bacterial necromass C (R2 = 0.72) and fungal necromass C (R2 = 0.51). Biochar addition reduced electrical conductivity and moisture content, increased pH, and induced microbial phosphorus limitation, thereby enhancing MNC content by 29.2 % and promoting humification. Our study is the first to elucidate the relationship between microbial necromass and humus substances, providing fundamental data for advancing the microbial carbon pump theory in composting.

A Photothermal Polymeric Platform for Efficient and Safe Gene Transfection: When Polyethylenimine Collaborates with Indocyanine Green.

Gene transfection, defined by the delivery of nucleic acids into cellular compartments, stands as a crucial procedure in gene therapy. While branched polyethylenimine (PEI) is widely regarded as the "gold standard" for nonviral vectors, its cationic nature presents several issues, including nonspecific protein adsorption and notable cytotoxicity. Additionally, it often fails to achieve high transfection efficiency, particularly with hard-to-transfect cell types. To overcome these challenges associated with PEI as a vector for plasmid DNA (pDNA), the photothermal agent indocyanine green (ICG) is integrated with PEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient and safer gene transfection. The negatively charged ICG serves a dual purpose: neutralizing PEI's excessive positive charges to reduce cytotoxicity and, under near-infrared irradiation, inducing local heating that enhances cell membrane permeability, thus facilitating the uptake of PI/pDNA complexes to boost transfection efficiency. Using pDNA encoding vascular endothelial growth factor as a model, our system shows enhanced transfection efficiency in vitro for hard-to-transfect endothelial cells, leading to improved cell proliferation and migration. Furthermore, in vivo studies reveal the therapeutic potential of this system in accelerating the healing of infected wounds by promoting angiogenesis and reducing inflammation. This approach offers a straightforward and effective method for gene transfection, showing potentials for tissue engineering and cell-based therapies.

Atramacronoid A induces the PANoptosis-like cell death of human breast cancer cells through the CASP-3/PARP-GSDMD-MLKL pathways.

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

A photothermal surface modified with polyelectrolyte multilayers for gene transfection and cell harvest.

Gene transfection, which involves introducing nucleic acids into cells, is a pivotal technology in the life sciences and medical fields, particularly in gene therapy. Surface-mediated transfection, primarily targeting cells adhering to surfaces, shows promise for enhancing cell transfection by localizing and presenting surface-bound nucleic acids directly to the cells. However, optimizing endocytosis for efficient delivery remains a persistent challenge. Additionally, ensuring efficient and non-traumatic cell harvest capability is crucial for applications such as ex vivo cell-based therapy. To address these challenges, we developed a photothermal platform with enzymatic degradation capability for efficient gene transfection and cell harvest. This platform is based on carbon nanotubes (CNTs) doped with poly(dimethylsiloxane) and modified with polyelectrolyte multilayers (PEMs) containing hyaluronic acid and quaternized chitosan, allowing for substantial loading of poly(ethyleneimine)/plasmid DNA (pDNA) complexes through electrostatic interactions. Upon irradiation of near-infrared laser, the photothermal properties of CNTs enable high transfection efficiency by delivering pDNA into attached cells via a membrane disruption mechanism. The engineered cells can be harvested by treating with a non-toxic hyaluronidase solution to degrade PEMs, thus maintaining good viability for further applications. This platform has demonstrated remarkable efficacy across various cell lines (including Hep-G2 cells, Ramos cells and primary T cells), achieving a transfection efficiency exceeding 95 %, cell viability exceeding 90 %, and release efficiency surpassing 95 %, highlighting its potential for engineering living cells.

Performance of feeding black soldier fly (Hermetia illucens) larvae on shrimp carcasses: A green technology for aquaculture waste management and circular economy.

Over 944 thousand tonnes of shrimp carcasses are produced worldwide during the shrimp production cycle, and black soldier fly larvae (BSFL) are a potential solution for this shrimp carcass accumulation. In this study, we evaluated the performance of BSFL feeding on shrimp carcasses. Six combinations of wheat bran and shrimp carcass powder (with replacement increments of 20 %) and one whole shrimp carcasses treatment were tested. The bioconversion rate (27.15 ± 3.66 %; p = 0.001), crude protein (55.34 ± 1.27 %; p < 0.001), and crude lipid (14.37 ± 1.86 %; p = 0.007) values of BSFL reared on whole shrimp carcasses were significantly higher than those of BSFL reared on wheat bran. Increasing the shrimp carcass amount in the feeding media resulted in significant increases in BSFL docosahexaenoic acid (with the highest value occurring for BSFL reared on whole shrimp carcasses; 1.46 ± 0.09 %; p < 0.001). Conversely, BSFL docosahexaenoic acid was not detected for BSFL reared on wheat bran. The detected heavy metal concentrations in BSFL were below the limits of the published international guidelines for animal feed. In the obtained BSFL, Salmonella was not detected, and the mould count was <10 CFU/g. The total bacterial count (Lg transformation) of obtained BSFL ranged from 7.88 to 8.07 CFU/g, and no significant differences among all treatments (p = 0.424). Overall, this study demonstrates that BSFL-based bioconversion presents a resource recovery technology for converting shrimp carcasses into high-value nutritional biomass.

The Influence of Shelter Type and Coverage on Crayfish (Procambarus clarkii) Predation by Catfish (Silurus asotus): A Controlled Environment Study.

Procambarus clarkii is adept at using natural shelters and caves to evade attacks from predators. However, the concealment abilities and mechanisms of P. clarkii for different types of shelters under predation pressure have not yet been reported. In this study, laboratory experiments were carried out to determine the effects of different coverages (25%, 50%, and 75%) and different combinations (I-VII) of three types of shelters (PVC pipes, water grass, and stone) on the predation rhythm, behavior, and abilities of Silurus asotus on P. clarkii. The results indicated that the predation of S. asotus on P. clarkii exhibited significant rhythmicity under shelter conditions, excluding PVC pipes, 75% stone, and combination VI. Among the three types of shelters, PVC pipes provided the strongest concealment, followed by stone and water grass. With the increase in shelter coverage, the anti-predation ability of P. clarkii continued to increase, and the optimal shade rate for water grass was 50%. In the different shelter combinations, the environmental complexity had little effect on the predation activity of S. asotus on P. clarkii. These findings demonstrated that the type and abundance of shelters in the wild environment can affect the predation rhythm and activities of S. asotus on P. clarkii.

Mediating effect of psychological capital on the relationship between mental health literacy and coping styles among newly recruited nurses.

BACKGROUND: Newly recruited nurses face multiple sources of stress and their coping styles need to be focused on to ensure good mental health. This study aimed to examine the relationship among mental health literacy, psychological capital and coping styles in newly recruited nurses. METHODS: A cross-sectional study was conducted in August and September 2022. A total of 315 newly recruited nurses were recruited in a tertiary hospital in Henan Province, central China, employing the convenience sampling method. The self-reported questionnaires were sent through a QR code, including the Mental Health Literacy Scale for Healthcare Students, Psychological Capital Questionnaire, and Simplified Coping Style Questionnaire. Pearson correlation analysis was used to evaluate the relationships among the variables. Mediation analysis was performed to identify the mediating effect of psychological capital on the relationship between mental health literacy and coping styles. RESULTS: Positive coping showed a positive relationship with psychological capital and mental health literacy, while negative coping showed a negative relationship with psychological capital and mental health literacy. For positive coping, psychological capital was a partial mediator with an effect of 0.140, accounting for 62.8%. For negative coping, a full mediating effect was shown by psychological capital between mental health literacy and negative coping, with an indirect effect of -0.048. CONCLUSION: Psychological capital plays a partial and complete mediating role between mental health literacy and different coping styles among newly recruited nurses. Diversified training and personalized guidance in improving mental health literacy and increasing psychological capital simultaneously can be provided to newly recruited nurses continuously to adjust their coping styles.

Bi-functional quercetin/copper nanoparticles integrating bactericidal and anti-quorum sensing properties for preventing the formation of biofilms.

Biofilms formed by pathogenic bacteria present a persistent risk to human health. While the eradication of matured biofilms remains a formidable challenge, delaying or preventing their formation, which is coordinately regulated by quorum sensing (QS), presents a simpler and more advantageous strategy. Quercetin, a naturally occurring compound with anti-QS properties, has the potential to act as an antibiofilm agent. However, it is plagued by certain inherent drawbacks, including poor water solubility and limited bioavailability. Furthermore, solely blocking QS is not enough to prevent biofilm formation because it lacks bactericidal properties. To address these difficulties, we fabricated bi-functional nanoparticles through the co-assembly of quercetin and copper ions in a facile manner. The resulting quercetin/copper nanoparticles (QC NPs) demonstrated minimal cytotoxicity and hemolysis in vitro. In response to the low pH of microenvironments that were populated by bacterial colonies, the QC NPs underwent disassembly to release copper ions and quercetin. The former exterminated bacteria by disrupting the integrity of the cell membrane, while the latter disrupted the processes involved in QS that are responsible for the biofilm by downregulating the expression of specific genes, effectively preventing the formation of biofilms by both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. In addition, the QC NPs were integrated into a bacterial cellulose membrane. The composite membrane proved to be highly effective at inhibiting biofilm formation in vitro and demonstrated the ability to reduce inflammatory responses and accelerate the healing of bacteria-infected wounds in vivo. Overall, the bi-functional QC NPs hold great potential for use in addressing the challenges associated with the management of bacterial biofilms.

New caffeoyl derivatives with potent DPPH radical scavenging activity from Elephantopus tomentosus.

Eight new caffeoyl derivatives, elephantomentosides A-H (1 - 8), together with ten known ones (9 - 18), were isolated from the whole plant of Elephantopos tomentosus L. Their structures were elucidated using detailed spectroscopic analysis. Structurally, compounds 1 - 8 are composed of ß-D-glucopyranose, and almost all of the substituent positions are at the C-1' and C-4' of glucopyranose. The anti-inflammatory and antioxidant activities of all isolated compounds were evaluated in vitro. Compounds 9-10, 13-15, and 17-18 exhibited significant DPPH scavenging capacity with IC50 values in the range of 10.01-25.07 µM, in comparison with Vc (IC50, 17.98 µM).

Dupilumab Reduces Asthma Disease Burden and Recurrent SCS Use in Patients with CRSwNP and Coexisting Asthma.

Purpose: Dupilumab significantly reduced the requirement for systemic corticosteroids (SCS) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and coexisting asthma typically have a higher disease burden and have more difficulty in managing disease. Here, we report an analysis of asthma outcomes and SCS use in patients with CRSwNP and coexisting asthma. Patients and Methods: This was a post hoc analysis of the randomized, placebo-controlled SINUS-24 and SINUS-52 studies (NCT02912468/NCT02898454) in patients with severe CRSwNP and coexisting asthma (patient self-reported) from the pooled intention-to-treat population randomized to dupilumab 300 mg every 2 weeks or placebo. On-treatment SCS use was estimated using Kaplan-Meier analysis. Forced expiratory volume in 1 s (FEV1), percent predicted FEV1, and the 6-item Asthma Control Questionnaire (ACQ-6) were assessed at baseline and Week 24 (pooled SINUS-24/52) in patients with/without history of asthma exacerbation or prior SCS use. Results: Of 337 patients with coexisting asthma, 88 (26%) required on-treatment SCS use. The requirement for on-treatment SCS use for any reason was significantly lower with dupilumab (20/167 patients; 12%) vs placebo (68/170; 40%); hazard ratio (95% confidence interval) 0.248 (0.150-0.409); p < 0.0001. The most frequent reasons for SCS use were nasal polyps (dupilumab 3% and placebo 27%) and asthma (2% and 9%, respectively). FEV1, percent predicted FEV1, and ACQ-6 were all significantly improved at Week 24 with dupilumab vs placebo irrespective of history of asthma exacerbation or prior SCS use (all p < 0.01). Conclusion: Dupilumab significantly reduced the requirement for SCS and improved asthma outcomes irrespective of history of asthma exacerbation or prior SCS use vs placebo in patients with CRSwNP and coexisting asthma, demonstrating concomitant reduction of SCS use and asthma disease burden in these patients.

Eco-Friendly Solvent Engineered CsPbI2.77 Br0.23 Ink for Large-Area and Scalable High Performance Perovskite Solar Cells.

The performance of large-area perovskite solar cells (PSCs) has been assessed for typical compositions, such as methylammonium lead iodide (MAPbI3 ), using a blade coater, slot-die coater, solution shearing, ink-jet printing, and thermal evaporation. However, the fabrication of large-area all-inorganic perovskite films is not well developed. This study develops, for the first time, an eco-friendly solvent engineered all-inorganic perovskite ink of dimethyl sulfoxide (DMSO) as a main solvent with the addition of acetonitrile (ACN), 2-methoxyethanol (2-ME), or a mixture of ACN and 2-ME to fabricate large-area CsPbI2.77 Br0.23 films with slot-die coater at low temperatures (40-50 °C). The perovskite phase, morphology, defect density, and optoelectrical properties of prepared with different solvent ratios are thoroughly examined and they are correlated with their respective colloidal size distribution and solar cell performance. The optimized slot-die-coated CsPbI2.77 Br0.23 perovskite film, which is prepared from the eco-friendly binary solvents dimethyl sulfoxide:acetonitrile (0.8:0.2 v/v), demonstrates an impressive power conversion efficiency (PCE) of 19.05%. Moreover, the device maintains ≈91% of its original PCE after 1 month at 20% relative humidity in the dark. It is believed that this study will accelerate the reliable manufacturing of perovskite devices.

Mechanism of polyethylene and biodegradable microplastic aging effects on soil organic carbon fractions in different land-use types.

Microplastics (MPs) are widely present in terrestrial ecosystems, but knowledge about the aging characteristics of MPs in different land-use types and their impact on soil organic carbon fractions is still limited. Polyethylene (PE) and biodegradable MPs (Poly propylene carbonate and Polybutylene adipate terephthalate synthetic material (PPC + PBAT, Bio)), at 0 %, 0.03 %, and 0.3 % (w/w) dosages, were added to grassland, farmland, and facility soils for eight-week incubation. The aging degree of MPs was explored by quantifying the carbonyl index (CI). Soil organic C fractions such as SOC, particulate organic carbon (POC), mineral-associated organic carbon (MAOC), and microbial-derived C were analyzed. MPs underwent rapid aging after incubation, and the CI value for 0.03 % PE-MPs increased from 0.05 to 0.27 (farmland) and 0.26 (facility) (p < 0.05). The aging degree of 0.03 % and 0.3 % Bio-MPs was most significant in grassland, with CI decreasing by 46.6 % and 69.0 %, respectively. The CI of MPs were negatively correlated with their dosage. The 0.03 % and 0.3 % PE-MPs decreased soil organic carbon (SOC) content by 7.4 % and 8.2 % in grassland, and 3.0 % and 6.0 % in the facility (p < 0.05). POC content of farmland and facility soil was negatively correlated with PE-MPs' CI (p < 0.05). The 0.03 % PE and Bio-MPs decreased fungal necromass C (FNC) by 0.40 and 0.05 g kg-1 in grassland and 0.48 and 0.21 g kg-1 in farmland. Besides, the dosage of MPs regulated FNC content through soil pH, nutrients, and extracellular enzyme activity, either directly or indirectly, ultimately affecting the soil C pool. Therefore, this study demonstrates that MPs strongly affect SOC dynamics by influencing soil microbial enzyme activity and fungal necromass.

Host-Guest-Interaction Enhanced Nitric Oxide Photo-Generation within a Pillar[5]arene Cavity for Antibacterial Gas Therapy.

Supramolecular macrocycles with intrinsic cavities have been widely explored as containers to fabricate versatile functional materials via specific host-guest recognitions. However, relatively few studies have focused on the modulation of guest reactivity within a macrocyclic cavity. Here, we demonstrate the confinement effect of pillar[5]arene with an electron-rich and precise cavity that can dramatically enhance guest photoactivity and nitric oxide (NO) generation upon visible light irradiation. Mechanism studies reveal that it is achieved through increasing the ground state nitro-aromatic torsion angle, suppressing the intersystem crossing relaxation path of the S1 state, and accelerating the isomerization reaction path of guest molecules. This NO-generating system displays broad-spectrum antibacterial, biofilm inhibition, and dispersal activities. Moreover, it can accelerate the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in vivo.

Feeding mediated web-building plasticity in a cobweb spider.

Behavioral plasticity has been proposed as a means by which animals alter their phenotypes in response to changing conditions. Animals may display behavioral plasticity as a consequence of environmental variation. The detritus-based, bell-shaped cobweb spider Campanicola campanulata is an ideal model to study behavioral plasticity, because its web architecture is easy to be quantified, and the functions of different parts of the web are clear. Though the plasticity of cobweb architecture has been reported in a few species, retreats as important defensive structures have rarely been considered before because retreats in most cobwebs are relatively small compared with the web size. We studied the web-building behaviors of C. campanulata under different feeding regimes. We set up 3 spider treatments with different feeding conditions: marginally well fed, moderately well fed, and extremely well fed, and observed the differences in the web architecture among them. In addition, we measured the mechanical properties of anchor silk, and also calculated the foraging and defense investment of the spiders. The results showed that marginally well-fed spiders build cobwebs with significantly longer length of anchor silk, lower retreat to the ground, more number and longer gumfooted lines, and larger capture area, while extremely well-fed spiders build cobwebs with significantly bigger retreat volume and higher height of retreat to the ground. In addition, marginally well-fed spiders invest significantly less during cobweb construction. However, there was no significant difference between the breaking force and elongation at break in anchor silk among different treatments. These results demonstrated that marginally well-fed spiders invest more in foraging, and extremely well-fed spiders invest more in defense, and the spider made a balance between foraging and predator avoidance in response to changes in physiological state. Our study strengthens the current understanding of web construction in cobweb spiders, especially those facing high costs during retreat construction.

Patient satisfaction with humanistic nursing in Chinese secondary and tertiary public hospitals: a cross-sectional survey.

Background: Humanistic care pertains to the abilities, attitudes, and behaviors central to patient-centered care, contributing to patients' sense of safety and wellbeing. This study aimed to assess the satisfaction of patients with humanistic nursing care in Chinese secondary and tertiary public hospitals. Methods: A national cross-sectional survey was conducted across 30 provinces and 83 hospitals in China. Patient satisfaction with humanistic care was assessed using the Methodist Health Care System Nurse Caring Instrument (NCI), which encompasses 20 items across 12 dimensions. Each item was rated on a 7-point Likert scale, yielding a total score of 140. Multiple linear regression analysis was employed to identify factors associated with patients' satisfaction. Results: Moderate satisfaction (mean score 91.26 ± 13.14) with humanistic nursing care was observed among the 17,593 participants. Factors significantly associated with patient satisfaction included age, hospital type, presence of children, educational attainment, place of residence, family monthly income, and medical insurance type. Conclusion: The study findings highlight the importance of tailored interventions, evidence-based practice guidelines, and patient-centered care in improving patients' satisfaction with humanistic nursing care. Continuous emphasis on nursing education and professional development is crucial for enhancing humanistic care and patient satisfaction.

Enhanced Intracellular Delivery and Cell Harvest Using a Candle Soot-Based Photothermal Platform with Dual-Stimulus Responsiveness.

Intracellular delivery of bioactive macromolecules and functional materials plays a crucial role in fundamental biological research and clinical applications. Nondestructive and efficient harvesting of engineered cells is also required for some specific applications. In this work, we develop a multifunctional platform based on candle soot modified with copolymer brushes containing temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and sugar-responsive phenylboronic acid (PBA) components. This platform possesses a high cell adhesion capacity due to the inherent hierarchical structure of candle soot and the formation of boronate ester bonds between the PBA groups and glycoproteins on the cell membrane. Under the irradiation of a near-infrared laser, the excellent light-to-heat conversion ability of candle soot enables the highly efficient delivery of macromolecules into diverse cells (including hard-to-transfect cells) attached to the surface via a photothermal-poration mechanism. Owing to the temperature-responsive properties of PNIPAAm and the sugar-responsive properties of PBA, the engineered cells could be harvested nondestructively from the platform by a mild treatment using a cold fructose solution. A proof-of-concept experiment demonstrates that fibroblasts attached to the surface could be transfected by a functional plasmid encoding basic fibroblast growth factor and then harvested efficiently and recultured with improved proliferation and migration ability. The whole delivery-harvesting process required less than 1 h, allowing the cells to be engineered without compromising their viability. This platform thus provides a widely applicable method for both the intracellular delivery of diverse macromolecules efficiently as well as harvesting engineered cells simply and safely, holding great potential for biomedical applications.

A near-infrared light-triggered nano-domino system for efficient biofilm eradication: Activation of dispersing and killing functions by generating nitric oxide and peroxynitrite via cascade reactions.

One of the serious threats to global public health is the bacterial biofilm, which results in numerous persistent and recurrent infections. Herein, we proposed a near-infrared (NIR) light-triggered "nano-domino" system with "dispersing and killing" functionality for biofilm eradication. The nanoplatform was fabricated by the self-assembly of chitosan conjugated with L-arginine (L-Arg, a natural nitric oxide (NO) donor) and indocyanine green (ICG, a phototherapy agent). Using an NIR irradiation "trigger", a series of reactive oxygen species (ROS) including singlet oxygen (1O2), hydrogen peroxide (H2O2), and superoxide anions (·O2-), as well as heat were generated from ICG aggregates. Subsequently, 1O2 and H2O2 catalyzed L-Arg to produce NO, which dispersed the biofilm and reacted with ·O2- to form peroxynitrite to kill bacteria with ROS collaboratively. Meanwhile, the generated heat increased the permeability of bacterial membranes, aggravating the damage to biofilm bacteria. The experiments on biofilm eradication demonstrated that this "nano-domino" system was capable to eradicate over 99.99% of biofilms formed by Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa under 5-min NIR irradiation. Notably, these integrated benefits allowed the system to promote the healing of MRSA biofilm-infected wounds in vivo with negligible toxicity. Overall, this reported NIR-triggered "nano-domino" system holds great promise for addressing the difficulties associated with bacterial biofilm eradication. STATEMENT OF SIGNIFICANCE: Novel agents for biofilm eradication are urgently needed due to the alarming rise in antimicrobial resistance to conventional antibiotics and the critical shortage of new drugs. In this study, we created a nano-domino system that uses near-infrared (NIR) light as a trigger to eradicate mature biofilms. In response to a short-term NIR irradiation, the proposed nanoplatform could generate nitric oxide and peroxynitrite to disperse the biofilm and kill the bacteria inside, respectively, leading to efficient eradication of Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms with minimal cytotoxicity. The findings, therefore, indicate that this nanoplatform with enhanced antibiofilm performance might provide a reliable and promising solution to biofilm-related problems.