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Background: Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia. Methods: C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses. Results: LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination. Conclusions: Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections. [ABSTRACT FROM AUTHOR]

Aims To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage. Methods and results Hemolysis tests were used to evaluate Forsythoside B's inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections. Conclusions Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae. [ABSTRACT FROM AUTHOR]

This experiment aimed to investigate the effects of emodin on the physiological responses and antioxidant gene expression of Wuchang bream infected with Aeromonas hydrophila. The experimental diets were prepared with supplementing 0, 30, 100 and 150 mg kg-1 emodin to basal (control) diet respectively, and fed to fish with initial weight of 50.4 ± 2.35 g. All fish were divided into five experimental groups: uninfected fish fed with basal control diet (negative control, NC), infected fish fed with the diet supplemented with 0 (positive control group, PC), 30, 100, and 150 mg kg-1 emodin. The fish were reared for 14 days, sampled at different time points and then analyzed. The results showed that the physiological responses and related antioxidant gene expression of infected Wuchang bream were significantly influenced by the dosage of added emodin and the feeding duration (P < 0.05). Comparing to the positive control group, emodin could inhibit the levels of cortisol (COR), triiodothyronine (T3), and thyroxine (T4) in infected Wuchang bream, with hormone levels reaching equilibrium in the shortest time at 30 and 100 mg kg-1 emodin supplementation. Meanwhile, emodin significantly affected alkaline phosphatase (AKP) activity, glucose (Glu) and triglyceride (TG) contents, and related antioxidant gene expression in infected Wuchang bream (P < 0.05), with the best effect observed at 100 mg kg-1 emodin supplementation in the diet. In conclusion, the supplementation of 100 mg/kg emodin to diet can enhance the resistance of Wuchang bream to A. hydrophila infection via promoting physiological metabolism and antioxidant capacity. [ABSTRACT FROM AUTHOR]

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Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Infected bone defect is a formidable clinical challenge. Conventional approaches to prevention and treatment for infected bone defects are unsatisfactory. The key elements of the treatment are bone defect reconstruction, anti-infection, and osteogenesis. Conventional treatment methods remain unsatisfactory owing to the absence of composite integrating materials with anti-infective, and osteogenic activities as well as proper mechanical strength at the same time. In this study, we fabricated a vancomycin-encapsulated hydrogel with bacteria-responsive release properties combined with a shaved porous (submicron-micron) three-dimensional-printed Ti6Al4V implant. The implant surface, modified with submicron-sized pores through microarc oxidation (MAO), showed enhanced osteogenic activity and integrated well with the hydrogel drug release system, enabling sustained vancomycin release. In vitro experiments underscored the commendable antibacterial ability, biosafety, and osteoinductive potential. Effective antibacterial and osteogenic abilities of the implant were further demonstrated in vivo in infected rabbit bone defects. These results showed that the vancomycin-encapsulated hydrogel-loaded microarc-oxidized 3D-printed porous Ti6Al4V can repair the infected bone defects with satisfactory anti-infection and osseointegration effects.

Abstract Background Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia. Methods C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses. Results LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination. Conclusions Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.

Qinchuan Li,1 Wenju Guan,2 Jian Zhang,2 Min Chen,3 Ya Zou1 1Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 2Department of Oncology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 3Sichuan Academy of Medical Sciences. Department of Pharmacy, Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Ya Zou, Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China, Email zouya_1214@163.comBackground: Patients with nasopharyngeal carcinoma (NPC) combined with non-tuberculous Mycobacteria-pulmonary disease (NTM-PD) are very rare in the clinic, and our case is the first patient with NPC combined with NTM-PD. For oncologists, rapid control of the symptoms of infection is essential to the treatment of the primary disease.Case Presentation: A 58-year-old man who developed a NTM-PD after chemotherapy for nasopharyngeal carcinoma. Granulocytosis after chemotherapy is a major factor in the development of various infectious diseases. Nasopharyngeal tumor was found on MRI of the patient’s head, and nasopharyngeal malignant tumor was considered after pathological examination after endoscopic resection of intranasal lesion, and then nasopharyngeal non-keratonic carcinoma (T4N1M0, stage IV) was confirmed in the department of oncology. The patient developed bone marrow suppression after chemotherapy and was admitted to hospital due to septic shock. Chest CT examination indicated pulmonary infection, and empirical antibiotic treatment was not effective. The NGS results showed that the patient was infected with Mycobacterium abscess. We treated with cefoxitin followed by moxifloxacin to reduce the lung lesions significantly.Conclusion: NPC with NTM-PD is very rare, and the treatment of NTM-PD is very important for the prognosis of the patient’s primary disease. Our study provides experience for anti-infection treatment of patients with immunosuppression.Keywords: nasopharyngeal carcinoma, immunosuppressed, NTM, anti-infection, cefoxitin, moxifloxacin

Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro. In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

Aniba rosaeodora essential oil (RO) has been traditionally used in natural medicine as a substitute for antibiotics due to its notable antidepressant and antibacterial properties. Salmonella , a prevalent pathogen in foodborne illnesses, presents a major challenge to current antibiotic treatments. However, the antibacterial efficacy and mechanisms of action of RO against Salmonella spp. remain underexplored. This study aims to elucidate the chemical composition of RO, evaluate its antibacterial activity and mechanisms against Salmonella in vitro , and further delineate its anti-inflammatory mechanisms in vivo during Salmonella infection. Gas chromatography-mass spectrometry (GC-MS) was utilized to characterize the chemical constituents of RO. The antibacterial activity of RO was assessed using minimal inhibitory concentration (MIC) and time-kill assays. Various biochemical assays were employed to uncover the potential bactericidal mechanisms. Additionally, mouse and chick models of Salmonella infection were established to investigate the prophylactic effects of RO treatment. RO exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with an MIC of 4 mg·mL−1 for Salmonella spp. RO treatment resulted in bacterial damage through the disruption of lipid and purine metabolism. Moreover, RO reduced injury and microbial colonization in infected mice and chicks. RO treatment also modulated the host inflammatory response by inhibiting proinflammatory pathways. In conclusion, our findings demonstrate that RO is effective against Salmonella infection, highlighting its potential as an alternative to antibiotics for antibacterial therapy. [ABSTRACT FROM AUTHOR]

Ribosomal protein SA (RPSA) plays multiple roles in cells, including ribosomal biogenesis and translation, cellular migration, and cytoskeleton reorganization. RPSA is crucial in the process of pathogen infection. Extensive research has examined RPSA's role in pathogen adhesion and invasion, but its broader functions, particularly its anti-infective capabilities, have garnered increasing attention in recent years. This dual role is closely related to its structural domains, which influence its localization and function. This review summarizes key research findings concerning the functional domains of RPSA and analyzes the relationship between its membrane localization and structural domains. Additionally, the functional implications of RPSA are categorized based on its different localizations during pathogen infection. Specifically, when RPSA is located on the cell surface, it promotes pathogen adhesion and invasion of host cells; conversely, when RPSA is located intracellularly, it exhibits anti-infective properties. Overall, RPSA shows a dual nature, both in facilitating pathogen invasion of the host and in possessing the ability to resist pathogen infection. This review comprehensively examines the dual role of RPSA in pathogen infection by analyzing its structural domains, localization, and interactions with cellular and pathogen molecules. Our aim is to update and deepen researchers' understanding of the various functions of RPSA during pathogen infection. [ABSTRACT FROM AUTHOR]

Electron spinning polarization has garnered increased attention for its potential to enhance device properties. However, its application in life health, specifically in anti‐infection and tissue repair, remains under‐explored. In this study, a ferromagnetic heterojunction CF (Fe3O4/TiO2) is constructed with spin‐polarized electrons, demonstrating efficient antibiosis performance with ultrasound (US) assistance. The antibacterial mechanism is elucidated as follows: spin‐polarized metallic states of Fe3O4 induce an asymmetric distribution in the electron spin state of TiO2, increasing the density of states of spin‐polarized electrons near the Fermi level of CF. Under US treatment, the built‐in electric field and spin‐polarized electrons in CF synergistically suppress the recombination of sono‐activated carriers, promoting reactive oxygen species (ROS) production. Simultaneously, the bacterial membrane is influenced by the micromagnetic field induced by spin‐polarized electrons, causing a severe disturbance in the bacterial respiratory chain. The combined damage from ROS and disturbed respiratory chain results in bacterial death. Fortunately, the micromagnetic field built by CF activates specific mechanosensitive ion channels, including TREK1, Piezo1, and related pathways, enhancing osteoblast differentiation. Sonotherapy using CF exhibits an excellent therapeutic effect in treating osteomyelitis. This study provides novel insights into manipulating spin electrons for applications in life health. [ABSTRACT FROM AUTHOR]

Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro , suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma. [Display omitted] [ABSTRACT FROM AUTHOR]

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants. [ABSTRACT FROM AUTHOR]

Dikdik Kurnia,1 Seftiana Lestari,1 Tri Mayanti,1 Meirina Gartika,2 Denny Nurdin3 1Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, Indonesia; 2Department of Pediatric Dentistry, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia; 3Departement of Conservative Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Dikdik Kurnia, Email dikdik.kurnia@unpad.ac.idAbstract: The WHO Global Status Report on Oral Health 2022 reveals that oral diseases caused by infection with oral pathogenic microorganisms affect nearly 3.5 billion people worldwide. Oral health problems are caused by the presence of S. mutans, S. sanguinis, E. faecalis and C. albicans in the oral cavity. Synthetic anti-infective drugs have been widely used to treat oral infections, but have been reported to cause side effects and resistance. Various strategies have been implemented to overcome this problem. Synthetic anti-infective drugs have been widely used to treat oral infections, but they have been reported to cause side effects and resistance. Therefore, it is important to look for safe anti-infective alternatives. Ethnobotanical and ethnopharmacological studies suggest that Red Betel leaf (Piper crocatum Ruiz & Pav) could be a potential source of oral anti-infectives. This review aims to discuss the pathogenesis mechanism of several microorganisms that play an important role in causing health problems, the mechanism of action of synthetic oral anti-infective drugs in inhibiting microbial growth in the oral cavity, and the potential of red betel leaf (Piper crocatum Ruiz & Pav) as an herbal oral anti-infective drug. This study emphasises the importance of researching natural components as an alternative treatment for oral infections that is more effective and can meet global needs.Keywords: Piper crocatum, anti-infection, antibacterial, antifungal, oral pathogen

Abstract Symbiotic microbial communities are crucial for human health, and dysbiosis is associated with various diseases. Plant-derived nanovesicles (PDNVs) have a lipid bilayer structure and contain lipids, metabolites, proteins, and RNA. They offer unique advantages in regulating microbial community homeostasis and treating diseases related to dysbiosis compared to traditional drugs. On the one hand, lipids on PDNVs serve as the primary substances that mediate specific recognition and uptake by bacteria. On the other hand, due to the multifactorial nature of PDNVs, they have the potential to enhance growth and survival of beneficial bacterial while simultaneously reducing the pathogenicity of harmful bacteria. In addition, PDNVs have the capacity to modulate bacterial metabolism, thus facilitating the establishment of a harmonious microbial equilibrium and promoting stability within the microbiota. These remarkable attributes make PDNVs a promising therapeutic approach for various conditions, including periodontitis, inflammatory bowel disease, and skin infection diseases. However, challenges such as consistency, isolation methods, and storage need to be addressed before clinical application. This review aims to explore the value of PDNVs in regulating microbial community homeostasis and provide recommendations for their use as novel therapeutic agents for health protection. Graphical Abstract

Jingfang Granule (JFG), a traditional Chinese medicine, is frequently employed in clinical settings for the treatment of infectious diseases. Nevertheless, the anti-aging and anti-infection effects of JFG remain uncertain. In the present study, these effects were evaluated using the Caenorhabditis elegans (C. elegans) N2 as a model organism. The results demonstrated that JFG significantly increased the median lifespan of C. elegans by 31.2% at a dosage of 10 mg/mL, without any discernible adverse effects, such as alterations in the pharyngeal pumping rate or nematode motility. Moreover, JFG notably increased oviposition by 11.3%. Subsequent investigations revealed that JFG enhanced oxidative stress resistance in C. elegans by reducing reactive oxygen species levels and significantly improved survival rates in nematodes infected with Pseudomonas aeruginosa ATCC 9027. These findings suggest that JFG delays reproductive senescence in C. elegans and protects them from oxidative stress, thereby extending their lifespan. Additionally, JFG improves the survival of P. aeruginosa-infected nematodes. Consequently, JFG has potential as a candidate for the development of anti-aging and anti-infection functional medicines. [ABSTRACT FROM AUTHOR]

Symbiotic microbial communities are crucial for human health, and dysbiosis is associated with various diseases. Plant-derived nanovesicles (PDNVs) have a lipid bilayer structure and contain lipids, metabolites, proteins, and RNA. They offer unique advantages in regulating microbial community homeostasis and treating diseases related to dysbiosis compared to traditional drugs. On the one hand, lipids on PDNVs serve as the primary substances that mediate specific recognition and uptake by bacteria. On the other hand, due to the multifactorial nature of PDNVs, they have the potential to enhance growth and survival of beneficial bacterial while simultaneously reducing the pathogenicity of harmful bacteria. In addition, PDNVs have the capacity to modulate bacterial metabolism, thus facilitating the establishment of a harmonious microbial equilibrium and promoting stability within the microbiota. These remarkable attributes make PDNVs a promising therapeutic approach for various conditions, including periodontitis, inflammatory bowel disease, and skin infection diseases. However, challenges such as consistency, isolation methods, and storage need to be addressed before clinical application. This review aims to explore the value of PDNVs in regulating microbial community homeostasis and provide recommendations for their use as novel therapeutic agents for health protection. [ABSTRACT FROM AUTHOR]

Infection and poor osteogenesis are two major causes of implant failure. Surface modification strategy provides solutions to the above problems. However, the functional requirements at different biological stages during infectious bone repair and the oxidative stimulation caused by reactive oxygen species (ROS) in an inflammatory environment pose challenges to the existing approaches. Layer-by-layer (LbL) self-assembly realizes layer by layer superposition and time-dependent acting of different bioactive components, but is demanding to functional groups. Tannic acid (TA) owns abundant phenolic hydroxyl groups, endowing various firm chemical bindings and excellent antioxidant property. To this end, we developed a time-dependent and antioxidant multifunctional coating via TA mediated LbL self-assembly. This layer exhibited higher ROS removal capacity and stronger binding ability. Furthermore, it showed rapid and excellent antibacterial ability of over 85 % against Staphylococcus aureus and Escherichia coli at 24 h, which additionally promoted osteogenic differentiation in vitro in long term. Moreover, the coating exhibited outstanding antibacterial and bone regeneration performance in vivo as well. Thus, this study is expected to provide an antioxidant and time-dependent multifunctional platform for surface modification engineering of dental and orthopedic implantation, as well as other potential biological material designs.

Summary: Background: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. Methods: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. Findings: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. Interpretation: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Funding: Shown in Acknowledgements.

Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860–2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860–2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.

Abstract Autophagy is a self-renewal mechanism that maintains homeostasis and can promote tissue regeneration by regulating inflammation, reducing oxidative stress and promoting cell differentiation. The interaction between biomaterials and tissue cells significantly affects biomaterial-tissue integration and tissue regeneration. In recent years, it has been found that biomaterials can affect various processes related to tissue regeneration by regulating autophagy. The utilization of biomaterials in a controlled environment has become a prominent approach for enhancing the tissue regeneration capabilities. This involves the regulation of autophagy in diverse cell types implicated in tissue regeneration, encompassing the modulation of inflammatory responses, oxidative stress, cell differentiation, proliferation, migration, apoptosis, and extracellular matrix formation. In addition, biomaterials possess the potential to serve as carriers for drug delivery, enabling the regulation of autophagy by either activating or inhibiting its processes. This review summarizes the relationship between autophagy and tissue regeneration and discusses the role of biomaterial-based autophagy in tissue regeneration. In addition, recent advanced technologies used to design autophagy-modulating biomaterials are summarized, and rational design of biomaterials for providing controlled autophagy regulation via modification of the chemistry and surface of biomaterials and incorporation of cells and molecules is discussed. A better understanding of biomaterial-based autophagy and tissue regeneration, as well as the underlying molecular mechanisms, may lead to new possibilities for promoting tissue regeneration. Video Abstract

Abstract Marine natural products (MNPs) and marine organisms include sea urchin, sea squirts or ascidians, sea cucumbers, sea snake, sponge, soft coral, marine algae, and microalgae. As vital biomedical resources for the discovery of marine drugs, bioactive molecules, and agents, these MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, cancer treatment, and improvement of human immunity. This article reviews the role of MNPs on anti-infection of coronavirus, SARS-CoV-2 and its major variants (such as Delta and Omicron) as well as tuberculosis, H. Pylori, and HIV infection, and as promising biomedical resources for infection related cardiovascular disease (irCVD), diabetes, and cancer. The anti-inflammatory mechanisms of current MNPs against SARS-CoV-2 infection are also discussed. Since the use of other chemical agents for COVID-19 treatment are associated with some adverse effects in cardiovascular system, MNPs have more therapeutic advantages. Herein, it’s time to protect this ecosystem for better sustainable development in the new era of ocean economy. As huge, novel and promising biomedical resources for anti-infection of SARS-CoV-2 and irCVD, the novel potential mechanisms of MNPs may be through multiple targets and pathways regulating human immunity and inhibiting inflammation. In conclusion, MNPs are worthy of translational research for further clinical application. Graphical Abstract

Marine natural products (MNPs) and marine organisms include sea urchin, sea squirts or ascidians, sea cucumbers, sea snake, sponge, soft coral, marine algae, and microalgae. As vital biomedical resources for the discovery of marine drugs, bioactive molecules, and agents, these MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, cancer treatment, and improvement of human immunity. This article reviews the role of MNPs on anti-infection of coronavirus, SARS-CoV-2 and its major variants (such as Delta and Omicron) as well as tuberculosis, H. Pylori, and HIV infection, and as promising biomedical resources for infection related cardiovascular disease (irCVD), diabetes, and cancer. The anti-inflammatory mechanisms of current MNPs against SARS-CoV-2 infection are also discussed. Since the use of other chemical agents for COVID-19 treatment are associated with some adverse effects in cardiovascular system, MNPs have more therapeutic advantages. Herein, it's time to protect this ecosystem for better sustainable development in the new era of ocean economy. As huge, novel and promising biomedical resources for anti-infection of SARS-CoV-2 and irCVD, the novel potential mechanisms of MNPs may be through multiple targets and pathways regulating human immunity and inhibiting inflammation. In conclusion, MNPs are worthy of translational research for further clinical application. [ABSTRACT FROM AUTHOR]

Hemostatic materials facilitate rapid hemostasis and significantly mitigate the potential of fatal hemorrhage in civilian and military traumas. However, most existing hemostatic materials are limited in material‐dependent forms and fail to integrate multifunctionality, thus constraining their versatility for differing settings and wound healing capacity. Herein, a facile, versatile armor strategy is proposed to endow various biomaterials with rapid hemostasis, infection prevention, and tissue healing capabilities. The armor is fabricated on the surface of substrates first through chemical cross‐linking of adhesive catechol (phenol) and collagen (polyamine) inspired by insect sclerotization, followed by zinc ions (Zn2+) chelation based on mussel‐inspired metal‐phenol coordination chemistry, referred to "metal‐phenol‐polyamine system". This armor facilitates clot formation by promoting platelet aggregation and activating both intrinsic and extrinsic coagulation pathways. Moreover, the integrated Zn2+ endows the armor with potent antibacterial properties against both Gram‐positive and Gram‐negative bacteria. Consequently, this strategy armors a hemostatic sponge that effectively controls bleeding in rabbit hemorrhage models and successfully facilitates the complete healing of epidermal traumas in rats within 14 days. This metal‐phenol‐polyamine system‐assisted armor provides a potential and universal strategy for efficient hemostasis and wound healing. [ABSTRACT FROM AUTHOR]

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

Abstract Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.

Additively manufactured biodegradable zinc (Zn) scaffolds have great potential to repair infected bone defects due to their osteogenic and antibacterial properties. However, the enhancement of antibacterial properties depends on a high concentration of dissolved Zn2+, which in return deteriorates osteogenic activity. In this study, a vancomycin (Van)-loaded polydopamine (PDA) coating was prepared on pure Zn porous scaffolds to solve the above dilemma. Compared with pure Zn scaffolds according to comprehensive in vitro tests, the PDA coating resulted in a slow degradation and inhibited the excessive release of Zn2+ at the early stage, thus improving cytocompatibility and osteogenic activity. Meanwhile, the addition of Van drug substantially suppressed the attachment and proliferation of S. aureus and E. coli bacterial. Furthermore, in vivo implantation confirmed the simultaneously improved osteogenic and antibacterial functions by using the pure Zn scaffolds with Van-loaded PDA coating. Therefore, it is promising to employ biodegradable Zn porous scaffolds with the proposed drug-loaded coating for the treatment of infected bone defects.

ABSTRACT Salmonella enterica is an important zoonotic intracellular bacterial pathogen that is capable of causing infections ranging from localized gastroenteritis to fatal systemic infection in humans and food-producing animals. The increasing antibiotic resistance in Salmonella isolates, especially the emergence of MDR and newer XDR strains, has compromised the efficacy of conventional antimicrobial therapy for Salmonella infections. Hence, it is desirable to develop alternative therapeutic means to tackle the antimicrobial resistance crisis. In this study, we screened plant-derived compounds to identify inhibitors of Salmonella invasion of host cells. These efforts identified fisetin as a possible protector against infection. Further mechanistic studies revealed that fisetin suppressed the function of type III secretion system 1 (T3SS-1), the virulence determinant critical for Salmonella invasion. Fisetin appears to interfere with the interaction between HilD and its relevant promoters, thereby decreasing the transcription of hilA, the central transcriptional regulator that functions to activate the expression of T3SS-1 effector proteins and structural elements. In addition, administration of fisetin in the Salmonella murine infection model resulted in reduced bacterial colonization, alleviation of histopathological destruction, and decreased proinflammatory cytokine levels. Taken together, our study establishes that the natural compound fisetin can be used as a lead compound for the development of anti-Salmonella drugs targeting T3SS-1. IMPORTANCE Salmonella spp. remains a major worldwide health concern that causes significant morbidity and mortality in both humans and animals. The spread of antimicrobial resistant strains has declined the efficacy of conventional chemotherapy. Thus, novel anti-infection drugs or strategies are needed. Anti-virulence strategy represents one of the promising means for the treatment of bacterial infections. In this study, we found that the natural compound fisetin could inhibit Salmonella invasion of host cells by targeting SPI-1 regulation. Fisetin treatment impaired the interaction of the regulatory protein HilD with the promoters of its target genes, thereby suppressing the expression of T3SS-1 effectors as well as structural proteins. Moreover, fisetin treatment could reduce pathology in the Salmonella murine infection model. Collectively, our results suggest that fisetin may serve as a promising lead compound for the development of anti-Salmonella drugs.

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate. Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold. Results The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compound 6f showed attractive anti-C. difficile activity. Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development. [ABSTRACT FROM AUTHOR]

Antiviral drug development is important for human health, and the emergence of novel COVID-19 variants has seriously affected human lives and safety. A bacteriophage--a bacterial virus with a small and simple structure--is an ideal experimental candidate for studying the interactions between viruses and their hosts. In this study, the effects and mechanisms of catecholamines on phages were explored, and dopamine (DA) was found to have general and efficient anti-infection effects. A clear dose-dependent effect was observed when different phages were treated with DA, with higher DA concentrations exhibiting stronger anti-phage activity. The half maximal inhibitory concentration values of DA for vB-EcoS-IME167, T4 Phage, and VMY22 were determined as 0.26, 0.12, and 0.73mgmL1, respectively. The anti-phage effect of DA increased with treatment duration. In addition, the anti-infection activities of DA against vB-EcoS-IME167, T4 Phage, and VMY22 were increased by 105, 104, and 104 folds compared to that of the control. This ability of DA was observed only in phages and not in the host bacteria. Morphological changes of phages were observed under transmission electron microscopy following their treatment with DA, and considerable changes in adsorption were confirmed via quantitative reverse transcription polymerase chain reaction. These results suggest that the anti-phage effect of DA is primarily due to the destruction of the external structure of the phage. This study, to the best of our knowledge, is the first to report the universal anti-phage infection effect of dopamine, which provides novel information regarding DA and forms a basis for further research and development of antiviral drugs. Moreover, it provides a new perspective for the research about the defense and counter-defense of bacteria and bacteriophages. [ABSTRACT FROM AUTHOR]

Poor osseointegration and postoperative bacterial infections are the main causes of clinical failure of titanium (Ti) based implants. In this study, calcium (Ca) and strontium (Sr), which have osteogenic activity, were simultaneously introduced into titanium dioxide nanotubes (TN) in order to balance the potential cytotoxicity of GL13K (Antibacterial peptides), and a multifunctional Sr, Ca and GL13K-doped TN (SrCaTN-GL13K) coating was successfully constructed. The results showed that the SrCaTN-GL13K coating exhibited good mechanical properties, hydrophilicity, corrosion resistance and bioactivity. Sr2+, Ca2+ and GL13K could be continuously released from the coating and was pH-responsive. In addition, SrCaTN-GL13K showed good antibacterial properties against E. coli and S. aureus with antibacterial rates of approximately 70.32% and 70.78%, respectively. Cellular assays showed that RAW264.7 (immune), human umbilical vein endothelial cell (HUVEC, angiogenic) and mouse embryo osteoblast precursor cell (MC3T3-E1, osteogenic) exhibited good adhesion, survival and proliferation activities on the SrCaTN-GL13K coated surface. At both gene level and protein level, expression of anti-inflammatory markers (Interleukin-10, IL-10; mannose receptor, CD206), angiogenic markers (vascular endothelial growth factor, VEGF; platelet endothelial cell adhesion molecule-1, CD31) and osteogenic markers (alkaline phosphatase, ALP; runt-related transcription factor 2, RUNX2; human collagen type I, COL1a1; osteocalcin, OCN) were significantly upregulated in SrCaTN-GL13K coating. At the cellular and molecular level, SrCaTN-GL13K possessed the ability to induce RAW264.7 towards M2 polarization and it possessed the ability to induce HUVEC tube-formation; meanwhile, it exhibited the ability to induce MC3T3-E1 towards osteogenic differentiation. In conclusion, Ti implants exhibited improved antibacterial, anti-inflammatory, angiogenic, and osteoinductive capabilities by loading Sr, Ca, and GL13K to alter TN. In this study, a multifunctional modification of Ti surface was achieved by an economical and efficient method, which provides a new idea for the design of antimicrobial implantable devices with immunomodulatory functions in the clinic. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK) has been widely used as orthopedic implants, but the poor antimicrobial and osseointegration properties hinder its advanced clinical applications. Most of the modification strategies are difficult to temporally fulfill initial broad‐spectrum antimicrobial and later pro‐osteogenic requirements for a long‐term success of implantation. N‐halamine is a kind of biofriendly antimicrobial agent, and its functional N─Cl groups could be converted into N─H groups, potentially resulting in new bioactivities. Therefore, it is supposed that N‐halamine might provide a feasible design for the dynamical integration of antimicrobial and pro‐osteogenic abilities. Herein, a new class of surface‐porous PEEK implant with an N‐halamine polymeric coating (sp‐PEEK‐NCl) is constructed by successive pore‐making, polymer grafting, and chlorination. The as‐prepared sp‐PEEK‐NCl exhibits broad‐spectrum antibacterial, antifungal, anti‐inflammatory, and pro‐osteogenic effects. More importantly, with the consumption of oxidative chlorine, the N─Cl groups in sp‐PEEK‐NCl are transformed into N─H groups with enhanced pro‐osteogenic ability, endowing sp‐PEEK‐NCl with dynamically compatible bioactivities for osseointegration in different periods after implantation. Rat implant‐associated osteomyelitis model confirms that sp‐PEEK‐NCl obviously reduces infectious bone destruction and promotes osseointegration in vivo. This work may provide a promising strategy for intelligent integration of bioactivities and valuable insight into the design of orthopedic implants in bone tissue engineering. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of medication consultation and pharmaceutical care for the treatment of stroke-associated pneumonia ( SAP ) with integrated traditional Chinese and western medicine by the clinical pharmacists, and summarize the characteristics of medication of the disease, so as to promote the clinical rational drug use. METHODS: Retrospective survey method was used to analyze the anti-infective-related medication of 87 SAP patients who were consulted by clinical pharmacists of integrated traditional Chinese and western medicine in the department of neurology of the hospital from Oct. 2020 to Oct. 2022. RESULTS: After consultation, the clinical pharmacists adjusted the anti-infective treatment regimen for 65 patients, Tongfu Xiere treatment for 21 patients, phlegm drug regimen for 42 patients, and renal function improvement regimen for 24 patients. On the basis of adjusting the anti-infective treatment regimen, the consultation pharmacist suggested strengthening the elimination of sputum, improvement of constipation and improvement of renal function from the perspective of integrated traditional Chinese and western medicine. The clinicians adopted the suggestions, and the infection indicators of the patient ( body temperature, white blood cell count, neutrophil percentage and C-reactive protein) were improved compared with those before consultation, with statistically significant difference (P<0. 05). CONCLUSIONS: Clinical pharmacists provide clinical pharmaceutical services and carry out pharmaceutical care. In addition to suggesting the selection of appropriate antibiotics, clinical pharmacists also analyzed the medication from the perspective of integrated traditional Chinese and western medicine. Tongfu Xiere treatment, phlegm elimination treatment and reducing turbidity can assist the anti-infective treatment, strengthen the control of pulmonary infection, improve the efficacy, reduce the abuse of anti-infective drugs and improve the rational application level of anti-infective drugs. [ABSTRACT FROM AUTHOR]

Biofilm formation can lead to problems in healthcare, water distribution systems, food processing and packaging, industrial manufacturing, marine industries, and sanitation. These microbial communities can proliferate on biotic or abiotic surfaces, and are responsible for human disease and decreasing production efficiency and service equipment life in many industrial fields. The formation of biofilm starts with the attachment of bacteria to the surface, followed by bacterial proliferation and maturation of the microbial community. After forming a biofilm, bacteria not resistant to antimicrobial agents in their planktonic forms can turn resistant. The antibiotic resistance of bacterial biofilm, and the association of biofilms in generating infectious diseases in humans, highlight the need for designing novel and successful antibacterial, anti-biofilm, or anti-infection materials. This paper aims to review the mechanism of biofilm formation, the impact on different industries, the interaction mechanism of nanoparticles with bacteria, and strategies to design anti-biofilm materials. Examples of designing anti-infection bio-implants, coatings, medical devices, wound dressings, and sutures are reviewed.

Abstract Background Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. Methods We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. Results Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). Conclusions Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment. Graphical Abstract

Abstract As a multifunctional fluorescent nanomaterial, carbon dots (CDs) not only have small size, stable chemical properties, excellent photoluminescence characteristics, but also exhibit good biocompatibility and low toxicity. It has attracted considerable attention in the field of nanotechnology and biological science. CDs contain abundant functional groups on the surface, which not only retain part of the properties of raw materials, but also may have new photoelectric, catalytic, biomedical, and other functions. In this review, we systematically summarize the synthesis methods, modifications, optical properties, and main biological functions of CDs in recent years. The application of functionalized modified CDs in biological detection, biological imaging, photodynamic therapy, photothermal therapy, targeted therapy, drug delivery, gene delivery, protein delivery, and other biomedical fields is introduced. The latest progress of CDs with its own biomedical function in antioxidant, anti‐pathogen, and disease treatment is summarized. Finally, we discuss some problems in the practical application of CDs and look forward to the future development trend of self‐functional CDs combined with surface modification to achieve multimodal treatment of diseases.

Biofilm formation can lead to problems in healthcare, water distribution systems, food processing and packaging, industrial manufacturing, marine industries, and sanitation. These microbial communities can proliferate on biotic or abiotic surfaces, and are responsible for human disease and decreasing production efficiency and service equipment life in many industrial fields. The formation of biofilm starts with the attachment of bacteria to the surface, followed by bacterial proliferation and maturation of the microbial community. After forming a biofilm, bacteria not resistant to antimicrobial agents in their planktonic forms can turn resistant. The antibiotic resistance of bacterial biofilm, and the association of biofilms in generating infectious diseases in humans, highlight the need for designing novel and successful antibacterial, anti-biofilm, or anti-infection materials. This paper aims to review the mechanism of biofilm formation, the impact on different industries, the interaction mechanism of nanoparticles with bacteria, and strategies to design anti-biofilm materials. Examples of designing anti-infection bio-implants, coatings, medical devices, wound dressings, and sutures are reviewed. [ABSTRACT FROM AUTHOR]

Irreversible bacterial resistance and impenetrable biofilms have rendered conventional antibiotic therapy ineffective. Nevertheless, increasing evidence has confirmed that antibiotic carbon nanodots (CDs) exhibit potent antibacterial activity. However, the complex chemical composition of antibiotic CDs, and, hence, their antibacterial mechanism, is difficult to understand. The design of new antibiotic CDs against antibacterial resistance is an urgent requirement.In this study, kanamycin‐sulfate‐derived carbon nanodots (KCDs) are found to exhibit significant antibacterial potential with the assistance of light irradiation. Systematic analysis indicates that KCDs not only retain the active structure of kanamycin but also produce five new components modified on its surface, which are shown to inhibit the activity of Staphylococcus aureus beta‐ketoacyl‐acp synthase III (FabH) through molecular docking. Furthermore, the multifunctional hydrogels (CG‐KCDs) self‐assemble into injectable, self‐healing, and antibiofilm structures through noncovalent forces between the KCDs and cationic guar gum (CG). The results indicate that under laser, CG‐KCDs irradiation exhibits enhanced antibacterial activity in vitro by damaging bacterial biofilms in a reactive oxygen species (ROS)‐dependent manner, as determined by transcriptomics. Further, the therapeutic effects of CG‐KCDs hydrogel dressings on wound healing and tissue remodeling under laser are confirmed using an in vivo wound infection model. These results validate the potential of KCDs as efficient antibacterial agents to replace antibiotics as an anti‐infective strategy. [ABSTRACT FROM AUTHOR]

Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair. [ABSTRACT FROM AUTHOR]

Fibrous biomaterials are widely used in the design and fabrication of antibacterial wound dressings. Two strategies are used to make anti-infective dressings: antibacterial and probiotic therapies, which have potential biotoxicity and other side-effects. Herein, we report a new strategy for fabricating wound dressings to combat infection. Poly(4-methyl-1-pentene) (PMP) fabric can remove bacteria from infectious wounds through dressing changes based on its efficient bacterial adhesion. The maximum adhered count of S. aureus and E. coli on the PMP fabric was 1.63 × 106 CFU/cm2 and 4.77 × 105 CFU/cm2, respectively. In addition, the PMP fabric could inhibit the twitching motility of bacteria, which is beneficial for inhibiting infection. The ability of the PMP fabric to accelerate wound healing was demonstrated in vivo in a rat wound model. After treatment with the PMP fabric dressing, pathogenic bacteria in the wound were removed through dressing change; therefore, the wound exhibited better healing speed than when the commercial dressing was used. The low bacterial concentration effectively stimulated the expression of growth factors and suppressed wound inflammation, thereby accelerating wound healing. PMP fabric has three advantages: (1) it has been approved for use in clinical treatment by the Food and Drug Administration; (2) no antibacterial agent or probiotics were used; (3) the fabric could be manufactured through an industrial production process. These results indicate that the new strategy can be used in the design of new-generation wound dressings for antibacterial applications. [ABSTRACT FROM AUTHOR]

Pullorum disease, caused by Salmonella Pullorum (S. Pullorum), is one of the most serious infectious diseases in the poultry industry. Flos populi is traditionally used in Eastern Asian countries to treat various intestinal diseases. However, the anti-infection mechanism of Flos populi is not very clear. In this study, we evaluated the anti-infective effects on S. Pullorum of Flos populi aqueous extract (FPAE) in chickens. FPAE significantly reduced S. Pullorum growth in vitro. At the cellular level, FPAE reduced S. Pullorum adhesion and invasion on DF-1 cells but did not affect its intracellular survival or replication in macrophages. Further investigation revealed that FPAE inhibited the transcription of T3SS-1 genes, which is the main virulence factor that mediates S. Pullorum adhesion and invasion in host cells. The results suggest that the anti-infective effect of FPAE likely occurs through the inhibition of S. Pullorum T3SS-1, thereby impairing its ability to adhere to and invade cells. Further, we evaluated its therapeutic effect on animal models (Jianghan domestic chickens) and found that FPAE reduced the bacterial loads in organs and decreased the mortality and weight loss of infected chickens. Our findings provide novel insights into the potential development of FPAE against S. Pullorum as an effective anti-virulence therapeutic substitute for antibiotics. [ABSTRACT FROM AUTHOR]

The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] It is widely regarded that antimicrobial peptides (AMPs) kill bacteria by physically disrupting microbial membranes and causing cytoplasmic leakage, but it remains unclear how AMPs disrupt the outer membrane (OM) of Gram-negative bacteria (GNB) and then compromise the inner membrane. We hypothesise that different AMPs impose different structural disruptions, with direct implications to their antimicrobial efficacies. The antimicrobial activities of three typical AMPs, including the designed short AMP, G 3 , and two natural AMPs, melittin and LL37, against E. coli and their haemolytic activities were studied. Lipopolysaccharide (LPS) and anionic di-palmitoyl phosphatidyl glycerol (DPPG) monolayer models were constructed to mimic the outer membrane and inner membrane leaflets of Gram-negative bacteria. The binding and penetration of AMPs to the model lipid monolayers were systematically studied by neutron reflection via multiple H/D contrast variations. G 3 has relatively high antimicrobial activity, low cytotoxicity, and high proteolytic stability, whilst melittin has significant haemolysis and LL37 has weaker antimicrobial activity. G 3 could rapidly lyse LPS and DPPG monolayers within 10–20 min. In contrast, melittin was highly active against the LPS membrane, but the dynamic process lasted up to 80 min, with excessive stacking in the OM. LL37 caused rather weak destruction to LPS and DPPG monolayers, leading to massive adsorption on the membrane surface without penetrating the lipid tail region. These findings demonstrate that the rationally designed AMP G 3 was well optimised to impose most effective destruction to bacterial membranes, consistent with its highest bactericidal activity. These different interfacial structural features associated with AMP binding shed light on the future development of active and biocompatible AMPs for infection and wound treatments. [ABSTRACT FROM AUTHOR]

Postoperative bacterial infection and poor osseointegration with surrounding bone tissue are not only the critical causes of implant failure but also the major challenges in clinical application. Hereby, Titania (TiO2) microporous/nanofiber coating was firstly prepared on the surface of titanium (Ti) material by alkali-heat treatment process, and strontium (Sr)-doped coating (TS) was then prepared by hydrothermal synthesis. Finally, polydopamine-assisted co-deposition technology was utilized to deposit vancomycin (Van) onto TS surface (TSV), thus obtaining a medical composite coating with antibacterial property and improved osseointegration ability. According to antibacterial test, TSV has not only a 99.99% killing effect on methicillin-resistant Staphylococcus aureus (MRSA), but also a good anti-biofilm ability. The cell experiments showed that TSV could enhance the adhesion and proliferation of osteoblasts. Compared with pure Ti and TS, TSV induces the formation of bone apatite in simulated body fluid (SBF) test quickly, indicating that the coating has good biological activity. According to histopathological observation and bone morphology analysis, TSV showed highly effective infection prevention and excellent osteointegration in vivo. These test results suggested that it is feasible to prevent implant-associated infection and promote osseointegration by functionalization of the implant, so as to provide a fresh direction for clinical research.

Graphene-based nanomaterials (GBNMs) has been thoroughly investigated and extensively used in many biomedical fields, especially cancer therapy and bacteria-induced infectious diseases treatment, which have attracted more and more attentions due to the improved therapeutic efficacy and reduced reverse effect. GBNMs, as classic two-dimensional (2D) nanomaterials, have unique structure and excellent physicochemical properties, exhibiting tremendous potential in cancer therapy and bacteria-induced infectious diseases treatment. In this review, we first introduced the recent advances in development of GBNMs and GBNMs-based treatment strategies for cancer, including photothermal therapy (PTT), photodynamic therapy (PDT) and multiple combination therapies. Then, we surveyed the research progress of applications of GBNMs in anti-infection such as antimicrobial resistance, wound healing and removal of biofilm. The mechanism of GBNMs was also expounded. Finally, we concluded and discussed the advantages, challenges/limitations and perspective about the development of GBNMs and GBNMs-based therapies. Collectively, we think that GBNMs could be potential in clinic to promote the improvement of cancer therapy and infections treatment.

Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore‐forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface‐associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY‐mediated cell damage and reduced SrtA‐mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony‐forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF‐α, IL‐6 and IL‐1β in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug‐resistant bacteria. Here, an in situ‐formed biotherapeutic gel that controls multidrug‐resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene‐polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities‐based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria‐derived xenograft infection models, as well as in patient‐derived multidrug‐resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad‐spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug‐resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics of phage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment. The data showed that phage had a good therapeutic effect on drug-resistant bacteria in veterinary fields, as well as in the clinical treatment of humans. However, we need to take more consideration of the narrow lysis spectrum, the immune response, the issues of storage, and the pharmacokinetics of phages. Due to the particularity of bacteriophage as a bacterial virus, there is no unified standard or regulation for the use of bacteriophage in the world at present, which hinders the application of bacteriophage as a substitute for antibiotic biological products. We aimed to highlight the rapidly advancing field of phage therapy as well as the challenges that China faces in reducing its reliance on antibiotics. [ABSTRACT FROM AUTHOR]