A Smart Bacteria-Capture-Killing Vector for Effectively Treating Osteomyelitis Through Synergy Under Microwave Therapy.

Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Associations between Plasma Essential Metals Levels and the Risks of All-Cause Mortality and Cardiovascular Disease Mortality among Individuals with Type 2 Diabetes.

Epidemiological evidence regarding the possible link between multiple essential metals levels and all-cause mortality and cardiovascular disease (CVD) mortality among type 2 diabetes (T2D) patients is sparse. Here, we aimed to evaluate the longitudinal associations between 11 essential metals levels in plasma and all-cause mortality and CVD mortality among T2D patients. Our study included 5278 T2D patients from the Dongfeng-Tongji cohort. LASSO penalized regression analysis was used to select the all-cause and CVD mortality-associated metals from 11 essential metals (iron, copper, zinc, selenium, manganese, molybdenum, vanadium, cobalt, chromium, nickel, and tin) measured in plasma. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up of 9.8 years, 890 deaths were documented, including 312 deaths of CVD. LASSO regression models and the multiple-metals model revealed that plasma iron and selenium were negatively associated with all-cause mortality (HR: 0.83; 95%CI: 0.70, 0.98; HR: 0.60; 95%CI: 0.46, 0.77), whereas copper was positively associated with all-cause mortality (HR: 1.60; 95%CI: 1.30, 1.97). Only plasma iron has been significantly associated with decreased risk of CVD mortality (HR: 0.61; 95%CI: 0.49, 0.78). The dose-response curves for the association between copper levels and all-cause mortality followed a J shape (Pfor nonlinear = 0.01). Our study highlights the close relationships between essential metals elements (iron, selenium, and copper) and all-cause and CVD mortality among diabetic patients.

CRISPR/Cas9 Mutant Rice Ospmei12 Involved in Growth, Cell Wall Development, and Response to Phytohormone and Heavy Metal Stress.

Pectin is one of the constituents of the cell wall, distributed in the primary cell wall and middle lamella, affecting the rheological properties and the cell wall stickiness. Pectin methylesterase (PME) and pectin methylesterase inhibitor (PMEI) are the most important factors for modifying methyl esterification. In this study, 45 PMEI genes from rice (Oryza sativa L.) were screened by bioinformatics tools, and their structure, motifs, cis-acting elements in the promoter region, chromosomal distribution, gene duplication, and phylogenetic relationship were analyzed. Furthermore, CRISPR/Cas9 was used to edit the OsPMEI12 (LOC_Os03G01020) and two mutant pmei12 lines were obtained to explore the functions of OsPMEI in plant growth and development, and under cadmium (Cd) stress. Compared to wild type (WT) Nipponbare, the second inverted internodes of the mutant plants shortened significantly, resulting in the reduction in plant height at mature stage. The seed setting rate, and fresh and dry weights of the mutants were also decreased in mutant plants. In addition, the pectin methylation of pmei12 lines is decreased as expected, and the pectin content of the cell wall increased at both seedling and maturity stages; however, the cellulose and hemicellulose increased only at seedling stage. Interestingly, the growth of the pmei12 lines was better than the WT in both normal conditions and under two phytohormone (GA3 and NAA) treatments at seedling stage. Under Cd stress, the fresh and dry weights were increased in pmei12 lines. These results indicated that OsPMEI12 was involved in the regulation of methyl esterification during growth, affected cell wall composition and agronomic traits, and might play an important role in responses to phytohormones and stress.

Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.

Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming •O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.

Microwave assisted antibacterial action of Garcinia nanoparticles on Gram-negative bacteria.

Owing to the existence of the outer membrane barrier, most antibacterial agents cannot penetrate Gram-negative bacteria and are ineffective. Here, we report a general method for narrow-spectrum antibacterial Garcinia nanoparticles that can only be effective to kill Gram-positive bacteria, to effectively eliminate Gram-negative bacteria by creating transient nanopores in bacterial outer membrane to induce drug entry under microwaves assistance. In vitro, under 15 min of microwaves irradiation, the antibacterial efficiency of Garcinia nanoparticles against Escherichia coli can be enhanced from 6.73% to 99.48%. In vivo, MV-assisted GNs can effectively cure mice with bacterial pneumonia. The combination of molecular dynamics simulation and experimental results reveal that the robust anti-E. coli effectiveness of Garcinia nanoparticles is attributed to the synergy of Garcinia nanoparticles and microwaves. This work presents a strategy for effectively treating both Gram-negative and Gram-positive bacteria co-infected pneumonia using herbal medicine nanoparticles with MV assistance as an exogenous antibacterial auxiliary.

Identification of Visual Imagery by Electroencephalography Based on Empirical Mode Decomposition and an Autoregressive Model.

The traditional imagery task for brain-computer interfaces (BCIs) consists of motor imagery (MI) in which subjects are instructed to imagine moving certain parts of their body. This kind of imagery task is difficult for subjects. In this study, we used a less studied yet more easily performed type of mental imagery-visual imagery (VI)-in which subjects are instructed to visualize a picture in their brain to implement a BCI. In this study, 18 subjects were recruited and instructed to observe one of two visual-cued pictures (one was static, while the other was moving) and then imagine the cued picture in each trial. Simultaneously, electroencephalography (EEG) signals were collected. Hilbert-Huang Transform (HHT), autoregressive (AR) models, and a combination of empirical mode decomposition (EMD) and AR were used to extract features, respectively. A support vector machine (SVM) was used to classify the two kinds of VI tasks. The average, highest, and lowest classification accuracies of HHT were 68.14 ± 3.06%, 78.33%, and 53.3%, respectively. The values of the AR model were 56.29 ± 2.73%, 71.67%, and 30%, respectively. The values obtained by the combination of the EMD and the AR model were 78.40 ± 2.07%, 87%, and 48.33%, respectively. The results indicate that multiple VI tasks were separable based on EEG and that the combination of EMD and an AR model used in VI feature extraction was better than an HHT or AR model alone. Our work may provide ideas for the construction of a new online VI-BCI.

Photo-Sono Interfacial Engineering Exciting the Intrinsic Property of Herbal Nanomedicine for Rapid Broad-Spectrum Bacteria Killing.

Large doses and long duration are often required for herbal medicines to kill bacteria effectively. Herein, a photoacoustic interfacial engineering strategy was utilized to endow curcumin (Cur, a kind of herbal medicine) with rapid and highly effective bacteria-killing efficacy, in which Cur was combined with CuS to form a hybrid material of CuS/Cur with tight contact through in situ nucleation and growth on the petaloid CuS surface. Due to the different work functions of CuS and Cur, the interfacial electrons were redistributed, i.e., a large number of electrons gathered on the side of CuS. In contrast, the holes gathered on the side of Cur after contact. An internal electric field was formed to drive the excited electrons to transfer from CuS to Cur, thus enhancing the separation of electron-hole pairs. Besides exerting the drug nature of Cur itself, the CuS/Cur hybrid also had photo-sono responsive ability, which endowed the hybrid with photothermal, photodynamic, and sonodynamic effects. Therefore, this Cur-based hybrid killed 99.56% of Staphylococcus aureus and 99.48% of Escherichia coli under 808 nm near-infrared light irradiation and ultrasound successively for 15 min, which was ascribed to the synergy of ROS, hyperthermia, and released Cu2+ together with the drug properties of Cur. This work provides a strategy to enhance the therapeutic effects of herbal medicines against pathogenic bacterial infections by exciting the intrinsic properties of herbal medicines as materials through a photo-sono interfacial engineering strategy.

The recent progress on metal-organic frameworks for phototherapy.

Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.

Ultrasonic Interfacial Engineering of Red Phosphorous-Metal for Eradicating MRSA Infection Effectively.

Sonodynamic therapy (SDT) is considered to be a potential treatment for various diseases including cancers and bacterial infections due to its deep penetration ability and biosafety, but its SDT efficiency is limited by the hypoxia environment of deep tissues. This study proposes creating a potential solution, sonothermal therapy, by developing the ultrasonic interfacial engineering of metal-red phosphorus (RP), which has an obviously improved sonothermal ability of more than 20 °C elevation under 25 min of continuous ultrasound (US) excitation as compared to metal alone. The underlying mechanism is that the mechanical energy of the US activates the motion of the interfacial electrons. US-induced electron motion in the RP can efficiently transfer the US energy into phonons in the forms of heat and lattice vibrations, resulting in a stronger US absorption of metal-RP. Unlike the nonspecific heating of the cavitation effect induced by US, titanium-RP can be heated in situ when the US penetrates through 2.5 cm of pork tissue. In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.

Ag3PO4 decorated black urchin-like defective TiO2 for rapid and long-term bacteria-killing under visible light.

Both phototherapy via photocatalysts and physical puncture by artificial nanostructures are promising substitutes for antibiotics when treating drug-resistant bacterial infectious diseases. However, the photodynamic therapeutic efficacy of photocatalysts is seriously restricted by the rapid recombination of photogenerated electron-hole pairs. Meanwhile, the nanostructures of physical puncture are limited to two-dimensional (2D) platforms, and they cannot be fully used yet. Thus, this research developed a synergistic system of Ag3PO4 nanoparticles (NPs), decorated with black urchin-like defective TiO2 (BU-TiO2-X/Ag3PO4). These NPs had a decreased bandgap compared to BU-TiO2-X, and BU-TiO2-X/Ag3PO4 (3:1) exhibited the lowest bandgap and the highest separation efficiency for photogenerated electron-hole pairs. After combination with BU-TiO2-X, the photostability of Ag3PO4 improved because the oxygen vacancy of BU-TiO2-X retards the reduction of Ag+ in Ag3PO4 into Ag0, thus reducing its toxicity. In addition, the nanospikes on the surface of BU-TiO2-X can, from all directions, physically puncture bacterial cells, thus assisting the hybrid's photodynamic therapeutic effects, alongside the small amount of Ag+ released from Ag3PO4. This achieves synergy, endowing the hybrid with high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against Escherichia coli and Staphylococcus aureus, respectively, after light irradiation for 20 min followed by darkness for 12 h. It is anticipated that these findings may bring new insight for developing synergistic treatment strategies against bacterial infectious diseases or pathogenic bacterial polluted environments.

Photoelectrons Mediating Angiogenesis and Immunotherapy through Heterojunction Film for Noninvasive Disinfection.

A light-inspired hydroxyapatite (Hap)/nitrogen-doped carbon dots (NCDs) modified graphene oxide (GO) heterojunction film is developed, which shows a promoted separation of interfacial electrons and holes and an inhibited recombination efficiency via hole depletion. The metabolism of bacteria on this film is significantly inhibited under light irradiation, due to the enhanced photocatalytic and photothermal effects. In addition, the electron transfer from the plasmonic membrane to the GO/NCD/Hap film further inhibits the adenosine triphosphate process of bacteria, thus leading to the synergetic antibacterial efficacy. Meanwhile, the electron transfer between film and cell membrane induces the Ca2+ flow after irradiation, which can promote the migration and proliferation of cells and alkaline phosphatase enhancement, thus favoring the tissue reconstruction. An in vivo test discloses that the vascular injury repair is achieved through the Ca2+-activated PLCγ1/ERK pathway, identified by the enhanced CD31 expression. Moreover, the increased CD4+/CD8+ lymphocytes are ameliorative by activating the PI3K/P-AKT pathway. Consequently, the electron transfer boosts the synergic photodynamic and photothermal therapeutic effects for bacterial infection by Ca2+ flow for immunotherapy. This mild phototherapy approach with GO/NCDs/Hap, which can simultaneously repair injured vessels and relieve inflammation reactions, will increase the clinical application of noninvasive phototherapy in the near future.

Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing.

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.

Near-Infrared Light Triggered Phototherapy and Immunotherapy for Elimination of Methicillin-Resistant Staphylococcus aureus Biofilm Infection on Bone Implant.

Clinically, methicillin-resistant Staphylococcus aureus (MRSA) biofilm infection inevitably induces the failure of bone implants. Herein, a hydrophilic and viscous hydrogel of poly(vinyl alcohol) modified with chitosan, polydopamine, and NO release donor was formed on a red phosphorus nanofilm deposited on a titanium implant (Ti-RP/PCP/RSNO). Under the irradiation of near-infrared light (NIR), peroxynitrite (•ONOO-) was formed by the reaction between the released NO and superoxide (•O2-) produced by the RP nanofilm. Specifically, we revealed the antibacterial mechanism of the ONOO- against the MRSA biofilm. In addition, osteogenic differentiation was promoted and inflammatory polarization was regulated by the released NO without NIR irradiation through upregulating the expression of Opn and Ocn genes and TNF-α. The MRSA biofilm was synergistically eradicated by •ONOO-, hyperthermia, and •O2- under NIR irradiation as well as the immunoreaction of the M1 polarization. The in vivo results also confirmed the excellent osteogenesis and biofilm eradication by released NO from the RP/PCP/RSNO system under NIR irradiation, indicating the noninvasive tissue reconstruction of MRSA-infected tissues through phototherapy and immunotherapy.

Zn2+-assisted photothermal therapy for rapid bacteria-killing using biodegradable humic acid encapsulated MOFs.

Bacterial infection is seriously threatening human health all over the world, especially with the emergence of increasing drug-fast bacteria. It is urgent to develop a drug-free strategy to kill bacteria rapidly and efficiently. In this work, humic acid (HuA) encapsulated zeolitic imidazole framework-8 (ZIF-8) (HuA@ZIF-8) nanocomposites are synthesized by the in-situ growth of ZIF-8 on the surface of polyvinylpyrrolidone (PVP)-modified HuA. The synthesized nanocomposites possesses good photothermal effects, i.e., the temperature increased to 59.4 °C under the particle concentration of 1000 µg/mL with 10 min NIR irradiation. In addition, NIR irradiation can also control the release of Zn2+ from the composites. The good photothermal effects originate from HuA that can effectively absorb NIR light. The controlled release of Zn2+ is ascribed to the induced-dissociation of ZIF-8 under NIR light irradiation. The synergistic action of photothermal therapy and release of zinc ions contributes to the excellent antibacterial efficiency of HuA@ZIF-8 within a short time, i.e. 99.59 % and 99.37 % against Staphylococcus aureus and Escherichia coli with 20 min NIR irradiation, respectively. This work provides a promising strategy to develop a light-responsive platform with good biodegradability and low cost for rapid and effective sterilization.

Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds.

Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)1 and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder2. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract3. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.

Association between exposure to arsenic, nickel, cadmium, selenium, and zinc and fasting blood glucose levels.

Associations between single metal and fasting blood glucose (FBG) levels have been reported in previous studies. However, the association between multi-metals exposure and FBG level are little known. To assess the joints of arsenic (As), nickel (Ni), cadmium (Cd), selenium (Se), and zinc (Zn) co-exposure on FBG levels, Bayesian kernel machine regression (BKMR) statistical method was used to estimate the potential joint associations between As, Ni, Cd, Se, and Zn co-exposure and FBG levels among 1478 community-based Chinese adults from two counties, Shimen (n = 696) and Huayuan (n = 782), with different exposure profiles in Hunan province of China. The metals levels were measured in spot urine (As, Ni, and Cd) and plasma (Se and Zn) using inductively coupled plasma-mass spectrometry, respectively. The exposure levels of all the five metals were significantly higher in Shimen area (median: As = 57.76 µg/L, Cd = 2.75 µg/L, Ni = 2.73 µg/L, Se = 112.67 µg/L, Zn = 905.68 µg/L) than those in Huayuan area (As = 41.14 µg/L, Cd = 2.22 µg/L, Ni = 1.88 µg/L, Se = 65.59 µg/L, Zn = 819.18 µg/L). The BKMR analyses showed a significantly positive over-all effect of the five metals on FBG levels when metals concentrations were all above the 50th percentile while a statistically negative over-all effect when metals concentrations were all under the 50th percentile in Shimen area. However, a totally opposite over-all effect of the mixture of the five metals on FBG levels was found in Huayuan area. BKMR also revealed a non-linear exposure-effect of Zn on FBG levels in Huayuan area. In addition, interaction effects of As and Se on FBG level were observed. The relationship between single or combined metals exposure and FBG was different against different exposure profiles. Potential interaction effects of As and Se on FBG levels may exist.

Highly Effective and Noninvasive Near-Infrared Eradication of a Staphylococcus aureus Biofilm on Implants by a Photoresponsive Coating within 20 Min.

Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine-glycine-aspartic acid-cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron-sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near-infrared (NIR, λ = 700-1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.

Lysozyme-Assisted Photothermal Eradication of Methicillin-Resistant Staphylococcus aureus Infection and Accelerated Tissue Repair with Natural Melanosome Nanostructures.

Patients often face the challenge of antibiotic-resistant bacterial infections and lengthy tissue reconstruction after surgery. Herein, human hair-melanosome derivatives (HHMs), comprising keratins and melanins, are developed using a simple "low-temperature alkali heat" method for potentially personalized therapy. The mulberry-shaped HHMs have an average width of ∼270 nm and an average length of ∼700 nm, and the negatively charged HHMs can absorb positively charged Lysozyme (Lyso) to form the HHMs-Lyso composites through electrostatic interaction. These naturally derived biodegradable nanostructures act as exogenous killers to eliminate methicillin-resistant Staphylococcus aureus (MRSA) infection with a high antibacterial efficacy (97.19 ± 2.39%) by synergistic action of photothermy and "Lyso-assisted anti-infection" in vivo. Additionally, HHMs also serve as endogenous regulators of collagen alpha chain proteins through the "protein digestion and absorption" signaling pathway to promote tissue reconstruction, which was confirmed by quantitative proteomic analysis in vivo. Notably, the 13 upregulated collagen alpha chain proteins in the extracellular matrix (ECM) after HHMs treatment demonstrated that keratin from HHMs in collagen-dependent regulatory processes serves as a notable contributor to augmented wound closure. The current paradigm of natural material-tissue interaction regulates the cell-ECM interaction by targeting cell signaling pathways to accelerate tissue repair. This work may provide insight into the protein-level pathways and the potential mechanisms involved in tissue repair.