Three-Pronged Flower-like Nanoplatforms for the Photothermal/Photodynamic/Quaternary Ammonium Salt Synergistic Antibacterial Method and Bioimaging.

Bacterial infections caused by pathogenic bacteria are extremely threatening to human health. Currently, the treatment of bacterial infections relies heavily on antibiotics, leading to a high incidence of antibiotic abuse. Bacterial resistance appeared along with the misuse of antibiotics that produced growing harm to human beings. Therefore, a cutting-edge strategy for treating bacterial infections is indeed needed. Here we prepared QCuRCDs@BMoS2 nanocomposites (QBs) for an efficient bacterial trapping and triple quaternary ammonium salt/photothermal/photodynamic bactericidal method. Copper-doped carbon quantum dots were first prepared by using a solvothermal method, modified with quaternary ammonium salts, and then combined with grafted MoS2 nanoflowers. The long alkyl chains of QBs and the sharp surface of MoS2 facilitate the destruction of bacterial structures, while the electrostatic adsorption binds closely to bacteria, shortening the bactericidal distance of the reactive oxygen species (ROS). Moreover, the excellent photothermal performance under 808 nm irradiation in the near-infrared (NIR) region and deep penetrating heat can accelerate oxidative stress and achieve a multisynergistic bactericidal purpose. Consequently, QBs with ideal antibacterial properties and inherent brightness hold great promise in the biomedical field.

Codelivery of TRAIL and Mitomycin C via Liposomes Shows Improved Antitumor Effect on TRAIL-Resistant Tumors.

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.

Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer.

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

Pangenome obtained by long-read sequencing of 11 genomes reveal hidden functional structural variants in pigs.

Long-read sequencing (LRS) facilitates both the genome assembly and the discovery of structural variants (SVs). Here, we built a graph-based pig pangenome by incorporating 11 LRS genomes with an average of 94.01% BUSCO completeness score, revealing 206-Mb novel sequences. We discovered 183,352 nonredundant SVs (63% novel), representing 12.12% of the reference genome. By genotyping SVs in an additional 196 short-read sequencing samples, we identified thousands of population stratified SVs. Particularly, we detected 7,568 Tibetan specific SVs, some of which demonstrate significant population differentiation between Tibetan and low-altitude pigs, which might be associated with the high-altitude hypoxia adaptation in Tibetan pigs. Further integrating functional genomic data, the most promising candidate genes within the SVs that might contribute to the high-altitude hypoxia adaptation were discovered. Overall, our study generates a benchmark pangenome resource for illustrating the important roles of SVs in adaptive evolution, domestication, and genetic improvement of agronomic traits in pigs.

Multifunctional Integrated Superhydrophobic Coatings with Unique Fluorescence and Micro/Micro/Nano-Hierarchical Structures Enabled by In Situ Self-Assembly.

Conferring versatility to superhydrophobic materials is extremely desirable to advance their utility. Herein, we have developed a superhydrophobic material with montmorillonite as microskeleton supports and in situ grown ZIF-8 nanoparticles and loaded them with newly developed fluorescent carbon dots. In situ growth of the ZIF-8 on OMMT constructs a dense nanoscale rough structure and meanwhile self-assembly generates abundant microporous, thus forming unique hierarchical microporous/microsheet/nanoparticle tri-tier micro and nano structures. Then the multifunctional superhydrophobic coating is fabricated by a facile spraying technique using polydimethylsiloxane (PDMS) as a multifunctional polymer binder. The PDMS/RB-CDs/ZIF-8@OMMT exhibits superhydrophobicity with a water contact angle of 164.7° and a water sliding angle of 1.4°, which also possesses good self-cleaning performance. Moreover, novel carbon dots are developed in this work which can confer unique fluorescent properties and photothermal properties to materials. Fluorescence characterization reveals the multiple emission peaks among 300-800 nm and excitation wavelength dependence and independence. Photothermal experiments unveil an efficient light-to-heat conversion caused by the light traps and absorption wavelengths associated with photothermal heating. Benefiting from the dense microporous/microsheet/nanoparticle structures, the superhydrophobicity is still maintained after 120 cycles of abrasion. Moreover, electrochemical impedance spectroscopy (EIS) reveals a significant increase in impedance, which is associated with excellent corrosion resistance. The superhydrophobic coating also exhibits superior UV resistance and good thermal stability. Multifunctional fluorescent superhydrophobic materials will enable the development of various and potential applications in different fields.

The clinical effect of WeChat-based MUST education model on patients with chronic heart failure.

OBJECTIVE: To explore the effect of WeChat-based MUST nursing intervention on self-care ability and quality of life in patients with chronic heart failure. METHOD: Convenient sampling was used to select CHF patients who received treatment in XX Hospital from January 1, 2020, to December 30, 2020, as the study subjects and was divided into the experimental group (n = 60) and the control group (n = 60) according to the random number table. The experimental group used the WeChat-based MUST nursing intervention, and the control group used the routine education and follow-up model. Cardiac function parameters, self-care ability, and other indicators were compared between the two groups before and after nursing. The clinical effect of two groups was evaluated. RESULTS: After the nursing intervention, LVEF levels were increased to different extents and NT-proBNP was decreased to different extents in both groups. LVEF level in the experimental group was higher than that in the control group, and the NT-proBNP level in the experimental group was lower than that in the control group. After the nursing intervention, the self-care ability and quality of life of the two groups were increased to varying degrees. Self-care ability was higher in the experimental group than in the control group, and quality of life was higher in the experimental group than in the control group. CONCLUSION: The WeChat-based MUST nursing intervention model in patients with chronic heart failure, compared with the conventional cardiology nursing model, can effectively improve the self-care ability of patients, improve the knowledge level and quality of life of patients with heart failure, and reduce the readmission rate.

Hydrophilic Nanocomposite Films with a Fence-Structure-Induced Labyrinth Effect for Greenhouse Cooling and Light Enhancement.

In this paper, we reported a new kind of cooling and light-enhanced hydrophilic nanocomposite film (PE/JW-0.8%) with low-density polyethylene (LDPE) as the substrate. The wetting, photophysical, and mechanical properties of PE/JW-0.8% were tested. The emission band of the fluorescence centers at 420 nm, which is perfectly consistent with the absorption spectrum of plant photosynthesis. In addition, light can be scattered by PE/JW-0.8% to achieve a larger light distribution area. PE/JW-0.8% showed a good durability of hydrophilicity in the water rinsing test. Meanwhile, the elongation at the break of the film was significantly increased. Benefiting from the fence structure induced labyrinth effect, a maximum reduction of 6.7 °C in temperature monitoring for PE/JW-0.8% was observed in the detailed field experiments. Light intensity monitoring showed that light intensity in PE/JW-0.8% increased by a maximum of 57.1% compared to PE/LH. In the biological quality analysis of melon, it was found that the soluble sugar, soluble solid, and vitamin C content of melon increased by 13.34, 22.96, and 50.95%, respectively. In conclusion, these results confirm that PE/JW-0.8% has great application potential in the field of facility agriculture, buildings, and photovoltaic modules.

An investigation of the role of transition metal ions impurities in CdO: Local structure and electronic properties.

According to the high-order perturbation formulae of 3d5 (Mn2+ ) and 3d9 (Cu2+ ) ions in octahedron, the local structures and electron paramagnetic resonance (EPR) parameters (g factors and hyperfine structure constants A) for Cu2+ and Mn2+ in CdO are theoretically studied in a consistent way. Due to the Jahn-Teller effect, both the substituted sites of Cu2+ and Mn2+ show the tetragonally elongated distortion with different elongation τ. Meanwhile, the crystal field and covalency around doped Cu2+ and Mn2+ are obtained, which can account for the electronic properties in doped CdO. In order to make further investigation of the potential optical and electrical properties, the band structure and density of states (DOS) of pure and transition metal ions (TMs) doped CdO are comparably calculated through density functional theory (DFT). The results show that the band gap of Mn2+ - and Cu2+ -doped CdO can be effectively reduced, due to the improved covalency between the central ions and ligand ions.

An Optimally Designed Engineering Exosome-Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing.

Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno-engineered exosome (PCOF@E-Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E-Exo is collected from TNF-α-treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti-inflammatory M2 macrophage polarization, but also stabilizes hypoxia-inducible factor-1α (HIF-1α). More importantly, the PCOF@E-Exo exhibits intriguing bactericide capabilities toward Gram-negative, Gram-positive, and drug-resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.

A multifunctional carbon dot-based nanoplatform for bioimaging and quaternary ammonium salt/photothermal synergistic antibacterial therapy.

The emergence of drug resistance and superbugs poses a devastating threat to public health and can even lead to death. Thus, it is significant to develop a novel antibacterial agent to combat bacterial infections. Herein, we developed quaternary ammonium salt (QAS) modified near-infrared carbon dots (RCDs-C35), which possesses synergistic antibacterial performance under 808 nm irradiation. This nanocomposite exhibits excellent photothermal performance and the photothermal conversion efficiency (PCE) could reach 35%. Generally speaking, the bacterial membrane sensitivity to hyperthermia would be enhanced after QAS caused the initial damage, and thus it can more easily cause bacterial inactivation after irradiation. In vitro and in vivo experiments indicated that the RCDs-C35 exhibit excellent biocompatibility, predominant synergistic antibacterial performance, and the capability of promoting wound healing. The antibacterial ratio against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) could reach 99.5% and 99.8%, respectively, after 808 nm irradiation. Additionally, the cellular imaging indicated that the RCDs-C35 could be used as a fluorescent probe in bioimaging. Therefore, RCDs-C35 with synergistic antibacterial performance and inherent luminescence possess great potential for application in the biomedical field.

Silica-supported near-infrared carbon dots and bicarbonate nanoplatform for triple synergistic sterilization and wound healing promotion therapy.

Widespread bacterial infection and the emergence of antibiotic resistance exhibit an increasing threat to public health. Additionally, chronic wounds caused by bacterial infection have become a major challenge and threat in medical. Therefore, it is of great significance to explore effective and safe nanomaterials which possess antibacterial and wound healing promotion performance. Herein, we developed silica-supported near-infrared carbon dots (QPCuRC@MSiO2) and bicarbonate (BC) nanoplatform (BC/QPCuRC@MSiO2@PDA), which possess triple synergistic antibacterial including quaternary ammonium compounds (QACs), photothermal therapy (PTT), and photodynamic therapy (PDT). Meanwhile, the nanoplatform realized the controlled release of CO2 in situ triggered by 808 nm laser irradiation for wound healing. In vitro and in vivo antibacterial assays displayed that the BC/QPCuRC@MSiO2@PDA possess excellent antibacterial property, the antibacterial rate up to 99.6% and 99.99% to Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. Wound healing evaluation proved that suitable release of CO2 could promote the process of infected wound healing, and the wound healing rate up to 100% after treatment for 14 days. Additionally, the cellular imaging experiment revealed that the BC/QPCuRC@MSiO2@PDA could be considered as fluorescence probe. Together, these results demonstrated that the BC/QPCuRC@MSiO2@PDA have great potential in biomedical field.

Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection.

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

MoO3-x nanosheets-based platform for single NIR laser induced efficient PDT/PTT of cancer.

Traditional combination therapy of photodynamic therapy (PDT) and photothermal therapy (PTT) is limited in the field of clinical cancer therapy due to activation by light with separate wavelengths, insufficient O2 supply, antioxidant ability of glutathione (GSH) in tumor cell, and low penetration depth of light. Here, a multifunctional nanoplatform composed of MoO3-x nanosheets, Ag nanocubes, and MnO2 nanoparticles was developed to overcome these drawbacks. For this nanoplatform, hyperthermia and reactive oxygen species (ROS) were simultaneously generated under single 808 nm near-infrared (NIR) light irradiation. Once this nanoplatform accumulated in the tumor region, GSH was depleted by MnO2 and intracellular H2O2 was catalyzed by MnO2 to produce O2 to relieve hypoxia. Ultrasound (US) imaging confirmed in-situ O2 generation. Magnetic resonance (MR) imaging, photoacoustic (PA) imaging, and fluorescence imaging were used to monitor in vivo biodistribution of nanomaterials. This provides a paradigm to rationally design a single NIR laser induced multimodal imaging-guided efficient PDT/PTT cancer strategy.

Multiple-Dimensionally Controllable Nucleation Sites of Two-Dimensional WS2/Bi2Se3 Heterojunctions Based on Vapor Growth.

Two-dimensional (2D) heterojunctions have attracted great attention due to their excellent optoelectronic properties. Until now, precisely controlling the nucleation density and stacking area of 2D heterojunctions has been of critical importance but still a huge challenge. It hampers the progress of controlled growth of 2D heterojunctions for optoelectronic devices because the potential relation between numerous growth parameters and nucleation density is always poorly understood. Herein, by cooperatively controlling three parameters (substrate temperature, gas flow rate, and precursor concentration) in modified vapor deposition growth, the nucleation density and stacking area of WS2/Bi2Se3 vertical heterojunctions were successfully modulated. High-quality WS2/Bi2Se3 vertical heterojunctions with various stacking areas were effectively grown from single and multiple nucleation sites. Moreover, the potential nucleation mechanism and efficient charge transfer of WS2/Bi2Se3 vertical heterojunctions were systematically studied by utilizing the density functional theory and photoluminescence spectra. This modified vapor deposition strategy and the proposed mechanism are helpful in controlling the nucleation density and stacking area of other heterojunctions, which plays a key role in the preparation of electronic and optoelectronic nanodevices.

Insight into the effect of particle size distribution differences on the antibacterial activity of carbon dots.

Carbon dots (CDs) have a profound effect on elimination of bacteria, fungi, and viruses, but the lack of an exact mechanism to interact with bacterial cells limits their development. Herein, we separated the CDs derived from chlorhexidine gluconate into three groups with uniformly small-scale, middle-scale, and large-scale particle sizes by using different molecular weight cut-off membranes. These positively charged particles exhibit significant antibacterial activity against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus; they can cause an increase in bacterial cell permeability, synergistic destabilization, and broken integrity of the plasma membrane. Impressively, we found that antibacterial activity increases as the size of the CDs decreases. This phenomenon may stem from the differences in cellular uptake and distribution of CDs in the plasma membrane or restriction between the polar functional group and DNA molecule. Our study of the size effect as a target may improve the understanding of killing microorganisms by antibacterial CD drugs.

Genipin cross-linked carbon dots for antimicrobial, bioimaging and bacterial discrimination.

Multifunctional carbon dots (CDs) present enormous potential in numerous applications and have attracted widespread attention for various applications in the biomedical field. Bacterial infection is a common health issue; the development of antibacterial materials with low toxicity and good biocompatibility is becoming more important. In this work, we synthesized a new type of nitrogen co-doped carbon dots-genipin covalent conjugate (N-CDs-GP) via hydrothermal methods. The microstructure and chemical composition of the N-CDs-GP were characterized. The biocompatibility, stability, antibacterial activity, and fluorescence performance of the N-CDs-GP were assessed. The results revealed that N-CDs-GP possessed high biocompatibility, high light stability, and broad antibacterial activity. Additionally, selective Gram-positive bacterial imaging by N-CDs-GP provided a more rapid method of bacterial detection. The N-CDs-GP have the potential to be applied as bioimaging and antibacterial agents and for bacterial discrimination.

Hollow Porous Carbon Coated FeS2-Based Nanocatalysts for Multimodal Imaging-Guided Photothermal, Starvation, and Triple-Enhanced Chemodynamic Therapy of Cancer.

Specific chemical reactions only happen in the tumor region and produce abundant special chemicals to in situ trigger a train of biological and pathological effects that may enable tumor-specific curative effects to treat cancer without causing serious side effects on normal cells or organs. Chemodynamic therapy (CDT) is a rising tactic for cancer therapy, which induces cancer cell death via a localized Fenton reaction. However, the tumor therapeutic effect is limited by the efficiency of the chemical reaction and relies heavily on the catalyst. Here, we constructed hollow porous carbon coated FeS2 (HPFeS2@C)-based nanocatalysts for triple-enhanced CDT. Tannic acid was encapsulated in HPFeS2@C for reducing Fe3+ to Fe2+, which had a better catalytic activity to accelerate the Fenton reaction. Afterward, glucose oxidase (GOx) in nanocatalysts could consume glucose in the tumor microenvironment and in situ synchronously produce H2O2, which could improve Fenton reaction efficiency. Meanwhile, the consumption of glucose could lead to the starvation effect for cancer starvation therapy. The photothermal effects of HPFeS2@C could generate heat, which further sped up the Fenton process and implemented synergetic photothermal therapy/starvation therapy/CDT. The biodistribution of nanoparticles was investigated by multimodal magnetic resonance, ultrasound, and photoacoustic imaging. These nanocatalysts could trigger the catalytic Fenton reaction at a high degree, which might provide a good paradigm for nanocatalytic tumor therapy.

Biomedical application of graphene: From drug delivery, tumor therapy, to theranostics.

The rise of graphene has driven great revolution in various fields, e. g. electronics, device, energy, etc., owing to the well-researched understanding of its physical and chemical properties. In the very recent decade, scientists have poured significant efforts to explore the biological functions of graphene and expand its biomedical applications, including drug delivery, tumor therapy, and theranostics. Encouraged by the inspiring research results and promising contributions of graphene to biomedicine field, herein, we systematically summarize the recent advance of graphene for biomedical application. In this review, we introduce the development of graphene in biomedicine, from drug delivery, tumor therapy, to theranostics. We also demonstrate the surface engineering and multifunctional modification of graphene, and further present the active role of rational decoration in drug delivery, therapy, and theranostic application. In detail, we summarize the surface engineering, active-targeting modification, stimuli-responsive decoration, and their application in anticancer drugs delivery, multiple therapeutic approach, dual-model imaging guided therapy. On the basis of the systematic summary, in the final, we further present the development tendency of graphene in biomedicine, aiming to provide some valuable guidelines for further research.

Quaternized Chitosan-Coated Montmorillonite Interior Antimicrobial Metal-Antibiotic in Situ Coordination Complexation for Mixed Infections of Wounds.

Conventional drug delivery systems for natural clay materials still face critical challenges in their practical application, including multiple bacterial infections, combined infection of bacteria and fungi, and low sterilization efficiency. In this work, we address these challenges using the multifunctional montmorillonite nanosheet-based (MMT-based) drug nanoplatform, which involves the antibiotic 5-fluorocytosine (5-FC), antibacterial metal copper ions, and quaternized chitosan (QCS). Composite material QCS/MMT/5-FCCu can can strongly inhibit Staphylococcus aureus (a typical Gram-positive bacterium), Escherichia coli (a typical Gram-negative bacterium), and Candida albicans (a fungus) because 5-FC coordinates with copper ions in situ and due to the deposition of QCS. The subsequent drug release behavior of 5-FCCu was studied, and the results show an initial high concentration kills microorganisms and long-acting sustained release inhibition. Moreover, in vivo wound experiments and toxicity experiments show the promotion of wound healing and excellent biocompatibility. As a demonstration of the utility of the latter, we have shown that the MMT-based smart platform can be used for the treatment of mixed infections of wounds.