Recent design strategies for boosting chemodynamic therapy of bacterial infections.

The emergence of drug-resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into •OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.

Pillarurilarenes: Glycoluril-Expanded Pillararenes.

Glycoluril-expanded pillararenes composed of glycoluril and dialkoxybenzene units, namely, pillarurilarenes (PURA), were synthesized through a fragment coupling macrocyclization strategy. Partial replacement of dialkoxybenzene with glycoluril endows PURA with polarized equatorial methine protons for derivatization or CH-anion binding. Crystal structures of pillar[2]uril[4]arene and pillar[1]uril[4]arene containing two glycoluril units and one glycoluril unit, respectively, indicated the inward orientation of the glycoluril unit, as also suggested by 1H nuclear magnetic resonance and density functional theory calculation. This work lays a good foundation for expanding pillararenes using non-aromatic rings.

Layer-by-layer assembled decomposable nanocapsules for light-responsive release of pesticide imidacloprid on Aphis craccivora Koch.

BACKGROUND: Conventional pesticide formulations are often inefficient because of low biological uptake after spraying. Controlled release nanopesticides can release pesticides precisely in response to specific stimuli, thereby killing pests and pathogens using the least effective concentration. This study aims to develop nanocapsule-based photo-decomposable nanopesticides for efficient pesticide control. RESULTS: The target nanopesticides were successfully fabricated using layer-by-layer assembly of the negative azobenzene-grafted hyaluronic acid (azo-HA) and positive polydimethyldiallylammonium chloride (polyDADMAC), confirmed by UV-visible, dynamic light scattering, Zeta potential and transmission electron microscopy measurements. The particle size and Zeta potential of the fabricated nanocapsules were 220 nm and +46.1 mV, respectively, and the nanocapsules were found to remain stable for up to 30 days. The optimized drug loading and encapsulation ratio of imidacloprid (IMI) in IMI/azo-HA@polyDADMAC were 21.5% and 91.3%, respectively. Cumulative release of IMI from the nanopesticides increased from ~50% to ~95% upon UV light irradiation (365 nm). The half lethal concentration (LC50) value of the nanopesticides toward Aphis craccivora Koch decreased from 2.22 to 0.55 mg L-1 upon UV light irradiation. CONCLUSION: The trans to cis transformation of the azo group in HA decomposed IMI/azo-HA@polyDADMAC nanopesticides upon UV irradiation, thus facilitating the release of IMI, resulting in a decrease in the concentration of pesticides required for efficient pesticide control. Our work demonstrated the great potential of light-responsive nanocapsules as a controlled release nanocarrier for efficient and eco-friendly pesticide control in sustainable agriculture. © 2024 Society of Chemical Industry.

Fusion Surgery for Lumbar Spondylolisthesis: A Systematic Review with Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to systematically evaluate the optimal surgical fusion approach for lumbar spondylolisthesis, to provide the latest and most reliable evidence for future clinical practice. METHODS: A comprehensive search of the PubMed, Ovid-Embase, Web of Science, Cochrane, and Scopus databases was conducted from inception to September 1, 2023, to identify relevant records. Two independent reviewers performed the literature screening, data extraction, and assessment of study quality. RESULTS: Fifteen randomized controlled trials involving 892 patients met the inclusion criteria. The network evidence plot showed that posterolateral fusion and posterior lumbar interbody fusion (PLIF) were the most used fusion techniques. The network meta-analysis results revealed that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) had a significantly greater improvement in the Oswestry Disability Index (ODI) compared to endoscopic-TLIF, while PLIF had a significantly better fusion effect than posterolateral fusion. Furthermore, no statistically significant differences were observed between other fusion surgeries in terms of improving ODI, fusion rate, complications, or the improvement of visual analog scale-low back pain. The surface under the cumulative ranking curve results indicated that MIS-TLIF had the greatest potential for improving ODI, visual analog scale-low back pain, and complications, while PLIF had the greatest potential for increasing fusion rates. However, the existing selection bias, measurement bias, reporting bias, and publication bias may have reduced the reliability of the meta-analysis results. CONCLUSIONS: Among the various fusion surgeries for lumbar spondylolisthesis, MIS-TLIF appears to provide the greatest benefit to patients. However, more high-quality, large-scale studies are needed to further investigate the treatment efficacy of different fusion surgeries for lumbar spondylolisthesis.

CAENet: Contrast adaptively enhanced network for medical image segmentation based on a differentiable pooling function.

Pixel differences between classes with low contrast in medical image semantic segmentation tasks often lead to confusion in category classification, posing a typical challenge for recognition of small targets. To address this challenge, we propose a Contrastive Adaptive Augmented Semantic Segmentation Network with a differentiable pooling function. Firstly, an Adaptive Contrast Augmentation module is constructed to automatically extract local high-frequency information, thereby enhancing image details and accentuating the differences between classes. Subsequently, the Frequency-Efficient Channel Attention mechanism is designed to select useful features in the encoding phase, where multifrequency information is employed to extract channel features. One-dimensional convolutional cross-channel interactions are adopted to reduce model complexity. Finally, a differentiable approximation of max pooling is introduced in order to replace standard max pooling, strengthening the connectivity between neurons and reducing information loss caused by downsampling. We evaluated the effectiveness of our proposed method through several ablation experiments and comparison experiments under homogeneous conditions. The experimental results demonstrate that our method competes favorably with other state-of-the-art networks on five medical image datasets, including four public medical image datasets and one clinical image dataset. It can be effectively applied to medical image segmentation.

Supramolecularly Engineered Conjugate of Bacteria and Cell Membrane-Coated Magnetic Nanoparticles for Enhanced Ferroptosis and Immunotherapy of Tumors.

Although various ferroptosis inducers including magnetic nanoparticles (Fe3 O4 ) and iron-organic frameworks have been applied in cancer treatment, the mild immunogenicity, low targeting efficiency to the tumor, and poor tissue penetration have limited the therapeutic efficacy. Herein, a supramolecularly engineered conjugate between living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) and cancer cell membranes-coated Fe3 O4 nanoparticles is developed for improving targeted delivery of Fe3 O4 nanoparticles into the tumor tissue and for synergistic ferroptosis and immunotherapy of tumor. The enhanced ferroptosis induced by both Fe3 O4 nanoparticles and the loaded ferroptosis inducing agent (sulfasalazine (SAS)) effectively inhibits tumor growth and generates immune response via immunogenic cell death (ICD). The colonization of VNP in tumors also induces adaptive immune responses and further promotes ferroptosis. Fundamentally, the supramolecular conjugate of VNP and cell membranes-coated Fe3 O4 can potentiate the therapeutic capability of each other through mutually magnifying the ferroptosis and immunotherapy, resulting in significantly enhanced antitumor effects.

Development and Characterization of Near-Isogenic Lines Derived from Synthetic Wheat Revealing the 2 kb Insertion in the PPD-D1 Gene Responsible for Heading Delay and Grain Number Improvement.

Spikelet number and grain number per spike are two crucial and correlated traits for grain yield in wheat. Photoperiod-1 (Ppd-1) is a key regulator of inflorescence architecture and spikelet formation in wheat. In this study, near-isogenic lines derived from the cross of a synthetic hexaploid wheat and commercial cultivars generated by double top-cross and two-phase selection were evaluated for the number of days to heading and other agronomic traits. The results showed that heading time segregation was conferred by a single incomplete dominant gene PPD-D1, and the 2 kb insertion in the promoter region was responsible for the delay in heading. Meanwhile, slightly delayed heading plants and later heading plants obviously have advantages in grain number and spikelet number of the main spike compared with early heading plants. Utilization of PPD-D1 photoperiod sensitivity phenotype as a potential means to increase wheat yield potential.

Recent progress in nanozymes for the treatment of diabetic wounds.

The slow healing of diabetic wounds has seriously affected human health. Meanwhile, the open wounds are susceptible to bacterial infection. Clinical therapeutic methods such as antibiotic therapy, insulin treatment, and surgical debridement have made great achievements in the treatment of diabetic wounds. However, drug-resistant bacteria will develop after long-term use of antibiotics, resulting in decreased efficacy. To improve the therapeutic effect, increasing drug concentration is a common strategy in clinical practice, but it also brings serious side effects. In addition, hyperglycemia control or surgical debridement can easily bring negative effects to patients, such as hypoglycemia or damage of normal tissue. Therefore, it is essential to develop novel therapeutic strategies to effectively promote diabetic wound healing. In recent years, nanozyme-based diabetic wound therapeutic systems have received extensive attention because they possess the advantages of nanomaterials and natural enzymes. For example, nanozymes have the advantages of a small size and a high surface area to volume ratio, which can enhance the tissue penetration of nanozymes and increase the reactive active sites. Moreover, compared with natural enzymes, nanozymes have more stable catalytic activity, lower production cost, and stronger operability. In this review, we first reviewed the basic characteristics of diabetic wounds and then elaborated on the catalytic mechanism and action principle of different types of nanozymes in diabetic wounds from three aspects: controlling bacterial infection, controlling hyperglycemia, and relieving inflammation. Finally, the challenges, prospects and future implementation of nanozymes for diabetic wound healing are outlined.

Environment-Responsive Therapeutic Platforms for the Treatment of Implant Infection.

The application of medical implants has greatly improved the survival rate and life quality of patients. Nevertheless, in recent years, there are increasing cases of implant dysfunction or failure because of bacterial infections. Despite significant improvements in biomedicine, there are still serious challenges in the treatment of implant-related infections. With the formation of bacterial biofilms and the development of bacterial resistance, these limitations lead to a low efficacy of conventional antibiotics. To address these challenges, it is urgent to exploit innovative treatment strategies for implant-related infections. Based on these ideas, environment-responsive therapeutic platforms with high selectivity, low drug resistance, and minor dose-limiting toxicity have attracted widespread attention. By using exogenous/endogenous stimuli, the antibacterial activity of therapeutics can be activated on demand and exhibit remarkable therapeutic effects. Exogenous stimuli include photo, magnetism, microwave, and ultrasound. Endogenous stimuli mainly include the pathological characteristics of bacterial infections such as acidic pH, anomalous temperature, and abnormal enzymatic activities. In this review, the recent progress of environment-responsive therapeutic platforms with spatiotemporally controlled drug release/activation is systematically summarized. Afterward, the limitations and opportunities of these emerging platforms are highlighted. Finally, it is hoped that this review will offer novel ideas and techniques to combat implant-related infections.

Nanomaterials for photothermal cancer therapy.

Cancer has emerged as a pressing global public health issue, and improving the effectiveness of cancer treatment remains one of the foremost challenges of modern medicine. The primary clinical methods of treating cancer, including surgery, chemotherapy and radiotherapy, inevitably result in some adverse effects on the body. However, the advent of photothermal therapy offers an alternative route for cancer treatment. Photothermal therapy relies on photothermal agents with photothermal conversion capability to eliminate tumors at high temperatures, which offers advantages of high precision and low toxicity. As nanomaterials increasingly play a pivotal role in tumor prevention and treatment, nanomaterial-based photothermal therapy has gained significant attention owing to its superior photothermal properties and tumor-killing abilities. In this review, we briefly summarize and introduce the applications of common organic photothermal conversion materials (e.g., cyanine-based nanomaterials, porphyrin-based nanomaterials, polymer-based nanomaterials, etc.) and inorganic photothermal conversion materials (e.g., noble metal nanomaterials, carbon-based nanomaterials, etc.) in tumor photothermal therapy in recent years. Finally, the problems of photothermal nanomaterials in antitumour therapy applications are discussed. It is believed that nanomaterial-based photothermal therapy will have good application prospects in tumor treatment in the future.

Recent advances in Prussian blue-based photothermal therapy in cancer treatment.

Malignant tumours are a serious threat to human health. Traditional chemotherapy has achieved breakthrough improvements but also has significant detrimental effects, such as the development of drug resistance, immunosuppression, and even systemic toxicity. Photothermal therapy (PTT) is an emerging cancer therapy. Under light irradiation, the phototherapeutic agent converts optical energy into thermal energy and induces the hyperthermic death of target cells. To date, numerous photothermal agents have been developed. Prussian blue (PB) nanoparticles are among the most promising photothermal agents due to their excellent physicochemical properties, including photoacoustic and magnetic resonance imaging properties, photothermal conversion performance, and enzyme-like activity. By the construction of suitably designed PB-based nanotherapeutics, enhanced photothermal performance, targeting ability, multimodal therapy, and imaging-guided cancer therapy can be effectively and feasibly achieved. In this review, the recent advances in PB-based photothermal combinatorial therapy and imaging-guided cancer therapy are comprehensively summarized. Finally, the potential obstacles of future research and clinical translation are discussed.

Hyaluronic acid-based supramolecular nanomedicine with optimized ratio of oxaliplatin/chlorin e6 for combined chemotherapy and O2-economized photodynamic therapy.

Dual- or multi-modality combination therapy has become one of the most effective strategies to overcome drug resistance in cancer therapy, and the optimized ratio of the therapeutic agents working on the tumor greatly affects the therapeutic outcomes. However, the absence of a facile method to optimize the ratio of therapeutic agents in nanomedicine has, at least in part, impaired the clinical potential of combination therapy. Herein, a new cucurbit[7]uril (CB[7])-conjugated hyaluronic acid (HA) based nanomedicine was developed, in which both chlorin e6 (Ce6) and oxaliplatin (OX) were co-loaded non-covalently at an optimized ratio via facile host-guest complexation, for optimal, combined photodynamic therapy (PDT)/chemotherapy. To maximize the therapeutic efficacy, a mitochondrial respiration inhibitor, atovaquone (Ato), was also loaded into the nanomedicine to limit consumption of oxygen by the solid tumor, sparing oxygen for more efficient PDT. Additionally, HA on the surface of nanomedicine allowed targeted delivery to cancer cells with over-expressed CD44 receptors (such as CT26 cell lines). Thus, this supramolecular nanomedicine platform with an optimal ratio of photosensitizer and chemotherapeutic agent not only provides an important new tool for enhanced PDT/chemotherapy of solid tumors, but also offers a CB[7]-based host-guest complexation strategy to facilely optimize the ratio of therapeutic agents for multi-modality nanomedicine. STATEMENT OF SIGNIFICANCE: Chemotherapy remains the most common modality for cancer treatment in clinical practice. Combination therapy by co-delivery of two or more therapeutic agents has been recognized as one of the most effective strategies to improve therapeutic outcome of cancer treatment. However, the ratio of loaded drugs could not be facilely optimized, which may greatly affect the combination efficiency and overall therapeutic outcome. Herein, we developed a hyaluronic acid based supramolecular nanomedicine with facile method to optimize the ratio of two therapeutic agents for improved therapeutic outcome. This supramolecular nanomedicine not only provides an important new tool for enhanced photodynamic therapy/chemotherapy of solid tumors, but also offers insights in using macrocyclic molecule-based host-guest complexation to facilely optimize the ratio of therapeutic agents in multi-modality nanomedicine.

Variation in the tonoplast cadmium transporter heavy metal ATPase 3 (HMA3) homolog gene in Aegilops tauschii.

The functionality of HMA3 is a key determinant controlling Cd accumulation in the shoots and grains of plants. Wild relatives of modern crop plants can serve as sources of valuable genetic variation for various traits. Here, resequencing of HMA3 homoeologous genes from Aegilops tauschii (the donor of the wheat D genome) was carried out to identify natural variation at both the nucleotide and polypeptide levels. HMA3 homoeologs are highly conserved, and 10 haplotypes were revealed based on 19 single nucleotide polymorphisms (eight induced single amino acid residue substitutions, including 2 altered amino acids in transmembrane domains) in 80 widely distributed Ae. tauschii accessions. The results provide genetic resources for low/no Cd concentration wheat improvement.

Non-Covalent Dimer as Donor Chromophore for Constructing Artificial Light-Harvesting System in Water.

Dynamic emissive materials in aqueous media have received much attention owing to their ease of preparation, tunable luminescence and environmental friendliness. However, hydrophobic fluorophores usually suffer from aggregation-caused quenching in water. In this work, we constructed an artificial light-harvesting system by using a non-covalent aggregation-induced emission dimer as antenna and energy donor. The dimer is quadruple hydrogen bonded from a ureidopyrimidinone derivative (M) containing a tetraphenylethylene group. The dispersed nano-assemblies based on the dimer in aqueous media were fabricated with the help of surfactant. By loading a hydrophobic acceptor molecule DBT into the nano-assemblies, man-made light-harvesting nanoparticles were fabricated, showing considerable energy transfer efficiency and a relatively high antenna effect. Additionally, the fluorescence color of the system can be gradually tuned by varying the content of the acceptors. This study provides a general way for the construction of an aqueous light-harvesting system based on a supramolecular dimer, which is important for potential application in luminescent materials.

Imidacloprid-loaded mesoporous silica nanoparticles simultaneously coated with myristyl alcohol and polydopamine for NIR-triggered delivery on Aphis craccivora Koch.

The stimuli-responsive degradation of coating layer on pesticide-loaded mesoporous silica nanoparticles (MSNs) can realize on-demand release of pesticides. Herein, we report the simultaneously coating of imidacloprid (IMI)-loaded MSNs with phase change materials (PCMs) and polydopamine (PDA) to realize NIR-triggered release of IMI. To balance good thermal stability and sensitive thermal responsiveness, myristyl alcohol (MA) was selected as optimal PCM for IMI@MSNs@MA-PDA nanocomposites. The successful preparation of IMI@MSNs@MA-PDA nanocomposites was confirmed by FT-IR, small angle XRD, SEM, TEM, TGA and BET. MSNs@MA-PDA nanocomposites exhibited concentration and irradiation power dependent stable photothermal conversion ability, with the maximum temperature increase of 23.3 â„ƒ (808 nm, 2 W/cm2, 300 µg/mL). The drug loading and encapsulation efficiency of IMI were 30.1% and 43.0%, respectively. The cumulative release of IMI from IMI@MSNs@MA-PDA was increased by ∼30% when the temperature was increased from 25 â„ƒ to 38 â„ƒ. Meanwhile, initial burst release of IMI from MSNs was inhibited. Finally, in vivo insecticidal activity of IMI@MSNs@MA-PDA was evaluated on Aphis craccivora Koch. The LC50 value was decreased from 5.01 mg/L to 3.73 mg/L, resulted from photothermal-boosted release of IMI. Our facile and effective method to prepare MSNs-based photothermal-responsive pesticide delivery system can be generalized to prepare other nanomaterials-based delivery systems for efficient and eco-friendly pesticide-control in agriculture.

A self-healing, magnetic and injectable biopolymer hydrogel generated by dual cross-linking for drug delivery and bone repair.

Injectable hydrogels based on various functional biocompatible materials have made rapid progress in the field of bone repair. In this study, a self-healing and injectable polysaccharide-based hydrogel was prepared for bone tissue engineering. The hydrogel was made of carboxymethyl chitosan (CMCS) and calcium pre-cross-linked oxidized gellan gum (OGG) cross-linked by the Schiff-base reaction. Meanwhile, magnetic hydroxyapatite/gelatin microspheres (MHGMs) were prepared by the emulsion cross-linking method. The antibacterial drugs, tetracycline hydrochloride (TH) and silver sulfadiazine (AgSD), were embedded into the MHGMs. To improve the mechanical and biological properties of the hydrogels, composite hydrogels were prepared by compounding hydroxyapatite (HAp) and drug-embedded MHGMs. The physical, chemical, mechanical and rheological properties of the composite hydrogels were characterized, as well as in vitro antibacterial tests and biocompatibility assays, respectively. Our results showed that the composite hydrogel with 6% (w/v) HAp and 10 mg/mL MHGMs exhibited good magnetic responsiveness, self-healing and injectability. Compared with the pure hydrogel, the composite hydrogel showed a 38.8% reduction in gelation time (196 to 120 s), a 65.6% decrease in swelling rate (39.4 to 13.6), a 51.9% increase in mass residual after degradation (79.5 to 120.8%), and a 143.7% increase in maximum compressive stress (53.6 to 130.6 KPa). In addition, this composite hydrogel showed good drug retardation properties and antibacterial effects against both S. aureus and E. coli. CCK-8 assay showed that composite hydrogel maintained high cell viability (> 87%) and rapid cell proliferation after 3 days, indicating that this smart hydrogel is expected to be an alternative scaffold for drug delivery and bone regeneration. STATEMENT OF SIGNIFICANCE: Biopolymer hydrogels have been considered as the promising materials for the treatment of tissue engineering and drug delivery. Injectable hydrogels with and self-healing properties and responsiveness to external stimuli have been extensively investigated as cell scaffolds and bone defects, due to their diversity and prolonged lifetime. Magnetism has also been involved in biomedical applications and played significant roles in targeted drug delivery and anti-cancer therapy. We speculate that development of dual cross-linked hydrogels basing biopolymers with multi-functionalities, such as injectable, self-healing, magnetic and anti-bacterial properties, would greatly broaden the application for bone tissue regeneration and drug delivery.

Stimuli-responsive therapeutic systems for the treatment of diabetic infected wounds.

Diabetic wound infection is a common disease that has significantly reduced people's quality of life. Although tremendous achievements have been made in clinical treatment, the crucial challenge in diabetic infected wound management stems from the detrimental diabetic wound environment and the emergence of bacterial resistance after long-term medication, which result in a reduced efficacy, an increased dosage of medication, and severe side effects. To tackle these issues, it is of great significance to develop an innovative treatment strategy for diabetic wound infection therapy. Currently, the exploitation of nanobiomaterial-based therapeutic systems for diabetic infected wounds is booming, and therapeutic systems with a stimuli-responsive performance have received extensive attention. These therapeutic systems are able to accelerate diabetic infected wound healing due to the on-demand release of therapeutic agents in diabetic infected wounds in response to stimulating factors. Based on the characteristics of diabetic infected wounds, many endogenous stimuli-responsive (e.g., glucose, enzyme, hypoxia, and acidity) therapeutic systems have been employed for the targeted treatment of infected wounds in diabetic patients. Additionally, exogenous stimulants, including light, magnetism, and temperature, are also capable of achieving on-demand drug release and activation. In this review, the characteristics of diabetic infected wounds are presented, and then exogenous/endogenous stimuli therapeutic systems for the treatment of diabetic infected wounds are summarized. Finally, the current challenges and future outlook of stimuli-responsive therapeutic systems are also discussed.

Hyaluronic acid-based supramolecular medicine with polyamines sequestration capability for cooperative anti-psoriasis.

Psoriasis seriously harms physical and mental health of patients. Hyaluronic acid (HA)-based topical formulation can increase drug concentration in psoriatic skin via CD44-assisted targeting. Herein, we developed a supramolecular medicine composed of curcumin-loaded HA-cucurbit[7]uril (HA-CB[7]@Cur), which could efficiently sequester polyamines (PAs) via host-guest interactions of CB[7] and PAs to suppress RNA-PAs immunocomplex formation. Meanwhile, anti-psoriasis drug Cur could be released from HA-CB[7]@Cur by PAs. With phenotypical disease evaluation, psoriasis area measurements and severity index scoring, and histological characterizations, we demonstrate topical administration of Carbopol gel formulation of HA-CB[7]@Cur on psoriasis-like skin in mice exhibited an enhanced anti-psoriasis activity, in comparison with gel of free Cur or HA-CB[7]. Cytokine expression analysis in psoriatic skin also supported the observed therapeutic outcomes. We provide a novel and effective supramolecular strategy to realize cooperative anti-psoriasis via controlled release of curcumin and PAs sequestration, which can be potentially expanded to treat other PA-involved skin inflammatory diseases.

Supramolecularly functionalized platelets for rapid control of hemorrhage.

Excessive bleeding has always been of great medical challenge, particularly in trauma and surgery. Due to the fast clearance of medicine and complex hemodynamics during hemorrhage, it is often difficult to achieve rapid and effective hemostasis on irregularly shaped, noncompressible visceral bleeding wounds. Herein, we report a hemostatic derived from supramolecularly functionalized platelets (SPLTs), showing rapid hemorrhage controlling effects via efficiently targeting injured vessels and in-situ aggregation. Von Willebrand factor-binding peptide (VBP) modified hyaluronic acid (HA-VBP) decorated platelets (PLTs) were fabricated via supramolecular host-guest interactions between cucurbit[7]uril (CB[7], a host molecule) modified on HA-VBP (HA-CB[7]-VBP) and adamantane (ADA, a guest molecule) anchored on the surface of PLTs (ADA-PLTs). The SPLTs demonstrated approximately 10-fold improvements than the native PLTs in the targeting efficiency into the injured vessels in mice upon intravenous injection. More significantly, the total bleeding time and bleeding volume were dramatically reduced down to less than 1/4 and 1/10 of the control group, respectively, in both external and internal major bleeding mice models. This SPLTs provide a facile yet effective approach for rapid control of major hemorrhage and offers important new insights to the design and development PLTs-based hemostatics. STATEMENT OF SIGNIFICANCE: Hemorrhage is one of the greatest threats to humans in trauma and surgery. To reduce bleeding volume and time, transfusion of hematological products such as platelets (PLTs)-rich plasma is one of the most commonly used therapeutics, but with low targeting and hemostatic efficiency. Thus, engineered PLTs with expanded structural repertoire and functionalities are in urgent clinical needs. Herein, we developed supramolecularly functionalized PLTs (SPLTs), prepared with a mild and facile approach, for rapid control of hemorrhage with significantly enhanced targeting efficiency. The SPLTs not only provide a facile approach for rapid control of major hemorrhage, but also offer important new insights into the development PLTs-based hemostatics.

MEA-Net: multilayer edge attention network for medical image segmentation.

Medical image segmentation is a fundamental step in medical analysis and diagnosis. In recent years, deep learning networks have been used for precise segmentation. Numerous improved encoder-decoder structures have been proposed for various segmentation tasks. However, high-level features have gained more research attention than the abundant low-level features in the early stages of segmentation. Consequently, the learning of edge feature maps has been limited, which can lead to ambiguous boundaries of the predicted results. Inspired by the encoder-decoder network and attention mechanism, this study investigates a novel multilayer edge attention network (MEA-Net) to fully utilize the edge information in the encoding stages. MEA-Net comprises three major components: a feature encoder module, a feature decoder module, and an edge module. An edge feature extraction module in the edge module is designed to produce edge feature maps by a sequence of convolution operations so as to integrate the inconsistent edge information from different encoding stages. A multilayer attention guidance module is designed to use each attention feature map to filter edge information and select important and useful features. Through experiments, MEA-Net is evaluated on four medical image datasets, including tongue images, retinal vessel images, lung images, and clinical images. The evaluation values of the Accuracy of four medical image datasets are 0.9957, 0.9736, 0.9942, and 0.9993, respectively. The values of the Dice coefficient are 0.9902, 0.8377, 0.9885, and 0.9704, respectively. Experimental results demonstrate that the network being studied outperforms current state-of-the-art methods in terms of the five commonly used evaluation metrics. The proposed MEA-Net can be used for the early diagnosis of relevant diseases. In addition, clinicians can obtain more accurate clinical information from segmented medical images.