Psoralen and Isopsoralen, Two Estrogen-Like Natural Products from Psoraleae Fructus, Induced Cholestasis via Activation of ERK1/2.

With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1b and the levels of E2 and VTG at 80 µM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1 and cyp8b1, BAs transport genes abcb11b and slc10a1, and BAs receptor genes nr1h4 and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.

ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.

Glioblastoma (GBM) is the most prevalent and fatal form of brain tumor, which is associated with a poor prognosis. ATP-binding cassette subfamily F member 1 (ABCF1) is an E2 ubiquitin-conjugating enzyme, which is implicated in regulating immune responses and tumorigenesis. Aberrant E3 ubiquitylation has been evidenced in GBM. However, the role of ABCF1 in GBM needs to be further explored. The expression of ABCF1, CXC chemokine ligand 12 (CXCL12), and CXC chemokine receptor 4 (CXCR4) in GBM tissues was examined by the GEPIA tool, real-time PCR and Western blotting. HMC3, U251MG, and LN-229 cells were cultured and transfected with shRNA targeting ABCF1 and ABCF1 plasmids. The proliferative, migrative, and invasive ability of cells was detected. Western blotting was used to detect the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (AKT). We observed that GBM tissues had higher ABCF1, CXCL12, and CXCR4 expression levels. The expression levels of CXCL12 and CXCR4 were enhanced by ABCF1 overexpression, which were significantly reversed by silence of ABCF1 in GBM cells. Silencing ABCF1 or CXCR4 inhibition weakened the capacity of GBM cell growth, migration, and invasion, while ectopic ABCF1 expression or CXCL12 treatment enhanced the cellular function of GBM cells. Furthermore, p-PI3K and p-AKT protein levels were downregulated by ABCF1 knockdown or CXCR4 blockade, which were prompted by ABCF1 overexpression or CXCL12 supplement. The ABCF1-CXCL12-CXCR4 axis was identified as a key player in GBM cell survival and metastasis by activating the PI3K/AKT signaling pathway in GBM cells.

Compound heterozygous missense mutations in a Chinese mucopolysaccharidosis type VI patient: a case report.

BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B (ARSB) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body. In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis. CASE PRESENTATION: A 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI. CONCLUSIONS: This paper reports a case of MPS VI confirmed by genetic diagnosis. MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

Isoliquiritin promote angiogenesis by recruiting macrophages to improve the healing of zebrafish wounds.

Licorice is a widely used herbal medicine for the treatment of various diseases in southern Europe and parts of Asia. It has been reported that the isoliquiritin (ISL) from Glycyrrhiza root has the activity of promoting angiogenesis. The purpose of this study was to investigate the effect of ISL on the wound healing activity of zebrafish and its mechanism. 6-month-old zebrafish were injured in the skin (2 mm in diameter) and then treated with ISL. By measuring wound size and by histological examination, we found that ISL improved wound healing. In addition, 4-day-old zebrafish embryos of double transgenic line [Tg(fli-1:EGFP)]/[Tg(mpeg:mCherry)] were suffered from tissue traumas and then treated with ISL. Through fluorescent microscopy, we found that ISL promoted macrophage recruitment and angiogenesis in the wound area. Through qPCR analysis, we found that ISL up-regulated the expression of genes related to inflammation and angiogenesis in zebrafish embryos. These results showed that ISL could promote inflammatory response and angiogenesis, which played key roles in promoting wound healing. Therefore, ISL can be used as a promising candidate to promote wound healing.

Ferrocene Functionalized Upconversion Nanoparticle Nanosystem with Efficient Near-Infrared-Light-Promoted Fenton-Like Reaction for Tumor Growth Suppression.

By taking advantage of the efficient Förster resonance energy transfer (FRET) between near-infrared (NIR)-responsive lanthanide-doped upconversion nanoparticles (UCNPs) and Fenton reagent ferrocenyl compounds (Fc), a series of Fc-UCNPs was designed by functionalizing NaYF4:Yb,Tm nanoparticles with Fc1-Fc5 via surface-coordination chemistry. Fc-UCNP-Lipo nanosystems were then constructed by encapsulating Fc-UCNP inside liposomes for efficient delivery. Fc-UCNP can effectively release ·OH via a NIR-promoted Fenton-like reaction. In vitro and in vivo studies of Fc1-UCNP-Lipo confirmed the preferential accumulation in a tumor site followed by an enhanced uptake of cancer cells. After cellular internalization, the released Fc1-UCNP can effectively promote ·OH generation for tumor growth suppression. Such a Fc1-UCNP-Lipo nanosystem exhibits advantages such as easy fabrication, low drug dosage, and no ferrous ion release.

Developmental toxicity of auranofin in zebrafish embryos.

Auranofin (AF) is used in clinic for the treatment of rheumatoid arthritis, repurposing of AF as an anticancer drug has just finished a phase I/II clinical trial, but the developmental toxicity of AF remains obscure. This study focused on its developmental toxicity by using zebrafish embryos. Zebrafish embryos were exposed to different concentrations (1, 2.5, 5, 10 µm) of AF from 2 h post-fertilization (hpf) to 72 hpf. At 72 hpf, two major developmental defects caused by AF were found, namely severe pericardial edema and hypopigmentation, when embryos were exposed to concentrations higher than 2.5 µm. Biochemical detection of oxidative stress enzyme combined with expressions of a series of genes related to oxidative stress, cardiac, metal stress and pigment formation were subsequently tested. The superoxide dismutase activity was decreased while malondialdehyde content was accumulated by AF treatment. The expression of oxidative stress-related genes (sod1, gpx1a, gst), pigment-related genes (mitfb, trp-1a) and one metal stress-related gene ctr1 were all decreased by AF exposure. The expressions of cardiac-related genes (amhc, vmhc) and one metal-related gene hsp70 were found to be significantly upregulated by AF exposure. These findings indicated the potential developmental toxicity of AF on zebrafish early development. Copyright © 2016 John Wiley & Sons, Ltd.

Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways.

OBJECTIVE: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3). METHODS: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish. RESULTS: Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01). CONCLUSIONS: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

Mycophenolic Acid-Induced Developmental Defects in Zebrafish Embryos.

With the increasing use of mycophenolic acid (MPA) in solid organ transplantation, some clinical studies indicate that it is also a human teratogen. However, it is unknown by which mechanism MPA acts as a teratogen. Mycophenolic acid was a selective blocker of de novo purine synthesis, and its immunosuppressive effect is mediated by the inhibition of inosine monophosphate dehydrogenase, which could be a target for MPA-induced toxicity as well. The aim of our study was to examine the direct influence of MPA exposure on zebrafish (Danio rerio) embryos. Morphological defects including tail curvature and severe pericardial edema in zebrafish embryos caused by MPA (3.7-11.1 µmol/L) were found in a dose-dependent manner. The teratogenic index (25% lethal concentration value (LC25)/no observed adverse effect level ratio) was 16, which indicated MPA as a teratogen. Quantitative polymerase chain reaction analysis revealed that the expression level of impdh1b and impdh2 was significantly reduced by MPA treatment at 8 µmol/L (equals to LC25 level). All the toxic effects could be partially reversed by the addition of 33.3 µmol/L guanosine. Our results indicated that MPA impairs the development of zebrafish embryos via inhibition of impdh activity, which subsequently caused a guanosine nucleotide depletion in vivo.

Twelve serum proteins progressively increase with disease stage in squamous cell cervical cancer patients.

OBJECTIVE: This study aimed to reliably identify serum protein profile alterations that may be useful for elucidation of the disease mechanism and/or finding new targets for treatment and intervention. MATERIALS AND METHODS: A total of 1057 women at 4 different squamous cell cervical cancer stages (noninvasive, invasive International Federation of Gynecology and Obstetrics stages I, II, and III) were included in this cross-sectional study. Forty-seven serum proteins were profiled using multiplex Luminex immunoassays. RESULTS: Serum concentration of serum amyloid A (SAA), C-reactive protein (CRP), soluble tumor necrosis factor receptor I and II (sTNFRI and sTNFRII), soluble interleukin 2 receptor α (sIL2Rα), CXCL1, CXCL9, hepatocyte growth factor, squamous cell carcinoma antigen (SCCA), insulin-like growth factor binding protein 2, CA125, and carcinoembryonic antigen (CEA) were elevated significantly as disease progressed in cervical cancer patients. Serum levels are significantly different at early stage (I) for SAA, CRP, sIL2Rα, sTNFRII, SCCA, and CEA (P values ranged from 0.02 for CEA to 0.0001 for CRP and SCCA) and at late stages (II and III) for all 12 proteins (P values ranged from 8.78E-5 for CA125 to 3.49E-47 for SAA), as compared to the noninvasive stage. The areas under the curves of these proteins for disease state separation also improved with the advancement of the disease. The correlations between serum concentrations of these proteins also show different patterns at different clinical stages. These proteins are involved in multiple mechanisms including inflammation and immunity, angiogenesis, growth promotion, and metastasis. CONCLUSIONS: A number of serum proteins are significantly different between patients at different stages of cervical cancer.

Toxicity assessment of 7 anticancer compounds in zebrafish.

Toxicity is one of the major reasons for failure in drug development. Zebrafish, as an ideal vertebrate model, could also be used to evaluate drug toxicity. In this study, we aimed to show the predictability and highlight novel findings of toxicity in zebrafish model. Seven anticancer compounds, including triptolide (TP), gambogic acid (GA), mycophenolic acid (MPA), curcumin, auranofin, thalidomide, and taxol, were assessed in zebrafish for their toxicity. Three compounds (GA, TP, and taxol) showed highest acute lethality, with 50% lethal concentration ≈ 1 µmol/L. Missing tails, severe pericardial edema, and enlarged yolk sacs were observed in MPA-treated embryos. The development of pectoral fins was severely disturbed in thalidomide-, GA-, and TP-treated embryos. Bradycardia was observed in MPA- and thalidomide-treated groups. Our findings suggested that the zebrafish are a good model for toxicity assessment of anticancer compounds.

A High-Precision Identification Method for Maize Leaf Diseases and Pests Based on LFMNet under Complex Backgrounds.

Maize, as one of the most important crops in the world, faces severe challenges from various diseases and pests. The timely and accurate identification of maize leaf diseases and pests is of great significance for ensuring agricultural production. Currently, the identification of maize leaf diseases and pests faces two key challenges: (1) In the actual process of identifying leaf diseases and pests, complex backgrounds can interfere with the identification effect. (2) The subtle features of diseases and pests are difficult to accurately extract. To address these challenges, this study proposes a maize leaf disease and pest identification model called LFMNet. Firstly, the localized multi-scale inverted residual convolutional block (LMSB) is proposed to perform preliminary down-sampling on the image, preserving important feature information for the subsequent extraction of fine disease and pest features in the model structure. Then, the feature localization bottleneck (FLB) is proposed to improve the model's ability to focus on and locate disease and pest characteristics and to reduce interference from complex backgrounds. Subsequently, the multi-hop local-feature fusion architecture (MLFFA) is proposed, which effectively addresses the problem of extracting subtle features by enhancing the extraction and fusion of global and local disease and pest features in images. After training and testing on a dataset containing 19,451 images of maize leaf diseases and pests, the LFMNet model demonstrated excellent performance, with an average identification accuracy of 95.68%, a precision of 95.91%, a recall of 95.78%, and an F1 score of 95.83%. Compared to existing models, it exhibits significant advantages, offering robust technical support for the precise identification of maize diseases and pests.

A Dynamics-Learning Multirate Estimation Approach for the Feeding Condition Perception of Complex Industry Processes.

In this study, we propose a dynamics-learning multirate estimation approach to perceive the quality-related indices (QRIs) of the feeding solution of a unit process. A quality-related index for estimation is an intermediate technical indicator between a unit process and a proceeding unit process; hence, the estimation problem is formulated as a two-stage estimation problem utilizing the production data of both unit processes. Dynamics-learning bidirectional long short-term memory (BiLSTM) with different inputs for the forward and backward layers is proposed to manage the input data from the different unit processes. In the dynamics-learning BiLSTM, a cycle control gate is added in the memory cell to learn the dynamics of the QRIs, thereby enabling a high-rate estimation under multirate conditions. A Bayesian estimation model is then combined with the dynamics-learning BiLSTM model to manage the process delay. Ablation and comparative experiments are conducted to evaluate the feasibility and effectiveness of the proposed estimation approach. The experimental results illustrate the performance and high-rate estimation ability of the proposed approach.

Identification of Pepper Leaf Diseases Based on TPSAO-AMWNet.

Pepper is a high-economic-value agricultural crop that faces diverse disease challenges such as blight and anthracnose. These diseases not only reduce the yield of pepper but, in severe cases, can also cause significant economic losses and threaten food security. The timely and accurate identification of pepper diseases is crucial. Image recognition technology plays a key role in this aspect by automating and efficiently identifying pepper diseases, helping agricultural workers to adopt and implement effective control strategies, alleviating the impact of diseases, and being of great importance for improving agricultural production efficiency and promoting sustainable agricultural development. In response to issues such as edge-blurring and the extraction of minute features in pepper disease image recognition, as well as the difficulty in determining the optimal learning rate during the training process of traditional pepper disease identification networks, a new pepper disease recognition model based on the TPSAO-AMWNet is proposed. First, an Adaptive Residual Pyramid Convolution (ARPC) structure combined with a Squeeze-and-Excitation (SE) module is proposed to solve the problem of edge-blurring by utilizing adaptivity and channel attention; secondly, to address the issue of micro-feature extraction, Minor Triplet Disease Focus Attention (MTDFA) is proposed to enhance the capture of local details of pepper leaf disease features while maintaining attention to global features, reducing interference from irrelevant regions; then, a mixed loss function combining Weighted Focal Loss and L2 regularization (WfrLoss) is introduced to refine the learning strategy during dataset processing, enhancing the model's performance and generalization capabilities while preventing overfitting. Subsequently, to tackle the challenge of determining the optimal learning rate, the tent particle snow ablation optimizer (TPSAO) is developed to accurately identify the most effective learning rate. The TPSAO-AMWNet model, trained on our custom datasets, is evaluated against other existing methods. The model attains an average accuracy of 93.52% and an F1 score of 93.15%, demonstrating robust effectiveness and practicality in classifying pepper diseases. These results also offer valuable insights for disease detection in various other crops.

CRLNet: A Multimodal Peach Detection Network Based on Cooperative Asymptotic Enhancement and the Fusion of Granularity Refinement.

Accurate peach detection is essential for automated agronomic management, such as mechanical peach harvesting. However, ubiquitous occlusion makes identifying peaches from complex backgrounds extremely challenging. In addition, it is difficult to capture fine-grained peach features from a single RGB image, which can suffer from light and noise in scenarios with dense small target clusters and extreme light. To solve these problems, this study proposes a multimodal detector, called CRLNet, based on RGB and depth images. First, YOLOv9 was extended to design a backbone network that can extract RGB and depth features in parallel from an image. Second, to address the problem of information fusion bias, the Rough-Fine Hybrid Attention Fusion Module (RFAM) was designed to combine the advantageous information of different modes while suppressing the hollow noise at the edge of the peach. Finally, a Transformer-based Local-Global Joint Enhancement Module (LGEM) was developed to jointly enhance the local and global features of peaches using information from different modalities in order to enhance the percentage of information about the target peaches and remove the interference of redundant background information. CRLNet was trained on the Peach dataset and evaluated against other state-of-the-art methods; the model achieved an mAP50 of 97.1%. In addition, CRLNet also achieved an mAP50 of 92.4% in generalized experiments, validating its strong generalization capability. These results provide valuable insights for peach and other outdoor fruit multimodal detection.

Benzorhodol derived far-red/near-infrared fluorescent probes for selective and sensitive detection of butyrylcholinesterase activity in living cells and the non-alcoholic fatty liver of zebrafish.

Liver diseases are a growing public health concern and the development of non-alcoholic fatty liver disease (NAFLD) has a significant impact on human metabolism. Butyrylcholinesterase (BChE) is a vital biomarker for NAFLD, making it crucial to monitor BChE activity with high sensitivity and selectivity. In this study, we designed and synthesized a range of benzorhodol-derived far-red/near-infrared fluorescent probes, FRBN-B, NF-SB, and NF-B, for the quantitative detection and imaging of BChE. These probes differed in the size of their conjugated systems and in the number of incorporated cyclopropanecarboxylates, acting as the recognition site for BChE. Comprehensive characterization showed that FRBN-B and NF-SB fluorescence was triggered by BChE-mediated hydrolysis, while an additional cyclopropanecarboxylate in NF-B impeded the fluorescence release. High selectivity towards BChE was observed for FRBN-B and NF-SB, with a detection limit of 7.2 × 10-3 U mL-1 for FRBN-B and 1.9 × 10-3 U mL-1 for NF-SB. The probes were further employed in the evaluation of BChE inhibitor efficacy and imaging of intracellular BChE activity. Additionally, FRBN-B was utilized for imaging the BChE activity level in liver tissues in zebrafish, demonstrating its potential as a diagnostic tool for NAFLD.

Efficacy and Mechanism Study of 6S-5-Methyltetrahydrofolate-Calcium Against Telencephalon Infarction Injury in Zebrafish Model of Ischemic Stroke.

Ischemic stroke is a heterogeneous brain injury with complex pathophysiology and it is also a time sensitive neurological injury disease. At present, the treatment options for ischemic stroke are still limited. 6S-5-methyltetrahydrofolate-calcium (MTHF-Ca) is the calcium salt of the predominant form of dietary folate in circulation. MTHF-Ca has potential neuroprotective effect on neurocytes, but whether it can be used for ischemic stroke treatment remains unknown. We established zebrafish ischemic stroke model through photothrombotic method to evaluate the protective effect of MTHF-Ca on the ischemic brain injury of zebrafish. We demonstrated that MTHF-Ca reduced the brain damage by reducing motor dysfunction and neurobehavioral defects of zebrafish with telencephalon infarction injury. MTHF-Ca counteracted oxidative damages after Tel injury by increasing the activities of GSH-Px and SOD and decreasing the content of MDA. RNA-seq and RT-qPCR results showed that MTHF-Ca played a neuroprotective role by alleviating neuroinflammation, inhibiting blood coagulation, and neuronal apoptosis processes. Overall, we have demonstrated that MTHF-Ca has neuroprotective effect in ischemic stroke and can be used as a potential treatment for ischemic stroke.

Angiotensin-converting enzyme inhibitors provide a protective effect on hypoxia-induced injury in human coronary artery endothelial cells via Nrf2 signaling and PLVAP.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) were reported to protect from hypoxia-induced oxidative stress in coronary endothelial cells (CECs) after acute myocardial infarction (AMI). Nrf2 shows a protective effect in hypoxia-induced CECs after AMI. Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in angiogenesis after AMI. AIM: To explore the protective effect of ACEIs and the involved mechanisms under hypoxia challenge. METHODS: Human coronary endothelial cells (HCAECs) were used to establish hypoxia-induced oxidative stress injury in vitro. Flow cytometry was used to evaluate the protective effect of ACEI on hypoxia conditions.ET-1, NO, ROS, and VEGF were detected by ELISA. HO-1, Nrf2, and Keap-1, the pivotal member in the Nrf2 signaling pathway, eNOS and PLVAP were detected in HEAECs treated with ACEI by immunofluorescence, qPCR, and western blotting. RESULTS: The hypoxia ACEI or Nrf2 agonist groups showed higher cell viability compared with the hypoxia control group at 24 (61.75±1.16 or 61.23±0.59 vs. 44.24±0.58, both P < 0.05) and 48 h (41.85±1.19 or 59.64±1.13 vs. 22.98±0.25, both P < 0.05). ACEI decreased the levels of ET-1 and ROS under hypoxia challenge at 24 and 48 h (all P < 0.05); ACEI increased the VEGF and NO levels (all P < 0.05). ACEI promoted the expression level of eNOS, HO-1, Nrf2 and PLVAP but inhibited Keap-1 expression at the mRNA and protein levels (all P < 0.05). Blockade of the Nrf2 signaling pathway significantly decreased the expression level of PLVAP. CONCLUSION: ACEI protects hypoxia-treated HEAECs by activating the Nrf2 signaling pathway and upregulating the expression of PLVAP.

A comprehensive exploration of hydrogel applications in multi-stage skin wound healing.

Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.

A Multi-Modal Open Object Detection Model for Tomato Leaf Diseases with Strong Generalization Performance Using PDC-VLD.

Precise disease detection is crucial in modern precision agriculture, especially in ensuring the health of tomato crops and enhancing agricultural productivity and product quality. Although most existing disease detection methods have helped growers identify tomato leaf diseases to some extent, these methods typically target fixed categories. When faced with new diseases, extensive and costly manual annotation is required to retrain the dataset. To overcome these limitations, this study proposes a multimodal model PDC-VLD based on the open-vocabulary object detection (OVD) technology within the VLDet framework, which can accurately identify new tomato leaf diseases without manual annotation by using only image-text pairs. First, we developed a progressive visual transformer-convolutional pyramid module (PVT-C) that effectively extracts tomato leaf disease features and optimizes anchor box positioning using the self-supervised learning algorithm DINO, suppressing interference from irrelevant backgrounds. Then, a context feature guided module (CFG) was adopted to address the low adaptability and recognition accuracy of the model in data-scarce environments. To validate the model's effectiveness, we constructed a tomato leaf disease image dataset containing 4 base classes and 2 new categories. Experimental results show that the PDC-VLD model achieved 61.2% on the main evaluation metric mAP novel 50 , and 56.4% on mAP novel 75 , 87.7% on mAP base 50 , 81.0% on mAP all 50 , and 45.5% on average recall, outperforming existing OVD models. Our research provides an innovative solution for efficiently and accurately detecting new diseases, substantially reducing the need for manual annotation, and offering critical technical support and practical reference for agricultural workers.

Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS2-dithiothreitol nanozyme for treatment of infected wounds.

Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.