Research progress on the environmental risk assessment and remediation technologies of heavy metal pollution in agricultural soil.

Controlling heavy metal pollution in agricultural soil has been a significant challenge. These heavy metals seriously threaten the surrounding ecological environment and human health. The effective assessment and remediation of heavy metals in agricultural soils are crucial. These two aspects support each other, forming a close and complete decision-making chain. Therefore, this review systematically summarizes the distribution characteristics of soil heavy metal pollution, the correlation between soil and crop heavy metal contents, the presence pattern and migration and transformation mode of heavy metals in the soil-crop system. The advantages and disadvantages of the risk evaluation tools and models of heavy metal pollution in farmland are further outlined, which provides important guidance for an in-depth understanding of the characteristics of heavy metal pollution in farmland soils and the assessment of the environmental risk. Soil remediation strategies involve multiple physical, chemical, biological and even combined technologies, and this paper compares the potential and effect of the above current remediation technologies in heavy metal polluted farmland soils. Finally, the main problems and possible research directions of future heavy metal risk assessment and remediation technologies in agricultural soils are prospected. This review provides new ideas for effective assessment and selection of remediation technologies based on the characterization of soil heavy metals.

A novel 3D multimodal fusion imaging surgical guidance in microvascular decompression for primary trigeminal neuralgia and hemifacial spasm.

BACKGROUND: Neurovascular compression (NVC) is a primary etiology of trigeminal neuralgia (TN) and hemifacial spasm (HFS). Despite Magnetic Resonance Tomographic Angiography (MRTA) being a useful tool for 3D multimodal fusion imaging (MFI) in microvascular decompression (MVD) surgery planning, it may not visualize smaller arterial vessels and veins effectively. We validate a novel computed tomography angiography and venography (CTA/V) - diffusion tensor tractography (DTT) -3D-MFI to enhance the MVD surgical guidance. METHODS: In this prospective study, 80 patients with unilateral primary TN or HFS who underwent MVD surgery were included. Imaging was conducted using CTA/V-DTT-3D-MFI compared with CT-MRTA-3D-MFI in predicting the responsible vessel and assessing the severity of NVC. Surgical outcomes were subsequently analyzed. Neurosurgery residents were provided with questionnaires to evaluate and compare the two approaches. RESULTS: CTA/V-DTT-3D-MFI significantly improved accuracy in identifying the responsible vessel (kappa = 0.954) and NVC (kappa = 0.969) compared to CT-MRTA-3D-MFI, aligning well with surgical findings. CTA/V-DTT-3D-MFI also exhibited higher sensitivity in identifying responsible vessels (98.0%) and NVC (98.7%) than CT-MRTA-3D-MFI. Additionally, CTA/V-DTT-3D-MFI showed fewer complications, shorter operation times, and lower recurrence after one year (all p < 0.05). Resident neurosurgeons emphasized that CTA/V-DTT-3D-MFI greatly assisted in formulating precise surgical strategies for more accurate identification and protection of responsible vessels and nerves (all p < 0.001). CONCLUSION: CTA/V-DTT-3D-MFI enhances MVD surgery guidance, improving accuracy in identifying responsible vessels and NVC for better outcomes. This advanced imaging plays a crucial role in safer and more effective MVD surgery, as well as in training neurosurgeons.

Biodiversity-safeguarding threshold for urea-fertilizer application on paddy fields: Protozoa-based toxicity tests.

Urea is a widely applied fertilizer to enhance crop yields. Ecological risks associated with the excessive application of urea fertilizer threaten the paddy fields' sustainable agriculture and biodiversity preservation. There are no practical thresholds based on proven data on microbial communities. Protozoa are nitrogen-sensitive organisms. For the first time, this study conducted acute and chronic urea toxicity tests on eight species of organisms. The results indicate that Blepharisma sp. is the most sensitive species to urea exposure and is a suitable indicator for determining the safe threshold of urea. This study estimated the predicted no-effect concentration using species sensitivity distribution curves. Subsequently, it established the threshold for urea application in rice fields based on the fields' area and the surface water's height. The short-term safety threshold for urea in the studied paddy field with black soil is 87.7 mg/L, equivalent to 43.85 kg of urea per hectare for a single nitrogen fertilizer application. The long-term safety threshold is 5.02 mg/L, representing the concentration for re-applicating urea. The biodiversity-safeguarding application threshold provides the basis for developing a urea fertilizer reduction protocol to safeguard the paddy fields' biodiversity.

Comparative transcriptome analysis and identification of candidate bZIP transcription factors involved in anthraquinone biosynthesis in Rheum officinale Baill.

Rhubarb is a traditional medicinal plant in China, whose pharmacological effects derive mainly from its anthraquinones. However, the regulatory mechanism affecting anthraquinone biosynthesis in R. officinale remains poorly understood. We assembled a high-quality, full-length transcriptome using single-molecule real-time (SMRT) sequencing. 274 unigenes potentially involved in the biosynthesis of anthraquinones, including those in the shikimate, polyketide, MVA and MEP pathways, were identified based on full-length transcriptome. Differentially expressed genes (DEGs) induced by MeJA treatment and DEGs between different tissues were identified through next-generation sequencing (NGS), revealing the genes that may be involved in the biosynthesis of anthraquinones. The basic leucine zipper (bZIP) transcription factors of R. officinale were systematically identified. Key genes such as RobZIP50 and RobZIP53 were systematically identified and found to be associated with anthraquinone biosynthesis in R. officinale through differential expression, co-expression and protein interaction analyses. RobZIP50 and RobZIP53 were highly expressed in roots and rhizomes, and significantly increased after 12 h of MeJA treatment. Additionally, both RobZIP50 and RobZIP53 were localized exclusively in the nucleus, with RobZIP53 showing significant transcriptional activity. Taken together, our results suggest that RobZIP53 may play a role in regulating anthraquinone biosynthesis in R. officinale.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

BACKGROUND: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. METHODS: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. RESULTS: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). CONCLUSION: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Association between parental educational involvement and adolescent depressive symptoms: a systematic review and meta-analysis.

BACKGROUND: Adolescents in their school-age period undergo rapid changes in various aspects, such as physiological development, academic pressure, and interpersonal relationships, constitute a high-risk group for depression. Parental educational involvement, as a critical family variable, influences not only children's academic achievement but also their psychological well-being. However, previous research has shown significant discrepancies regarding the relationship between parental educational involvement and adolescent depressive symptoms. METHODS: To elucidate the overall strength of the association between parental educational involvement and adolescent depressive symptoms, this study systematically searched Web of Science, Medline, PubMed, CNKI, and other Chinese and English databases. A meta-analysis was conducted on 22 selected studies encompassing 36 effect sizes and involving 390,094 participants. RESULTS: The results revealed a moderate negative correlation between parental educational involvement and adolescent depressive symptoms (r = -0.200, 95% CI [-0.26, -0.14]). Additionally, the relationship between parental educational involvement and adolescent depressive symptoms was found to be moderated by factors such as adolescent age, grade level and the reporter of parental educational involvement. However, it was not influenced by the female ratio or cultural background. CONCLUSIONS: This study offers the inaugural comprehensive assessment of the relationship between parental educational involvement and adolescent depressive symptoms, with variations observed across different ages, grade levels, and reporter of parental educational involvement.

Ozone therapy mitigates parthanatos after ischemic stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia-reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism. METHODS: Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SH-SY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity. RESULTS: The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos. CONCLUSIONS: These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation.

Laser-induced graphene/gold nanoparticle hybrid sensor for enhanced electrochemical detection of paracetamol.

This research presents a highly sensitive and selective electrochemical sensor for detecting paracetamol. The sensor is created using laser direct-writing on a flexible PI substrate to form LIG electrodes. Gold nanoparticles (AuNPs) are then synthesized on the working electrode through secondary laser reduction, resulting in an AuNPs/LIG composite. This combination enhances the sensor's electrochemical activity, electron transfer rate, and adsorption capacity. The sensor exhibits a linear response to paracetamol concentrations with a detection limit of 0.086 µM. Testing on Tylenol tablets and tap water showed good recovery rates. The sensor displays strong anti-interference, reproducibility, and stability, making it a promising tool for effective paracetamol monitoring in real-world situations.

Application of improved urate analysis algorithm based on spectral parameters in Podagra: A prospective study.

OBJECTIVES: To explore whether the improved urate analysis (IUA) algorithm based on spectral parameters can reduce false positives in CT gout images compared with current urate analysis (CUA) algorithm. MATERIALS AND METHODS: This prospective study was performed from May 2022 to May 2023. Spectral feet CT images of suspected gout participants were reconstructed by IUA and CUA algorithm. Qualitative diagnosis of IUA and CUA images was recorded and compared with the reference standard (ultrasound + conventional CT). Artifacts on IUA and CUA images of non-gout participants were recorded and compared; the maximum cross-sectional area of the maximum tophi (SIT-max) on IUA and CUA images of participants with gout were measured and compared. RESULTS: There are 65 participants (mean age, 43.9 years ± 13.1 [SD]; 65 men) with 114 feet studies in the gout group, and 33 participants (mean age, 43.4 years ± 15.0 [SD]; 30 men) with 65 feet studies in the non-gout group. For all 179 feet studies, IUA images had higher specificity (19.2-86.6 % vs. 1.3-44.3 %) and accuracy (63.1-88.8 % vs. 41.3-57.0 %) than CUA images (P < 0.001). In the non-gout group, the reduction rates of artifacts from the nail bed, skin, beam hardening, vascular structures, tendons, and total artifacts on the IUA images compared to the CUA images was 40.5 %, 48.9 %, 74.3 %, 99.2 %, 99.6 %, and 80.0 %, respectively (P < 0.001). For 82 feet studies with tophi, SIT-max was higher on CUA images than IUA images (P < 0.05). CONCLUSION: The improved urate analysis algorithm based on spectral parameters can reduce image artifacts and improve diagnostic efficacy.

ProT-Diff: A Modularized and Efficient Strategy for De Novo Generation of Antimicrobial Peptide Sequences by Integrating Protein Language and Diffusion Models.

Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic-resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT-Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences. ProT-Diff generates thousands of AMPs with diverse lengths and structures within a few hours. After silico physicochemical screening, 45 peptides are selected for experimental validation. Forty-four peptides showed antimicrobial activity against both gram-positive or gram-negative bacteria. Among broad-spectrum peptides, AMP_2 exhibited potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. An in vivo assessment demonstrated its effectiveness against a drug-resistant E. coli strain in acute peritonitis. This study not only introduces a viable and user-friendly strategy for de novo generation of antimicrobial peptides, but also provides potential antimicrobial drug candidates with excellent activity. It is believed that this study will facilitate the development of other peptide-based drug candidates in the future, as well as proteins with tailored characteristics.

The Preliminary Analysis of Flavonoids in the Petals of Rhododendron delavayi, Rhododendron agastum and Rhododendron irroratum Infected with Neopestalotiopsis clavispora.

The petal blight disease of alpine Rhododendron severely impacts the ornamental and economic values of Rhododendron. Plant secondary metabolites play a crucial role in resisting pathogenic fungi, yet research on metabolites in alpine Rhododendron petals that confer resistance to pathogenic fungi is limited. In the present study, the secondary metabolites in Rhododendron delavayi, R. agastum, and R. irroratum petals with anti-pathogenic activity were screened through disease index analysis, metabolomic detection, the mycelial growth rate, and metabolite spraying experiments. Disease index analysis revealed that R. delavayi petals exhibited the strongest disease resistance, while R. agastum showed the weakest, both under natural and experimental conditions. UHPLC-QTOF-MS/MS analysis identified 355 and 274 putative metabolites in positive and negative ion modes, respectively. The further antifungal analysis of differentially accumulated baicalein, diosmetin, and naringenin showed their half-inhibitory concentrations (IC50) against Neopestalotiopsis clavispora to be 5000 mg/L, 5000 mg/L, and 1000 mg/L, respectively. Spraying exogenous baicalein, diosmetin, and naringenin significantly alleviated petal blight disease caused by N. clavispora infection in alpine Rhododendron petals, with the inhibition rates exceeding 64%. This study suggests that the screened baicalein, diosmetin, and naringenin, particularly naringenin, can be recommended as inhibitory agents for preventing and controlling petal blight disease in alpine Rhododendron.

Two Peaks of Seasonal Influenza Epidemics - China, 2023.

Introduction: Influenza is a communicable respiratory disease that causes annual epidemics and occasional unpredictable pandemics. This study examines the occurrence of two unexpected influenza peaks within the year 2023. Methods: Influenza-like illness (ILI) data were reported, and specimens of ILI were collected by designated surveillance hospitals. Positive cases were confirmed using real-time reverse transcription polymerase chain reaction (rRT-PCR) testing conducted at national surveillance network laboratories. The data were then submitted to the Chinese Influenza Surveillance Information System. Results: From December 2022 to January 2023, influenza activity was minimal until a spring epidemic began in February, peaking in late March. The outbreak spread from the north to the south, with A(H1N1)pdm09 being the predominant strain and A(H3N2) also circulating concurrently. The positivity rate in northern and southern provincial-level administrative divisions (PLADs) reached 60.0% (week 10) and 60.2% (week 13), respectively, before dropping to below 5% from May to August. Subsequently, rates surged starting in week 41 in the south and week 44 in the north, peaking at 54.4% (week 50) and 44.0% (week 49), respectively, and remained high until the end of 2023. A(H3N2) became the prevailing strain, with a notable increase in B/Victoria lineage viruses from December, resulting in two peaks during the 2023 influenza season. Conclusions: The pattern of the influenza epidemic shifted due to the coronavirus disease 2019 (COVID-19) outbreak and is gradually returning to its usual seasonal and intensity patterns. It is, therefore, crucial to continuously strengthen influenza surveillance, enhance the influenza surveillance network, and lay the groundwork for advancing integrated surveillance of multiple pathogens in China.

Comparative study on metabolites, nutrients, and antioxidant capacity of endosperm in Gymnocladus chinensis, Gleditsia sinensis, and Gleditsia japonica var. delavayi.

'Zaojiaomi' is a traditional food derived from Gleditsia sinensis or Gleditsia japonica var. delavayi endosperm. However, metabolite profile of Gymnocladus chinensis endosperm and its comparison to the aforementioned species remains understudied. This research employed a UPLC-MS based metabolomics approach to investigate and compare metabolite composition of G. chinensis endosperm with that of G. sinensis and G. japonica endosperm. A total of 1177 metabolites were identified, with 579 and 577 differentially abundant metabolites found between G. chinensis vs. G. japonica and G. chinensis vs. G. sinensis, respectively. They were mainly enriched in pathways related to flavonoid biosynthesis, suggesting potential for enhanced antioxidant activity, compared to G. japonica and G. sinensis. Additionally, G. chinensis endosperm was found to be rich in L-arginine, L-aspartic acid, and zinc elements, which have various health benefits. These findings provide valuable insights into metabolic composition of G. chinensis endosperm and its potential as a functional food source.

Deciphering the role of sphingolipid metabolism in the immune microenvironment and prognosis of esophageal cancer via single-cell sequencing and bulk data analysis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer. METHODS: We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed. RESULT: Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis. CONCLUSION: This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer.

Design and synthesis of magnesium-modified copper oxide nanosheets as efficient electrocatalysts for CO2 reduction.

Electroreduction of carbon dioxide (CO2) to multiple carbon products plays a significant role in carbon neutrality and the production of valuable chemicals. Herein, we developed a magnesium-modified copper oxide nanosheet catalyst (Mg-CuO) using a post-impregnation method. Comprehensive elemental analysis demonstrated the effective incorporation of magnesium into CuO nanosheets, resulting in a noticeable alteration of the electron density of Cu atoms. Consequently, the Mg-CuO nanosheets exhibited an increased efficiency for CO2 electroreduction in comparison with the unmodified CuO nanosheets. The optimized Mg-CuO catalyst exhibited faradaic efficiencies of 46.33% for ethylene production and 62.64% for C2+ production at -1.3 V vs. reversible hydrogen electrode (RHE). DFT proved that the introduction of Mg species could increase the charge density of Cu and decrease the adsorption energy of *CO, which promoted C-C coupling and enhanced the selectivity of C2+ products. This study presents an effective way to adjust the electronic structure of common copper-based electrocatalysts and the corresponding interaction with *CO, resulting in an improved faradaic efficiency of C2+ products.

Running exercise decreases microglial activation in the medial prefrontal cortex in an animal model of depression.

BACKGROUND: Running exercise effectively ameliorates depressive symptoms in humans and depression-like behaviors in animals, but the underlying mechanisms remain unclear. Microglia-mediated neuroinflammation plays a major role in the development of depression. The medial prefrontal cortex (mPFC) is a key brain region involved in depression and is sensitive to physical activity. Whether the antidepressant effect of running exercise involves changes in mPFC microglia is not understood. METHODS: The animals were subjected to chronic unpredictable stress (CUS) intervention followed by treadmill running. The sucrose preference test and elevated plus maze test or tail suspension test were used for behavioral assessment of the animals. The number of microglia in the mPFC was quantified by immunohistochemistry and stereology. The density and morphology of microglia were analyzed via immunofluorescence staining combined with three-dimensional laser scanning techniques. The mRNA expressions of inflammatory cytokines in the mPFC were examined via quantitative real-time PCR. RESULTS: Running exercise effectively alleviated depressive-like behaviors in depression model animals. Running exercise reversed the increase in the number of microglia and the density of activated microglia in the mPFC of CUS animals. Running exercise effectively reversed the changes in microglia (reduced cell body area, total branch length and branch complexity) in the mPFC of CUS animals. Furthermore, running exercise regulated the gene expressions of pro-/antiinflammatory cytokines in the mPFC of CUS animals. CONCLUSIONS: Our results suggested that the antidepressant effects of running exercise may involve decreasing the number of activated microglia, reversing morphological changes in microglia in the mPFC, and reducing inflammatory responses.

Spatial single-cell protein landscape reveals vimentinhigh macrophages as immune-suppressive in the microenvironment of hepatocellular carcinoma.

Tumor microenvironment heterogeneity in hepatocellular carcinoma (HCC) on a spatial single-cell resolution is unclear. Here, we conducted co-detection by indexing to profile the spatial heterogeneity of 401 HCC samples with 36 biomarkers. By parsing the spatial tumor ecosystem of liver cancer, we identified spatial patterns with distinct prognosis and genomic and molecular features, and unveiled the progressive role of vimentin (VIM)high macrophages. Integration analysis with eight independent cohorts demonstrated that the spatial co-occurrence of VIMhigh macrophages and regulatory T cells promotes tumor progression and favors immunotherapy. Functional studies further demonstrated that VIMhigh macrophages enhance the immune-suppressive activity of regulatory T cells by mechanistically increasing the secretion of interleukin-1ß. Our data provide deep insights into the heterogeneity of tumor microenvironment architecture and unveil the critical role of VIMhigh macrophages during HCC progression, which holds potential for personalized cancer prevention and drug discovery and reinforces the need to resolve spatial-informed features for cancer treatment.

Triple-crosslinked double-network alginate/dextran/dendrimer hydrogel with tunable mechanical and adhesive properties: A potential candidate for sutureless keratoplasty.

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.

Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.

Corneal diseases represent 5.1% of all eye defects and are the fourth leading cause of blindness globally. Corneal neovascularization can arise from all conditions of chronic irritation or hypoxia, which disrupts the immune-privileged state of the healthy cornea, increases the risk of rejection after keratoplasty, and leads to opacity. In the past decades, significant progress has been made for neovascular diseases of the retina and choroid, with plenty of drugs getting commercialized. In addition, to overcome the barriers of the short duration and inadequate penetration of conventional formulations of antivascular endothelial growth factor (VEGF), multiple novel drug delivery systems, including adeno-associated virus (AAV)-mediated transfer have gone through the full process of bench-to-bedside translation. Like retina neovascular diseases, corneal neovascularization also suffers from chronicity and a high risk of recurrence, necessitating sustained and efficient delivery across the epithelial barrier to reach deep layers of the corneal stroma. Among the explored methods, adeno-associated virus-mediated delivery of anti-VEGF to treat corneal neovascularization is the most extensively researched and most promising strategy for clinical translation although currently although, it remains predominantly at the preclinical stage. This review comprehensively examines the necessity, benefits, and risks of applying AAV vectors for anti-VEGF drug delivery in corneal vascularization, including its current progress and challenges in clinical translation.