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.

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.

Comparative study of CTA/CTV and MRTA for preoperative simulation of microvascular decompression in neurovascular compression syndromes.

Neurovascular compression syndrome (NVCS), characterized by cranial nerve compression due to adjacent blood vessels at the root entry zone, frequently presents as trigeminal neuralgia (TN), hemifacial spasm (HFS), or glossopharyngeal neuralgia (GN). Despite its prevalence in NVCS assessment, Magnetic Resonance Tomographic Angiography (MRTA)'s limited sensitivity to small vessels and veins poses challenges. This study aims to refine vessel localization and surgical planning for NVCS patients using a novel 3D multimodal fusion imaging (MFI) technique incorporating computed tomography angiography and venography (CTA/CTV). A retrospective analysis was conducted on 76 patients who underwent MVD surgery and were diagnosed with single-site primary TN, HFS, or GN. Imaging was obtained from MRTA and CTA/CTV sequences, followed by image processing and 3D-MFI using FastSurfer and 3DSlicer. The CTA/CTV-3D-MFI showed higher sensitivity than MRTA-3D-MFI in predicting responsible vessels (98.6% vs. 94.6%) and NVC severity (98.6% vs. 90.8%). Kappa coefficients revealed strong agreement with MRTA-3D-MFI (0.855 for vessels, 0.835 for NVC severity) and excellent agreement with CTA/CTV-3D-MFI (0.951 for vessels, 0.952 for NVC). Resident neurosurgeons significantly preferred CTA/CTV-3D-MFI due to its better correlation with surgical reality, clearer depiction of surgical anatomy, and optimized visualization of approaches (p < 0.001). Implementing CTA/CTV-3D-MFI significantly enhanced diagnostic accuracy and surgical planning for NVCS, outperforming MRTA-3D-MFI in identifying responsible vessels and assessing NVC severity. This innovative imaging modality can potentially improve outcomes by guiding safer and more targeted surgeries, particularly in cases where MRTA may not adequately visualize crucial neurovascular structures.

Unveiling the spin evolution in van der Waals antiferromagnets via magneto-exciton effects.

Among the fascinating phenomena observed in two-dimensional (2D) magnets, the magneto-exciton effect stands out as a pivotal link between optics and magnetism. Although the excitonic effect has been revealed and exhibits a considerable correlation with the spin structures in certain 2D magnets, the underlying mechanism of the magneto-exciton effect remains underexplored, especially under high magnetic fields. Here we perform a systematic investigation of the spin-exciton coupling in 2D antiferromagnetic NiPS3 under high magnetic fields. When an in-plane magnetic field is applied, the exceptional sharp excitonic emission at ~1.4756 eV exhibits a Zeeman-like splitting with g ≈ 2.0, experimentally identifying the exciton as an excitation of dominant triplet-singlet character. By examining the polarization of excitonic emission and simulating the spin evolution, we further verify the correlation between excitonic emission and Néel vector in NiPS3. Our work elucidates the mechanism behind the spin-exciton coupling in NiPS3 and establishes a strategy for optically probing the spin evolutions in 2D magnets.

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.

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.

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.

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.

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.

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.

Maternal riboflavin deficiency causes embryonic defects by activating ER stress-induced hepatocyte apoptosis pathway.

Riboflavin deficiency (RD) induces liver damage, abnormal embryonic development, and high mortality. We hypothesized that the phenotype could be rescued by inhibiting ER stress. The objectives of the present study were to investigate the underlying molecular mechanisms of RD-induced embryonic defects using in vitro and in vivo models. Primary duck embryonic hepatocytes were treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, and cultured in RD medium and riboflavin-sufficient (CON) medium for 8 days. Laying ducks (n = 20 cages/diet, 1 bird/cage) were fed an RD diet or CON diet for 14 wk, and the eggs were collected for hatching. At day 7 of incubation, the fertilized RD eggs were injected with or without 4-PBA into the yolk. RD decreased cell number and cell viability compared to the CON group, induced oxidative stress and apoptosis in primary duck embryonic hepatocytes. However, after being treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, the apoptosis rate in RD hepatocytes decreased by 60.6 % and 86.1 %, respectively, being equal to the CON. These results indicated that RD-induced hepatocyte apoptosis is mediated by ER stress and the CHOP pathway. In vivo, RD embryos showed low hatchability, abnormal development, liver damage, ER stress, and apoptosis compared to the CON group. However, 4-PBA administration, as a model of ER stress inhibition, substantially restored embryonic development and alleviated liver damage in the RD group, including ER stress and apoptosis. Notably, hatchability in the RD group increased from 21.7 % to 72.7 % after 4-PBA treatment, though it remained less than the CON group (87.7 %). These results implicated ER stress-CHOP-apoptosis pathway as molecular mechanisms underlying RD-induced abnormal embryonic development and death, this target with potential for therapy or intervention.

Evaluating the relative importance of predictors in Generalized Additive Models using the gam.hp R package.

Generalized Additive Models (GAMs) are widely employed in ecological research, serving as a powerful tool for ecologists to explore complex nonlinear relationships between a response variable and predictors. Nevertheless, evaluating the relative importance of predictors with concurvity (analogous to collinearity) on response variables in GAMs remains a challenge. To address this challenge, we developed an R package named gam.hp. gam.hp calculates individual R 2 values for predictors, based on the concept of 'average shared variance', a method previously introduced for multiple regression and canonical analyses. Through these individual R 2s, which add up to the overall R 2, researchers can evaluate the relative importance of each predictor within GAMs. We illustrate the utility of the gam.hp package by evaluating the relative importance of emission sources and meteorological factors in explaining ozone concentration variability in air quality data from London, UK. We believe that the gam.hp package will improve the interpretation of results obtained from GAMs.

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.

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.

Efficacy and safety of anlotinib as maintenance therapy in patients with advanced non-small cell lung cancer achieving SD post first-line chemotherapy combined with immunotherapy.

Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.

Analysis of the influential factors on innovative behaviors among ophthalmic specialty nurses in China: a cross-sectional study.

OBJECTIVE: To investigate the current situation of innovative behavior and organizational structure authorization of ophthalmic specialty nurses in China, and analyze the influencing factors of innovative behavior. METHODS: A cross-sectional survey was carried out among 301 ophthalmic specialty nurses in China, representing Representing 82 hospitals in 25 provinces, using a general data questionnaire, Innovative Behavior Scale(IBS), and conditions of work effectiveness questionnaire(CWEQ-II). RESULTS: The mean total score for innovative behavior among Chinese ophthalmic specialty nurses was (4.73 ± 1.14), and the mean total score for organizational structure authorization was (61.65 ± 14.69). The logistic regression analysis revealed that organizational structure authorization, hospital grade, and ophthalmic specialty nurses primarily engaged in clinical care and clinical research had statistically significant impacts on the level of innovative behavior (P < 0.05). The higher the organizational structure authorization score, the higher the innovative behavior level of ophthalmic specialty nurses, the level of innovation behavior of grade-B tertiary hospitals is higher than that of grade-A tertiary hospitals. The main positions are low level of innovative behavior in clinical care and high level of innovative behavior in clinical research. CONCLUSIONS: The innovative behavior and organizational structure authorization of Chinese ophthalmic specialty nurses are at a medium level, the innovative behavior of ophthalmic specialty nurses is influenced by factors such as organizational structure empowerment level, hospital grade, and main job position. Nursing managers are advised to develop tailored training programs based on the influencing factors of innovative behavior among Chinese ophthalmic specialty nurses, in order to enhance their level of innovation and improve the quality of nursing services provided by Chinese ophthalmic specialty nurses.

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.

Enhancing the therapeutic potential of P29 protein-targeted monoclonal antibodies in the management of alveolar echinococcosis through CDC-mediated mechanisms.

Alveolar echinococcosis (AE) is a highly lethal helminth infection. Current chemotherapeutic strategies for AE primarily involve the use of benzimidazoles (BZs) such as mebendazole (MDZ) and albendazole (ABZ), which exhibit limited efficacy. In a previous study, the vaccine of recombinant Echinococcus granulosus P29 (rEgP29) showed significant immunoprotection against E. granulosus in both mice and sheep. In the current study, we utilized hybridoma technology to generate five monoclonal antibodies (mAbs) against P29, among which 4G10F4 mAb exhibited the highest antigen-specific binding capacity. This mAb was selected for further investigation of anti-AE therapy, both in vivo and in vitro. In vitro, 4G10F4 inhibited a noteworthy inhibition of E. multilocularis protoscoleces and primary cells viability through complement-dependent cytotoxicity (CDC) mechanism. In vivo, two experiments were conducted. In the first experiment, mice were intraperitoneally injected with Em protoscoleces, and subsequently treated with 4G10F4 mAb (2.5/5/10 mg/kg) at 12 weeks postinfection once per week for 8 times via tail vein injection. Mice that were treated with 4G10F4 mAb only in dosage of 5mg/kg exhibited a significant lower mean parasite burden (0.89±0.97 g) compared to isotype mAb treated control mice (2.21±1.30 g). In the second experiment, mice were infected through hepatic portal vein and treated with 4G10F4 mAb (5mg/kg) at one week after surgery once per week for 8 times. The numbers of hepatic metacestode lesions of the 4G10F4 treatment group were significantly lower in comparison to the isotype control group. Pathological analysis revealed severe disruption of the inner structure of the metacestode in both experiments, particularly affecting the germinal and laminated layers, resulting in the transformation into infertile vesicles after treatment with 4G10F4. In addition, the safety of 4G10F4 for AE treatment was confirmed through assessment of mouse weight and evaluation of liver and kidney function. This study presents antigen-specific monoclonal antibody immunotherapy as a promising therapeutic approach against E. multilocularis induced AE.

Assessment of the Corneal Biomechanical Features of Sturge-Weber Syndrome Using Dynamic Ultrahigh-speed Scheimpflug Imaging.

PURPOSE: To evaluate the corneal biomechanical characteristics of eyes with Sturge-Weber syndrome (SWS) secondary glaucoma (SSG) by analyzing corneal biomechanical parameters obtained using the Corneal Visualization Scheimpflug Technology instrument (Corvis ST). METHODS: In patients with SWS, eyes affected by SSG were designated as the SSG group while the contralateral eyes were designated as the SWS contralateral group (SC group). Patients from the myopia clinic served as the control group. Dynamic corneal response parameters (DCRs) including the stress-strain index (SSI)-a critical material stiffness parameter that excludes interference from IOP and central corneal thickness (CCT)-were analyzed. RESULTS: For CCT, no significant difference was observed between the SSG and SC groups. However, significant differences were found between the SSG and control groups and between the SC and control groups. Parameters such as HC Time, A1 Deformation Amp., A2 Deformation Amp., length of Whole Eye Movement (WEM), DA Ratio Max (2 mm), PachySlope, DA Ratio Max (1 mm), and ARTh showed significant differences between the SSG group and control group. In the SSG group, 4 of night eyes had an SSI of less than 0.85. CONCLUSIONS: Some DCRs indicated a stiffer cornea in the SSG group, possibly due to a thicker cornea in this group. On analyzing SSI, it was found that corneal material properties change, becoming less stiff in some of the patients with SSG. In conclusion, our study provides a preliminary exploration of the biomechanical properties of SWS secondary glaucoma.