Transcriptomic and functional analyzes reveal that the brassinosteroid insensitive 1 receptor (OsBRI1) regulates cold tolerance in rice.

Brassinosteroids (BR) play crucial roles in plant development and abiotic stresses in plants. Exogenous application of BR can significantly enhance cold tolerance in rice. However, the regulatory relationship between cold tolerance and the BR signaling pathway in rice remains largely unknown. Here, we characterized functions of the BR receptor OsBRI1 in response to cold tolerance in rice using its loss-of-function mutant (d61-1). Our results showed that mutant d61-1 was less tolerant to cold stress than wild-type (WT). Besides, d61-1 had lower levels than WT for some physiological parameters, including catalase activity (CAT), superoxide dismutase activity (SOD), peroxidase activity (POD), peroxidase activity (PRO), soluble protein, and soluble sugar content, while malondialdehyde content (MDA) and relative electrical conductivity (REC) levels in d61-1 were higher than those in WT plants. These results indicated that the loss of OsBRI1 function resulted in decreased cold tolerance in rice. In addition, we performed RNA sequencing (RNA-seq) of WT and d61-1 mutant under cold stress. Numerous common and unique differentially expressed genes (DEGs) with up- and down-regulation were observed in WT and d61-1 mutant. Some DEGs were expressed to various degrees, even opposite, between CK1 vs. T1 (WT) and CK2 vs. T2 (d61-1). Among these specific DEGs, some typical genes are involved in plant tolerance to cold stress. Through weighted correlation network analysis (WGCNA), 50 hub genes were screened in the turquoise and blue module. Many genes were involved in cold stress and plant hormone, such as Os01g0279800 (BRI1-associated receptor kinase 1 precursor), Os10g0513200 (Dwarf and tiller-enhancing 1, DTE1), Os02g0706400 (MYB-related transcription factor, OsRL3), etc. Differential expression levels of some genes were verified in WT and d61-1 under cold stress using qRT-PCR. These valuable findings and gene resources will be critical for understanding the regulatory relationships between cold stress tolerance and the BR signaling pathways in rice.

Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.

An environmentally-friendly permeable liquid salt pyrolysis method based on capillary heat transfer for recycling waste insulator materials.

Molten salt pyrolysis technology stands out as a potent approach for achieving efficient degradation and energy recovery of composite organic materials. Nevertheless, challenges such as the high melting point of molten salt, product destruction, and the complexities of treating waste salt pose significant limitations to the widespread application and popularization of this technology. To tackle these issues, this study proposes a salt-assisted pyrolysis method based on capillary heat transfer called permeable liquid salt pyrolysis. Focusing on abandoned power industry insulators, the research delves into the thermal and mass transfer model of cluster-embedded materials under non-molten salt conditions. The investigation reveals that the capillary between glass fiber and resin proves beneficial in enhancing heat transfer conditions by creating a novel phase known as permeate liquid. Results demonstrate that salt-assisted pyrolysis can substantially lower the required temperature and enhance the pyrolysis reaction rate, achieving a maximum degradation efficiency of 98.99 %. Additionally, the pyrolysis products undergo in-situ modification, with a notable reduction in benzene series compounds ranging from 68 % to 85 %. Furthermore, an erosion diffusion capillary mode is established. This study presents an environmentally-friendly approach to recycle and modify products derived from waste resin-based composite materials generated in the electric power industry.

The Therapeutic Role and Mechanism of Glabridin Under Aspergillus fumigatus Infection.

Purpose: To characterize the efficiency of glabridin alone and in combination with clinical antifungals in Aspergillus fumigatus keratitis. Methods: The broth microdilution method was performed to investigate whether glabridin exerted an antifungal role on planktonic cells and immature and mature biofilm. Antifungal mechanism was evaluated by Sorbitol and Ergosterol Assays. The synergistic effect of glabridin and antifungals was assessed through the checkerboard microdilution method and time-killing test. Regarding anti-inflammatory role, inflammatory substances induced by A. fumigatus were assessed by real-time quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Drug toxicity was assessed by Draize test in vivo. Macrophage phenotypes were examined by flow cytometry. Results: Regarding antifungal activity, glabridin destroyed fungal cell wall and membrane on planktonic cells and suppressed immature and mature biofilm formation. After combining with natamycin or amphotericin B, glabridin possessed a potent synergistic effect against A. fumigatus. Regarding anti-inflammatory aspects, Dectin-1, toll­like receptor (TLR)-2 and TLR-4 expression of human corneal epithelial cells were significantly elevated after A. fumigatus challenge and reduced by glabridin. The elevated expression of interleukin-1ß and tumor necrosis factor-alpha induced by A. fumigatus or corresponding agonists were reversed by glabridin, equivalent to the effect of corresponding inhibitors. Glabridin could also contribute to anti-inflammation by downregulating inflammatory mediator expression to suppress macrophage infiltration. Conclusions: Glabridin contributed to fungal clearance by destroying fungal cell wall and membrane, and disrupting biofilm. Combining glabridin with clinical antifungals was superior in reducing A. fumigatus growth. Glabridin exerted an anti-inflammatory effect by downregulating proinflammatory substance expression and inhibiting macrophage infiltration, which provide a potential agent and treatment strategies for fungal keratitis.

Pollution characteristics and release mechanism of microplastics in a typical end-of-life vehicle (ELV) recycling base, East China.

Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.

Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach.

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.

A green strategy for upcycling utilization of core parts from end-of-life vehicles (ELVs): Pollution source analysis, technology flowchart, technology upgrade.

The disposal of end-of-life vehicles (ELVs) is an issue of great concern to the society, because of its huge amount, resource value and environmental pollution. A wide variety of pollutants generate and release during the recycling process. However, previous studies are piecemeal and segmentary, the correlation between treatment flowchart and pollution is unknown, and pollution source analysis in ELV recycling and core parts (engine, gear box, etc.) remanufacturing bases is still a challenge. In this study, the aim is to propose a green strategy for upcycling utilization of ELV part based on pollution source analysis, technology flowchart, and technology upgrade. We synthetically analyzed current typical ELV dismantling and core part remanufacturing processes of ELVs. A total of 36 volatile organic compound (VOC) species and 7 heavy metals were found in dismantling process, and 61 VOC species were detected in remanufacturing process. Based on statistical analysis and treatment process characteristics, 18 pollution fingerprints were constructed. At last, an intelligent dismantling and upcycle utilization line for ELVs has been developed to improve production efficiency and reduce pollution release.

Enhancing Debromination Efficiency through Introducing Water Vapor Atmosphere to Overcome Limitations of Conventional Pyrolysis.

Bromine removal is significant in the recycling of waste printed circuit boards (WPCBs). This study found that the critical factors limiting the debromination efficiency of conventional pyrolysis are the formation of coke impeding mass transfer and conversion of bromine into less volatile species, such as coking-Br and copper bromide. According to frontier molecular orbital analysis and thermodynamic equilibrium analysis, C-O bonds of resin are sites prone to electrophilic reactions and copper bromide in residue may undergo hydrolysis; therefore, introducing H2O during pyrolysis was a feasible method for thorough debromination. Through pyrolysis in a water vapor atmosphere, the diffusion limitation of debromination was overcome, and resin was converted into light components; thereby, rapid and deep removal of bromine was achieved. The result indicated that 99.7% of bromine was removed, and the residue could be used as a clean secondary resource. According to life-cycle assessment, pyrolysis of WPCBs in water vapor could be expected to reduce 77 Kt of CO2 emission and increase financial benefits by 60 million dollars, annually.

Quercetin protects against Aspergillus fumigatus keratitis by reducing fungal load and inhibiting TLR-4 induced inflammatory response.

PURPOSE: To investigate the antifungal and anti-inflammatory effects of quercetin in Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: Draize eye test was performed in mice to evaluate the toxicity of quercetin, and the antifungal effects on A. fumigatus were assessed via scanning electron microscopy (SEM), propidium iodide uptake, and adherence assay. In fungal keratitis (FK) mouse models, immunostaining was performed for investigating toll-like receptor 4 (TLR-4) expression and macrophage infiltration. Real-time PCR, ELISA, and Western blot were used to evaluate the expression of pro-inflammatory factors IL-1ß, TNF-α, and IL-6 in infected RAW264.7 cells. Cells were also treated with TLR-4 siRNA or agonist CRX-527 to investigate mechanisms underlying the anti-inflammatory activity of quercetin. RESULTS: Quercetin at 32 µM was non-toxic to corneal epithelial and significantly inhibited A. fumigatus growth and adhesion, and also altered the structure and reduced the number of mycelia. Quercetin significantly reduced macrophage infiltration in the mouse cornea, and attenuated the expression of TLR-4 in the corneal epithelium and stroma of mice with keratitis caused by A. fumigatus. In RAW264.7 cells infected by A. fumigatus, quercetin downregulated TLR-4 along with pro-inflammatory factors IL-1ß, TNF-α, and IL-6. RAW cells with TLR-4 knockdown had reduced expression of factors after A. fumigatus infection, which was decreased even further with quercetin treatment. In contrast, cells with CRX-527 had elevated inflammatory factors compared to control, which was significantly attenuated in the presence of quercetin. CONCLUSION: Quercetin plays a protective role in mouse A. fumigatus keratitis by inhibiting fungal load, disrupting hyphae structure, macrophage infiltration, and suppressing inflammation response in macrophages via TLR-4 mediated signaling pathway.

Research on compound pollution characteristics and health risk evaluation of particulate matter and heavy metals in waste glass recycling process.

Owing to the large amount of waste glass generated, the waste glass recycling base is an indispensable municipal supporting facility of a sustainable city. However, waste glass recycling is a complex process involving stages such as multiple-stage crushing and material sorting. Consequently, waste glass recycling base has a considerable impact on the surrounding environment, such as health risk of particulate matter on workers. In this study, we aimed to perform a comprehensive investigation and analysis of compound pollution characteristics and health risk evaluation of particulate matter and heavy metals generated from waste glass recycling process. Soil, particulate fallout, and glass samples were collected from inside and outside a recycling plant in eastern China. Our findings showed that the waste glass treatment process produces a large amount of air particulate matter, and the PM2.5 and PM10 concentrations can reach 3725 and 4055 µg/m3, respectively, in the production workshop during working hours. Meanwhile, the monitoring results show that the concentration of heavy metals on fine particles is higher compared to coarse particles. The high Zn and Pb concentrations detected in the soil and dustfall were proved to be derived from the glass raw materials. However, health risk assessment and particle deposition modeling in the human respiratory system revealed that heavy metals from the air particulate matter have no significant carcinogenicity or non-carcinogenic risk. The Gaussian dispersion model showed that the impact of particulate matter on the surrounding environment and health of the surrounding residents is minimal. Furthermore, transportation is the major emission link according to the particulate emission calculation, indicating that it is imperative to upgrade and reform the existing processes of waste glass recycling. Taken together, this study provides a scientific basis for the green development of waste glass recycling process and further environmental information regarding waste glass recycling plants.

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action.

Colorectal cancer (CRC) is the third most common malignant tumor in the world, and it is prone to recurrence and metastasis during treatment. Aerobic glycolysis is one of the main characteristics of tumor cell metabolism in CRC. Tumor cells rely on glycolysis to rapidly consume glucose and to obtain more lactate and intermediate macromolecular products so as to maintain growth and proliferation. The regulation of the CRC glycolysis pathway is closely associated with several signal transduction pathways and transcription factors including phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), myc, and p53. Targeting the glycolytic pathway has become one of the key research aspects in CRC therapy. Many phytochemicals were shown to exert anti-CRC activity by targeting the glycolytic pathway. Here, we review the effects and mechanisms of phytochemicals on CRC glycolytic pathways, providing a new method of drug development.

ß3GNT9 as a prognostic biomarker in glioblastoma and its association with glioblastoma immune infiltration, migration and invasion.

Background: Studies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of ß1,3-N-acetylglucosaminyltransferase-9 (ß3GNT9) in the progression of glioblastoma, this study identifies the value of ß3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between ß3GNT9 expression and glioblastoma immune infiltration, migration and invasion. Methods: ß3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between ß3GNT9 expression and clinical features was analyzed. The relationship between ß3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of ß3GNT9 in glioblastoma. The correlation between ß3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify ß3GNT9 expression in vitro. The effects of ß3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays. Results: ß3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (P<0.05). The overall survival rate in high ß3GNT9 expression group was significantly lower than that in low ß3GNT9 expression group (P<0.05). Regression analyses suggested that ß3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that ß3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that ß3GNT9 was highly expressed in A172, U87MG and U251 cell lines (P<0.05), and promoted the migration and invasion of glioblastoma (P<0.05). Conclusion: The increased expression of ß3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. ß3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.

A comprehensive analysis on the source-exposure and diffusion rule of VOCs for end-life vehicles dismantling activities.

In recent years, the rapid development of technology has posed significant challenges to the waste management practices of the retired vehicle industry. How to minimize the environmental impact during the recycle process of scrap vehicle has emerged as a prevalent and pressing concern. This study employed statistical analysis and positive matrix factorization (PMF) model to assess the origin of Volatile Organic Compounds (VOCs) at a scrap vehicle dismantling location situated in China. The quantification of potential hazards to human health arising from identified sources was achieved through the integration of source characteristics with exposure risk assessment. In addition, fluent simulation was employed to examine the spatiotemporal dispersion of the pollutant concentration field and velocity profile. The findings of the study revealed that the activities of parts cutting, disassembling air conditioning and refined dismantling were responsible for 89.98 %, 84.36 %, and 78.63 % of the total air pollution accumulation, respectively. Additionally, it should be noted that the aforementioned sources accounted for 59.40 %, 18.44 %, and 4.86 % of the aggregate non-cancer risk. The cumulative cancer risk was determined to be the disassembling air conditioning process, with a contribution of 82.71 %. Meanwhile, the average concentration of VOC in soil around the disassembling air conditioning area is 8.4 times higher than the background value. The simulation revealed that pollutants were primarily dispersed within the factory at a height ranging from 0.75 m to 2 m, which corresponds to the human respiratory zone and the concentration of pollutants in the vehicle cutting area was observed to exceed normal levels by over 10 times. These findings of this study may serve as a foundation for improving of environmental protection measures of industrialization.

Demand prediction of medical services in home and community-based services for older adults in China using machine learning.

Background: Home and community-based services are considered an appropriate and crucial caring method for older adults in China. However, the research examining demand for medical services in HCBS through machine learning techniques and national representative data has not yet been carried out. This study aimed to address the absence of a complete and unified demand assessment system for home and community-based services. Methods: This was a cross-sectional study conducted on 15,312 older adults based on the Chinese Longitudinal Healthy Longevity Survey 2018. Models predicting demand were constructed using five machine-learning methods: Logistic regression, Logistic regression with LASSO regularization, Support Vector Machine, Random Forest, and Extreme Gradient Boosting (XGboost), and based on Andersen's behavioral model of health services use. Methods utilized 60% of older adults to develop the model, 20% of the samples to examine the performance of models, and the remaining 20% of cases to evaluate the robustness of the models. To investigate demand for medical services in HCBS, individual characteristics such as predisposing, enabling, need, and behavior factors constituted four combinations to determine the best model. Results: Random Forest and XGboost models produced the best results, in which both models were over 80% at specificity and produced robust results in the validation set. Andersen's behavioral model allowed for combining odds ratio and estimating the contribution of each variable of Random Forest and XGboost models. The three most critical features that affected older adults required medical services in HCBS were self-rated health, exercise, and education. Conclusion: Andersen's behavioral model combined with machine learning techniques successfully constructed a model with reasonable predictors to predict older adults who may have a higher demand for medical services in HCBS. Furthermore, the model captured their critical characteristics. This method predicting demands could be valuable for the community and managers in arranging limited primary medical resources to promote healthy aging.

Honokiol reduces fungal burden and ameliorate inflammation lesions of Aspergillus fumigatus keratitis via Dectin-2 down-regulation.

PURPOSE: To screen and identify the mechanism of honokiol on anti-fungi and anti-inflammation in fungal keratitis (FK) through bioinformatic analysis and biological experiments. METHODS: Transcriptome profile demonstrated differential expression genes (DEGs) of Aspergillus fumigatus keratitis between PBS-treated and honokiol-treated groups via bioinformatics analyses. Inflammatory substances were quantified by qRT-PCR, Western blot and ELISA, and macrophage polarization was examined by flow cytometry. Periodic acid Schiff staining and morphological interference assay were used to detect hyphal distribution in vivo and fungal germination in vitro, respectively. Electron microscopy was to illustrate hyphal microstructure. RESULTS: Illumina sequencing demonstrated that compared with the honokiol group, 1175 up-regulated and 383 down-regulated genes were induced in C57BL/6 mice Aspergillus fumigatus keratitis with PBS treatment. Through GO analysis, some differential expression proteins (DEPs) played major roles in biological processes, especially fungal defense and immune activation. KEGG analysis provided fungus-related signaling pathways. PPI analysis demonstrated that DEPs from multiple pathways form a close-knit network, providing a broader context for FK treatment. In biological experiments, Dectin-2, NLRP3 and IL-1ß were upregulated by Aspergillus fumigatus to evaluate immune response. Honokiol could reverse the trend, comparable to Dectin-2 siRNA interference. Meanwhile, honokiol could also play an anti-inflammatory role via promoting M2 phenotype polarization. Moreover, honokiol reduced hyphal distribution in the stroma, delayed germination, and destroyed the hyphal cell membrane in-vitro. CONCLUSIONS: Honokiol possesses anti-fungal and anti-inflammatory effects in Aspergillus fumigatus keratitis and may develop a potential and safe therapeutic modality for FK.

Anti-CD47 Antibody Enhances the Efficacy of Chemotherapy in Patients with Gastric Cancer Liver Metastasis.

Patients with gastric cancer liver metastasis (GCLM) are often treated with palliative care, and they show a poor prognosis. In gastric cancer, high CD47 expression has been shown to indicate a poor prognosis. CD47, expressed on the cell surface, prevents the cells from being phagocytosed by macrophages. Anti-CD47 antibodies have been shown to be effective in the treatment of metastatic leiomyosarcoma. Nonetheless, the role of CD47 in GCLM has not yet been elucidated. Here, we showed that CD47 expression in GCLM tissues was higher than that in situ. Moreover, we demonstrated that high CD47 expression correlated with an adverse prognosis. Accordingly, we investigated the role of CD47 in the development of GCLM in mouse liver. Knockdown of CD47 inhibited GCLM development. Furthermore, in vitro engulfment assays showed that decreased CD47 expression led to an increased phagocytic activity of Kupffer cells (KCs). Using enzyme-linked immunosorbent assay, we determined that CD47 knockdown promoted cytokine secretion by macrophages. Furthermore, we found that tumor-derived exosomes decreased KC-mediated phagocytosis of gastric cancer cells. Finally, in a heterotopic xenograft model, the administration of anti-CD47 antibodies inhibited tumor growth. In addition, as 5-fluorouracil (5-Fu)-based chemotherapy is the cornerstone in GCLM treatment, we administered a combination of anti-CD47 antibodies and 5-Fu, which acted synergistically to suppress the tumor. Overall, we demonstrated that tumor-derived exosomes are involved in GCLM progression, targeting CD47 inhibits gastric cancer tumorigenesis, and a combination of anti-CD47 antibodies and 5-Fu shows potential for treating GCLM.

Debromination with Bromine Recovery from Pyrolysis of Waste Printed Circuit Boards Offers Economic and Environmental Benefits.

Bromine is an important resource that is widely used in medical, automotive, and electronic industries. Waste electronic products containing brominated flame retardants can cause serious secondary pollution, which is why catalytic cracking, adsorption, fixation, separation, and purification have gained significant attention. However, the bromine resources have not been effectively reutilized. The application of advanced pyrolysis technology could help solve this problem via converting bromine pollution into bromine resources. Coupled debromination and bromide reutilization during pyrolysis is an important field of research in the future. This prospective paper presents new insights in terms of the reorganization of different elements and adjustment of bromine phase transition. Furthermore, we proposed some research directions for efficient and environmentally friendly debromination and reutilization of bromine: 1) precise synergistic pyrolysis should be further explored for efficient debromination, such as using persistent free radicals in biomass, polymer hydrogen supply, and metal catalysis, 2) rematching of Br elements and nonmetal elements (C/H/O) will be a promising direction for synthesizing functionalized adsorption materials, 3) oriented control of the bromide migration path should be further studied to obtain different forms of bromine resources, and 4) advanced pyrolysis equipment should be well developed.

Optimal time point for neutrophil-to-lymphocyte ratio to predict stroke-associated pneumonia.

PURPOSE: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). METHODS: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24-36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. RESULTS: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123-1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017-1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. CONCLUSION: Increased NLR measured within 24-36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality.

Glabridin Inhibits Aspergillus fumigatus Growth and Alleviate Inflammation Mediated by Dectin-2 and NLRP3 Inflammasome.

PURPOSE: The research was used to uncover the mechanism of glabridin in Aspergillus fumigatus keratitis in anti-fungus and anti-inflammation. METHODS: In vitro, RAW 264.7 cells were infected with A. fumigatus with incubation of glabridin in different concentrations. Real-time quantitative polymerase chain reaction (RT­qPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were used to assess the inflammatory severe and alternation with the intervention of Dectin-2 siRNA and glabridin. In vivo, A. fumigatus keratitis mouse models were established by spore intra-stromal injection and treated with glabridin or PBS. And disease scores, inflammatory mediators, and periodic acid-schiff (PAS) staining were exhibited to demonstrate the therapeutic efficiency of glabridin in vivo. Morphological interference assay monitored fungal germination. Scanning and transmission electron microscopy were used to observe the growth of fungi. RESULTS: In RAW 264.7 cells and mouse keratitis models, noncytotoxic 16 µg/mL glabridin showed significant inhibition in the expression of Dectin-2, NLRP3, Caspase-1, IL-1ß, and TNF-α after A. fumigatus infection, almost similar to the intervention of Dectin-2 siRNA. PAS staining illustrated the reduced hyphal distribution in cornea stroma with glabridin treatment. Glabridin remarkably inhibited A. fumigatus growth through delaying germination and disrupting the integrity of the hyphae membrane. CONCLUSION: Glabridin plays an anti-inflammatory role in A. fumigatus challenge via suppression of the Dectin-2 and NLRP3 inflammasome, and plays an anti-fungal role through delaying germination and changing the hyphal integrity.KEY MESSAGESGlabridin plays an anti-inflammatory role in A. fumigatus infection of RAW264.7 cells in a concentration-dependent manner and through Dectin-2 mediation.Glabridin decreases fungal distribution and inflammation in mouse A. fumigatus keratitis.Glabridin inhibits A. fumigatus growth by delaying germination and disrupting cellular structure in vitro.

Gallic Acid Ameliorates Aspergillus Fumigatus Keratitis Through Reducing Fungal Load and Suppressing the Inflammatory Response.

Purpose: The purpose of this study was to explore the antifungal and anti-inflammatory effects of gallic acid (GA) on Aspergillus fumigatus (A. fumigatus) keratitis. Methods: CCK-8 assay and Draize eye test were used to determine the non-cytotoxic concentration of GA in RAW264.7 cells and an A. fumigatus keratitis mouse model. The antifungal effects of GA were analyzed using minimal inhibitory concentration (MIC), biofilm formation test, fungal adherence assay, calcofluor white staining, and propidium iodide staining. The therapeutic effects of GA were estimated by slit lamp photographs, clinical score, hematoxylin and eosin (H&E) staining, and Periodic acid-Schiff staining in vivo. Immunofluorescence staining and myeloperoxidase assay were conducted to identify neutrophil infiltration and activity. RT-PCR, ELISA, and Western blot were performed to detect the expression of pro-inflammatory cytokines and Nrf2/HO-1. Results: In HCECs and A. fumigatus keratitis mouse model, GA at 100 µg/mL did not affect cell viability, thus this concentration was applied to subsequent experiments. In vitro, GA significantly inhibited A. fumigatus growth, biofilm formation, and adhesion. In vivo, 100 µg/mL GA alleviated the severity of fungal keratitis (FK) by repressing fungal load, reducing neutrophil infiltration, and lowering MPO activity. Besides, the expression of IL-1ß, TNF-α, LOX-1, and COX-2 was inhibited, whereas Nrf2 and HO-1 expression was enhanced at both mRNA and protein levels in the 100 µg/mL GA treated group in comparison to PBS control. Conclusions: GA ameliorates FK severity through inhibiting A. fumigatus load, reducing neutrophils infiltration, downregulating the expression of pro-inflammatory cytokines, and enhancing the Nrf2/HO-1 pathway, which provides new insight into A. fumigatus keratitis treatment.