A multifunctional ionic liquid coating on 3D-Printed prostheses: Combating infection, promoting osseointegration.

Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway.

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 µg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 µg. Antares2-MVs can directly target tumor tissues in vivo, and 20 µg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

pH-regulated Tannic acid and soybean protein isolate adhesive for enhanced performance in plant-based meat analogues.

A food adhesive comprising tannic acid (TA) and soybean protein isolate (SPI) was developed to establish a cohesive bond between soy protein gel and simulated fat. The impact of varying TA concentrations and pH levels on the adhesive's rheology, thermal stability, chemical structure, and tensile strength were investigated. Rheological results revealed a gradual decrease in adhesive viscosity with increasing TA content. Differential scanning calorimetry (DSC) and thermal gravimetric (TG) results indicated that the stability of the adhesive improved with higher TA concentrations, reaching its peak at 0.50% TA addition. The incorporation of TA resulted in the cross-linking of amino group in unfolded SPI molecules, forming a mesh structure. However, under alkaline conditions (pH 9), adhesive viscosity and stability increased compared to the original pH. This shift was due to the disruption of the SPI colloidal charge structure, an increase in the stretching of functional groups, further unfolding of the structure, and an enhanced binding of SPI to TA. Under the initial pH conditions, SPI reacted with TA's active site to form covalent crosslinked networks and hydrogen bonds. In alkaline condition, beyond hydrogen and ionic bonding, the catechol structure was oxidized, forming an ortho-quinone that crosslinked SPI and created a denser structure. Tensile strength measurements and freeze-thaw experiments revealed that the adhesive exhibited maximum tensile strength and optimal adhesion with 0.75% TA at pH 9, providing the best overall performance. This study provides a new formulation and approach for developing plant-based meat analogues adhesives.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

Spontaneous delayed migration or shortening after pipeline embolization device treatment of intracranial aneurysm: incidence, management, and risk factors.

BACKGROUND: Studies reporting spontaneous delayed migration or shortening (SDMS) after treatment with the Pipeline Embolization Device (PED) are limited. This study aimed to evaluate the incidence of SDMS after PED treatment, propose management strategies, and identify the risk factors contributing to its occurrence. METHODS: We retrospectively reviewed consecutive patients with an intracranial aneurysm (IA) treated with PEDs at three institutions. SDMS was classified as type I or II based on whether the PED covered the aneurysm neck. RESULTS: The total cohort comprised 790 patients. SDMS was identified in 24 (3.04%) patients. Eighteen of the 24 patients had type I SDMS and did not require retreatment, while the remaining six patients had type II SDMS and all received retreatment. Multivariate logistic regression showed that the difference between the proximal and distal parent artery diameters (DPAD) (adjusted OR 2.977; 95% CI 1.054 to 8.405; P=0.039) and device tortuosity index (DTI) (adjusted OR 8.059; 95% CI 2.867 to 23.428; P<0.001) were independent predictors of SDMS after PED treatment, while the difference in length (DL) (adjusted OR 0.841; 95% CI 0.738 to 0.958; P=0.009) and PED plus coiling (adjusted OR 0.288; 95% CI 0.106 to 0.785; P=0.015) were protective factors. CONCLUSION: The incidence of SDMS after PED treatment of IA was 3.04%. For patients with type I SDMS with incomplete aneurysm occlusion we recommend continuous imaging follow-up while, for patients with type II SDMS, we recommend aggressive retreatment. The DPAD and DTI were independent risk predictors of SDMS after PED treatment, while the DL and PED plus coiling were protective factors.

Unveiling novel anti-viral mechanisms of ε-poly-l-lysine on tobacco mosaic virus-infected Nicotiana tabacum through microRNA and transcriptome sequencing.

MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.

CO2 sequestration in microbial electrolytic cell-anaerobic digestion system combined with mineral carbonation for sludge hydrolysate treatment.

The combination of microbial electrolytic cells and anaerobic digestion (MEC-AD) became an efficient method to improve CO2 capture for waste sludge treatment. By adding CaCl2 and wollastonite, the CO2 sequestration effect with mineral carbonation under 0 V and 0.8 V was studied. The results showed that applied voltage could increase dissolved chemical oxygen demand (SCOD) degradation efficiency and biogas yield effectively. In addition, wollastonite and CaCl2 exhibited different CO2 sequestration performances due to different Ca2+ release characteristics. Wollastonite appeared to have a better CO2 sequestration effect and provided a wide margin of pH change, but CaCl2 released Ca2+ directly and decreased the pH of the MEC-AD system. The results showed methane yield reached 137.31 and 163.50 mL/g SCOD degraded and CO2 content of biogas is only 12.40 % and 2.22 % under 0.8 V with CaCl2 and wollastonite addition, respectively. Finally, the contribution of chemical CO2 sequestration by mineral carbonation and biological CO2 sequestration by hydrogenotrophic methanogenesis was clarified with CaCl2 addition. The chemical and biological CO2 sequestration percentages were 46.79 % and 53.21 % under 0.8 V, respectively. With the increased applied voltage, the contribution of chemical CO2 sequestration rose accordingly. The findings in this study are of great significance for further comprehending the mechanism of calcium addition on CO2 sequestration in the MEC-AD system and providing guidance for the later engineering application.

Cadmium immobilization in soil using phosphate modified biochar derived from wheat straw.

The phosphate-modified biochar (BC) immobilizes cadmium (Cd), yet little is known about how phosphate species affect Cd detoxification in contaminated soils. We developed phosphate-modified biochar through the pyrolysis of wheat straw impregnated with three types of phosphate: mono­potassium phosphate (MKP), dipotassium hydrogen phosphate (DKP), and tripotassium phosphate (TKP). The Cd adsorption mechanism of modified biochar was investigated by biochar characterization, adsorption performance evaluation, and soil incubation tests. The results demonstrated that the efficiency of biochar in immobilizing Cd2+ followed the order: TKP-BC > DKP-BC > MKP-BC. The TKP-BC had the highest orthophosphate content, the fastest adsorption rate, and the largest adsorption capacity (Langmuir) of 257.28 mg/g, which is 6.31 times higher than that of the unmodified BC (CK). In contrast, pyrophosphate was predominant in MKP-BC and DKP-BC. The primary adsorption mechanism for Cd2+ was precipitation, followed by cation exchange, as evidenced by the formation of CdP minerals on the BC surface, and an increase of K+ in solution (compared to water-soluble K+) and a decrease of K+ in the biochar during adsorption. Desorption of Cd from the TKP-BC after adsorption was 9.77 %-12.39 % at a pH of 5-9, much lower than that of CK. The soil incubation test showed the diethylenetriaminepentaacetic acid extracted Cd of TKP-BC, MKP-BC, and DKP-BC was reduced by 67.93 %, 18.41 % and 31.30 % over CK, respectively. Using the planar optodes technique, we also found that TKP-BC had the longest effect enhancing in situ soil pH. This study provides a theoretical basis for developing heavy metal pollution control technology using green remediation materials and offers insights into the remediation mechanisms.

Comparation of the effectiveness of conventional needle irrigation and photon-induced photoacoustic streaming with sodium hypochorite in the treatment of teeth with apical periodontitis: a randomized clinical trial.

Photon-initiated photoacoustic streaming (PIPS) with an Er: YAG laser has been introduced in root canal treatment to improve irrigation and facilitate the removal of bacteria in the root canal system. This study aimed to compare the antibacterial effectiveness of two different root canal irrigation techniques, conventional needle irrigation (CNI) and PIPS, using 1% sodium hypochlorite (NaOCl), in the treatment of teeth with apical periodontitis. Sixty patients with a total of sixty teeth affected by apical periodontitis were included in this study. The teeth underwent root canal therapy, and after mechanical instrumentation, they were randomly assigned to two groups (n = 30) based on the final irrigation protocol: CNI or PIPS with 1% NaOCl. Bacterial suspensions in the root canals were evaluated using Adenosine 5'-triphosphate (ATP) assay kit after mechanical instrumentation and after final irrigation. Then, a follow-up was conducted after 7 days. The results revealed that final irrigation significantly reduced ATP values in both the CNI and PIPS groups (P < 0.001). The ATP values after final irrigation was greater in the CNI group compared to the PIPS group (P < 0.001). After a 7-day follow-up, percussion tenderness and fistula were significantly resolved in both groups (P < 0.05). A multivariate linear regression model was used to identify the factors that influence post irrigation ATP values. The analysis demonstrated that pre-operative percussion tenderness (P = 0.006), the presence of a fistula (P < 0.001) and the method used in the final irrigation (P < 0.001) had a significant impact on the ATP value after final irrigation. These results indicate that employing PIPS with 1% NaOCl as the final irrigation protocol exhibited superior antibacterial effectiveness and has the potential to enhance clinical outcomes in the treatment of teeth afflicted with apical periodontitis.

Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis.

BACKGROUND: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. METHODS: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. RESULTS: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1ß in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSIONS: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy.

Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences. Responders exhibit enhanced activity in the alternative/lectin complement pathway and higher levels of lysophosphatidylcholines (LysoPCs), predicting a favorable prognosis. Non-responders are enriched for immunoglobulins, predicting worse outcomes. Compared to normal controls, HCC plasma proteins show acute inflammatory response and platelet activation, while LysoPCs decrease. Combination therapy increases LysoPCs/phosphocholines in responders. Logistic regression/random forest models using metabolomic features achieve good performance in the prediction of responders. Proteomic analysis of cancer tissues unveils molecular features that are associated with side effects in responders receiving combination therapy. In conclusion, our analysis identifies plasma features associated with uHCC responders to combination therapy.

Octadecyl Gallate and Lipid-Modified MnSe2 Nanoparticles Enhance Radiosensitivity in Esophageal Squamous Cell Carcinoma and Promote Radioprotection in Normal Tissues.

Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe2 -lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate on surface of MnSe2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn2+ promotes radiosensitivity by generating reactive oxygen species induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells, and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy, and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment.

How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature.

PURPOSE: To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT). METHODS: From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively. RESULTS: The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm. CONCLUSIONS: JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

Akebia saponin D attenuates allergic airway inflammation through AMPK activation.

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 µΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents.

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients. This is attained by elaborate crosstalk between Notch and NF-κB pathways. Mechanistically, Notch receptors activated by HTNV enhance NF-κB signaling by recruiting IKKß and p65, promoting inflammatory macrophage polarization in both species. However, in mice rather than humans, Notch-mediated inflammation is timely restrained by a series of murine-specific long noncoding RNAs transcribed by the Notch pathway in a negative feedback manner. Among them, the lnc-ip65 detaches p65 from the Notch receptor and inhibits p65 phosphorylation, rewiring macrophages from the pro-inflammation to the pro-resolution phenotype. Genetic ablation of lnc-ip65 leads to destructive HTNV infection in mice. Thus, our findings reveal an immune-braking function of murine noncoding RNAs, offering a special therapeutic strategy for HTNV infection.

Preparations, application of polysaccharide-protein nanoparticles and their assembly at the oil-water interface.

With the development of nanotechnology, nanoparticles have played an important role in pharmaceuticals, foods and materials, in particular, protein/polysaccharide based composite nanoparticles have received attention from researchers for safety and green production. This paper summarized in detail the preparation methods, applications of protein/polysaccharide nanoparticles (PPNPs) in recent years, especially the mechanism of stabilizing the oil-water interface. Currently, the polysaccharides applied are more traditional, such as chitosan, pectin and carboxymethyl cellulose, so there is still a lot of room for the development of raw materials that can be used to prepare PPNPs. Based on this, we also proposed three promising polysaccharides: seaweed polysaccharide, lycium barbarum polysaccharide and lactobacillus exopolysaccharides, describing their characteristics as well as their application prospects, this article can serve as a reference for interested researchers.