Examining drivers of NFT purchase intention: The impact of perceived scarcity and risk.

The emergence of non-fungible tokens (NFTs) has elicited both excitement and apprehension among consumers, who find themselves influenced by the perceived scarcity and the perceived risks surrounding these novel digital assets. This study investigates the factors influencing consumer adoption of NFTs by integrating the concepts of perceived scarcity and perceived risks within the theoretical framework of the Theory of Planned Behavior (TPB). Employing structural equation modeling, the research evaluates the impact of perceived scarcity, perceived ease of use, attitudes, subjective norms, perceived behavioral control, and perceived risk on NFT purchase intentions. The findings reveal that perceived scarcity and perceived ease of use significantly positively affect consumers' intentions to purchase NFTs. Conversely, perceived risk exerts a negative effect on purchase intentions. Additionally, the study demonstrates that attitudes, subjective norms, and perceived behavioral control positively affect NFT purchase intentions. This study provides a behavioral roadmap for navigating the complex love-hate relationship consumers have with NFTs, shedding light on the factors that motivate individuals to embrace or avoid these digital collectibles.

Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells. METHODS: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 µM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects. RESULTS: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others. CONCLUSION: Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.

Continuous Positive Airway Pressure Treatment and Hypertensive Adverse Outcomes in Pregnancy: A Systematic Review and Meta-Analysis.

Importance: Pregnancy may contribute to the development or exacerbation of obstructive sleep apnea (OSA) and increase the risk of gestational complications. Continuous positive airway pressure (CPAP) is the first-line and criterion standard treatment for OSA and is regarded as the most feasible choice during pregnancy. However, the association between CPAP therapy in pregnant women with OSA and reduced gestational complications remains inconclusive. Objective: To investigate the association between CPAP therapy in pregnant women with OSA and the reduction of adverse hypertensive outcomes during gestation. Data Sources: Keyword searches of PubMed, Embase, and the Cochrane Database of Systematic Reviews and Clinical Trials were conducted from inception to November 5, 2023. Study Selection: Original studies reporting the treatment effect of CPAP use on lowering hypertension and preeclampsia risks in pregnant women with OSA were selected. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed in the reporting of reviews. Data were independently extracted by 2 authors. Random-effects model meta-analyses were performed and risk ratios (RRs) reported. Subgroup analysis, meta-regression based on age and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and publication bias assessment were also conducted. Main Outcome and Measures: The primary outcome was the RR of gestational hypertension and preeclampsia between pregnant women with OSA receiving CPAP treatment and those who did not receive CPAP treatment. Results: Six original studies in 809 participants (mean age, 31.4 years; mean BMI, 34.0) were identified and systematically reviewed for meta-analysis. The pooled results showed significant differences between the intervention (CPAP use) and the control (non-CPAP use) groups in reducing the risk of gestational hypertension (RR, 0.65; 95% CI, 0.47-0.89; P = .008) and preeclampsia (RR, 0.70; 95% CI, 0.50-0.98; P = .04). Meta-regression revealed that patients' age (coefficient, -0.0190; P = .83) and BMI (coefficient, -0.0042; P = .87) were not correlated with reduction of risk of hypertension and preeclampsia. Conclusions and Relevance: These findings suggest that implementing CPAP treatment in pregnant women with OSA may reduce the risk of gestational hypertension and preeclampsia.

A case report of high cervical spinal infarction after stenting with severe stenosis at the beginning of left vertebral artery.

BACKGROUND: Spinal cord infarction is an uncommon nervous system disorder. We present a case of high cervical cord infarction caused by stenting of the origin of the left vertebral artery (VA). The incidence of spinal cord infarction is minimal, and it must be distinguished from a number of other disorders. The diagnosis is primarily based on imaging, clinical symptoms, and history. Currently, there is no focused treatment for spinal cord infarction. Thrombolysis, high-dose glucocorticoid shocks, tube dilatation to promote circulation, and nutritional neurotropic medicines given early in the course of the disease can all help to slow the disease's progression. There is no agreement on the etiology, diagnosis, or therapy options for these people. CASE PRESENTATION: On October 7, 2023, an 81-year-old man was admitted to the hospital primarily for recurrent chest tightness and pain that had persisted for more than 2 years and 1 month. Cerebral angiography upon admission revealed significant blockage of the right VA and stenosis of the left vertebral arterial origin. Six days following admission, a drug-eluting stenting procedure was carried out under local anesthesia to open the left VA origin via the femoral artery. Following the procedure, the patient experienced a progressive loss of muscle strength in all 4 limbs and paraplegia below the cervical 3 spinal cord. One week following the procedure, the patient was released from the hospital. After the procedure, the patient was released 1 week later. After the procedure, the patient's symptoms persisted for a month. CONCLUSION: High awareness for high cervical cord infarction is required when neck discomfort and limb weakness with progressive progression arises after surgery. Complications of high cervical cord infarction following stenting for stenosis of VA origin are uncommon in clinical settings. Patients' prognoses can be improved by prompt diagnosis and care.

Multi-omics and pharmacological characterization of patient-derived glioma cell lines.

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.

Facilitating and hindering factors of community nurses' emergency and critical care treatment abilities: A qualitative study.

BACKGROUND: This study adopts a descriptive phenomenological approach to investigate the facilitators and barriers of community nurses' abilities in managing critical and emergency conditions. With the transition of healthcare systems to the community, the evolution of nursing practices, and the attention from policies and practices, community nurses play a crucial role in the management of critical and emergency conditions. However, there is still a lack of comprehensive understanding regarding the factors that promote or hinder their capabilities in this area. AIM: To understand the facilitators and barriers of community nurses in managing critical and emergency conditions, exploring the fundamental reasons and driving forces influencing their treatment capabilities. METHODS: This study utilized the destination sampling method between May 2023 and July 2023. It employed a descriptive phenomenological approach within qualitative research methodologies. Through objective sampling, 17 community nurses from 7 communities in Changning District, Shanghai, were selected as the study subjects. Semi-structured interviews were conducted to gather data, which were subsequently organized and analyzed using Colaizzi's seven-step analysis method, leading to the extraction of final themes. RESULTS: The barrier factors identified from the interviews encompassed three topics: resource allocation, professional factors, and personal literacy. The facilitators comprised three themes: professionalism, management attention, and training and continuing education. We identified that the root causes of the barriers included the lack of practical treatment experience among community nurses, insufficient awareness of self-directed learning, and limited knowledge and technical proficiency. The professional quality of community nurses and management attention serve as motivation for them to enhance their treatment abilities. CONCLUSION: To enhance the capability of community nurses in treating acute and critical patients, it is recommended to bolster training specifically tailored to acute and critical care, raise awareness of first aid practices, and elevate knowledge and skill levels.

A 3D bioreactor model to study osteocyte differentiation and mechanobiology under perfusion and compressive mechanical loading.

Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (ß-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5 % strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network. STATEMENT OF SIGNIFICANCE: This study highlights the importance of creating a three-dimensional (3D) in vitro model to study osteocyte differentiation and mechanobiology, as cellular functions are limited in two-dimensional (2D) models lacking in vivo tissue organization. By using a perfusion bioreactor platform, physiological conditions of fluid flow and compressive loading were mimicked to which osteocytes are exposed in vivo. Microporous poly(L-lactide-co-trimethylene carbonate) lactide (LTMC) scaffolds in 3D are identified as a valuable tool to create a favorable environment for osteocyte differentiation and to enable mechanical stimulation of osteocytes by perfusion and compressive loading. The LTMC platform imitates the mechanical bone environment of osteocytes, allowing the analysis of the interaction with other cell types in bone under in vivo biophysical stimuli.

Comparison of Budesonide/formoterol versus Fluticasone furoate/vilanterol as maintenance and reliever therapy for asthma control: a real-world observational study.

BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Inhibiting interferon-γ induced cancer intrinsic TNFRSF14 elevation restrains the malignant progression of glioblastoma.

BACKGROUND: Prolonged interferon-γ signaling activation induces cancer resistance to therapeutics, especially immunotherapy. However, the detailed mechanisms are not well characterized. In present study, we explored cancer intrinsic resistant mechanisms employing for evading immune checkpoint blockade (ICB) and searched for key immune checkpoints contributing to the constitution of suppressive immune microenvironment of glioblastoma (GBM). METHODS: We screened key immune checkpoint (IC) associated with IFN signaling activation in GBM according to integrated transcriptomic profiling on the ICs. Expression analysis and functional assays revealed that malignant cells elevated the key IC, TNFRSF14 expression under IFN-γ stimulation, which enhanced their proliferation and in vivo tumorigenicity. Therapeutic efficiency of TNFRSF14 disruption in GBM was evaluated with in vitro and in vivo functional assays, including immunofluorescence, transwell, RT-qPCR, flow cytometry, mass cytometry, and mice preclinical GBM models. Moreover, the improvement of TNFRSF14 blockade on the efficacy of PD-L1 treatment was examined in mice intracranial xenograft bearing models. RESULTS: TNFRSF14, a previously poorly characterized IC, was disclosed as a checkpoint with malignant intrinsic elevation closely associated with type II not type I IFN signaling activation in GBM. Anti-PD-L1 treatment induces compensatory TNFRSF14 elevation, while enhancing IFN-γ production. TNFRSF14 phosphorylates FAK at Y397 and consequently activates NF-κB, which not only strengthens the tumorigenicity of GBM cells, but also enhances TAMs recruitment through elevating CXCL1/CXCL5 secretion from GBM cells. TNFRSF14 ablation reduces the tumorigenicity of GBM cells, reshapes the immunosuppressive microenvironment, and enhances therapeutic efficacy of anti-PD-L1 in mouse orthotopic GBM model. CONCLUSION: Our findings highlight a malignant TNFRSF14/FAK axis as a potential target to blunt cancer-intrinsic resistance to ICB treatment, which may help improve the therapeutic efficiency of immunotherapy in malignancies.

Impact of proximity of left atrium to descending aorta on left inferior pulmonary vein triggers or drivers of atrial fibrillation: A risk score model.

BACKGROUND: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers. OBJECTIVE: We aimed to assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures. METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from preablation pulmonary vein computed tomography. Patients were assigned to groups on the basis of the presence of LIPV triggers or drivers. Multivariate logistic regression was used to identify risk factors. RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers or drivers. The Dao-LIPV distance had a better predictive performance (area under the curve, 0.70) compared with persistent AF (area under the curve, 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤2.5 mm (odds ratio, 3.96; 95% CI, 2.15-7.29; P < .001) and persistent AF (odds ratio, 1.73; 95% CI, 1.02-2.94]; P = .044) were independent predictors for the presence of LIPV triggers or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤2.5 mm (11.4%), and both (15.0%). CONCLUSION: The proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤2.5 mm significantly increase the risk of LIPV triggers or drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.

5,7,3',4'-Tetramethoxyflavone suppresses TGF-ß1-induced activation of murine fibroblasts in vitro and ameliorates bleomycin-induced pulmonary fibrosis in mice.

OBJECTIVE: This study aimed to investigate the use of 5,7,3',4'-tetramethoxyflavone (TMF) to treat pulmonary fibrosis (PF), a chronic and fatal lung disease. In vitro and in vivo models were used to examine the impact of TMF on PF. METHODS: NIH-3T3 (Mouse Embryonic Fibroblast) were exposed to transforming growth factor­ß1 (TGF-ß1) and treated with or without TMF. Cell growth was assessed using the MTT method, and cell migration was evaluated with the scratch wound assay. Protein and messenger ribonucleic acid (mRNA) levels of extracellular matrix (ECM) genes were analyzed by western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Downstream molecules affected by TGF-ß1 were examined by western blotting. In vivo, mice with bleomycin-induced PF were treated with TMF, and lung tissues were analyzed with staining techniques. RESULTS: The in vitro results showed that TMF had no significant impact on cell growth or migration. However, it effectively inhibited myofibroblast activation and ECM production induced by TGF-ß1 in NIH-3T3 cells. This inhibition was achieved by suppressing various signaling pathways, including Smad, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/AKT (PI3K/AKT), and WNT/ß-catenin. The in vivo experiments demonstrated the therapeutic potential of TMF in reducing PF induced by bleomycin in mice, and there was no significant liver or kidney toxicity observed. CONCLUSION: These findings suggest that TMF has the potential to effectively inhibit myofibroblast activation and could be a promising treatment for PF. TMF achieves this inhibitory effect by targeting TGF-ß1/Smad and non-Smad pathways.

The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

Safety and efficacy of a modified endoscopic full-thickness resection technique for gastric submucosal tumors: a case series.

Objectives: Endoscopic full-thickness resection (EFTR) has proven effective and economical for patients with gastric submucosal tumors (SMTs). However, the poor operative field of view, the risk of massive hemorrhage, and the difficulties in defect closure have limited its widespread application. Herein, we described a modified EFTR technique developed to simplify the dissection and defect closure procedures using common and economical endoscopic accessories. Methods: Forty-two patients who underwent the modified EFTR for gastric SMTs in the Shenzhen Guangming District People's Hospital were enrolled in the case series. Following a cross incision to expose the intraluminal surface the tumors were captured by suction through a transparent cap and the roots were ligated using a loop. The tumors and part of the suction tissue were removed along the ligated root. A tension-relieving closure was performed by clipping the raised plica in four quadrants outside the ligated root. Patient demographics, tumor characteristics, and therapeutic outcomes were evaluated retrospectively. Results: All tumors had an R0 resection. The median procedure time was 51.8 min (IQR 34.25 min). No severe perioperative adverse events occurred. No residual lesion or recurrence was reported during the follow-up period of 9.84 months (IQR 5.0 months). Conclusion: The safety and practicability of Modified-EFTR could allow for wide clinical application in patients with micro-gastric SMTs.

Assessment of the Biocompatibility Ability and Differentiation Capacity of Mesenchymal Stem Cells on Biopolymer/Gold Nanocomposites.

This study assessed the biocompatibility of two types of nanogold composites: fibronectin-gold (FN-Au) and collagen-gold (Col-Au). It consisted of three main parts: surface characterization, in vitro biocompatibility assessments, and animal models. To determine the structural and functional differences between the materials used in this study, atomic force microscopy, Fourier-transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to investigate their surface topography and functional groups. The F-actin staining, proliferation, migration, reactive oxygen species generation, platelet activation, and monocyte activation of mesenchymal stem cells (MSCs) cultured on the FN-Au and Col-Au nanocomposites were investigated to determine their biological and cellular behaviors. Additionally, animal biocompatibility experiments measured capsule formation and collagen deposition in female Sprague-Dawley rats. The results showed that MSCs responded better on the FN-Au and Col-AU nanocomposites than on the control (tissue culture polystyrene) or pure substances, attributed to their incorporation of an optimal Au concentration (12.2 ppm), which induced significant surface morphological changes, nano topography cues, and better biocompatibility. Moreover, neuronal, endothelial, bone, and adipose tissues demonstrated better differentiation ability on the FN-Au and Col-Au nanocomposites. Nanocomposites have a crucial role in tissue engineering and even vascular grafts. Finally, MSCs were demonstrated to effectively enhance the stability of the endothelial structure, indicating that they can be applied as promising alternatives to clinics in the future.

Exploring the Anti-Inflammatory Effect of Tryptanthrin by Regulating TLR4/MyD88/ROS/NF-κB, JAK/STAT3, and Keap1/Nrf2 Signaling Pathways.

Tryptanthrin (TRYP) is the main active ingredient in Indigo Naturalis. Studies have shown that TRYP had excellent anti-inflammatory activity, but its specific mechanism has been unclear. In this work, the differentially expressed proteins resulting from TRYP intervention in LPS-stimulated RAW264.7 cells were obtained based on tandem mass tag proteomics technology. The anti-inflammatory mechanism of TRYP was further validated by a combination of experiments using the LPS-induced RAW264.7 cell model in vitro and the DSS-induced UC mouse model (free drinking 2.5% DSS) in vivo. The results demonstrated that TRYP could inhibit levels of NO, IL-6, and TNF-α in LPS-induced RAW264.7 cells. Twelve differential proteins were screened out. And the results indicated that TRYP could inhibit upregulated levels of gp91phox, p22phox, FcεRIγ, IKKα/ß, and p-IκBα and reduce ROS levels in vitro. Besides, after TRYP treatment, the health conditions of colitis mice were all improved. Furthermore, TRYP inhibited the activation of JAK/STAT3, nuclear translocation of NF-κB p65, and promoted the nuclear expression of Nrf2 in vitro and in vivo. This work preliminarily indicated that TRYP might suppress the TLR4/MyD88/ROS/NF-κB and JAK/STAT3 signaling pathways to exert anti-inflammatory effects. Additionally, TRYP could achieve antioxidant effects by regulating the Keap1/Nrf2 signaling pathway.

Carbon Dot Nanozyme Ameliorating Ischemia-Reperfusion-Induced Muscle Injury by Antioxidation and Downregulating iNOS/COX-2 Pathway.

Skeletal muscle ischemia-reperfusion (IR) injury is a prevalent type of muscle injury caused by events, such as trauma, arterial embolism, and primary thrombosis. The development of an IR injury is associated with oxidative stress and an excessive inflammatory response. Nanozymes, which have exceptional free radical scavenging activities, have gained significant attention for treating oxidative stress. This study demonstrates that carbon dot (C-dot) nanozymes possess superoxide dismutase (SOD)-like activity and can act as free radical scavengers. The carbon dot nanozymes are presented to mitigate inflammation by downregulating the iNOS/COX-2 pathway and scavenging reactive oxygen-nitrogen species to reduce oxidative stress, thereby suppressing inflammation. In the IR injury of skeletal muscle mice, we demonstrate that C-dots can effectively reduce inflammatory cytokines and tissue edema in skeletal muscle following IR injury in the limb. These findings suggest that C-dots have potential as a therapeutic approach for IR injury of skeletal muscle with negligible systemic toxicity. This offers a promising strategy for clinical intervention.

Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.

Introduction: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Methods: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. Results: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Discussion: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.

Nano-hydroxyapatite-assisted enzyme-induced carbonate precipitation enhances Pb-contaminated aqueous solution and loess remediation.

Intensive agricultural activities could cause lead (Pb) bioaccumulation, threatening human health. Although the enzyme-induced carbonate precipitation (EICP) technology has been applied to tackle the aforesaid problem, the urease may denature or even lose its activity when subjected to a significant Pb2+ toxicity effect. To this end, the nano-hydroxyapatite (nHAP)-assisted EICP was proposed to reduce the mobility of Pb2+. Results indicated that a below 30% immobilization efficiency at 60 mM Pb2+ was attained under EICP. nHAP adsorbed the majority of Pb2+, preventing Pb2+ attachment to urease. Further, hydroxylphosphohedyphane or hydroxylpyromorphite was formed at 60 mM Pb2+, followed by the formation of cerussite, allowing hydroxylphosphohedyphane or hydroxylpyromorphite to be wrapped by cerussite. By contrast, carbonate-bearing hydroxylpyromorphite of higher stability (Pb10(PO4)6CO3) was developed at 20 mM Pb2+ as CO3 2- substituted the hydroxyl group in hydroxylpyromorphite. Moreover, nHAP helped EICP to form nucleated minerals. As a result, the EICP-nHAP technology raised the immobilization efficiency at 60 mM Pb2+ up to 70%. The findings highlight the potential of applying the EICP-nHAP technology to Pb-containing water bodies remediation.