Pre-Service Teachers' GenAI Anxiety, Technology Self-Efficacy, and TPACK: Their Structural Relations with Behavioral Intention to Design GenAI-Assisted Teaching.

Generative artificial intelligence (GenAI) has taken educational settings by storm in the past year due to its transformative ability to impact school education. It is crucial to investigate pre-service teachers' viewpoints to effectively incorporate GenAI tools into their instructional practices. Data gathered from 606 pre-service teachers were analyzed to explore the predictors of behavioral intention to design Gen AI-assisted teaching. Based on the Unified Theory of Acceptance and Use of Technology (UTAUT) model, this research integrates multiple variables such as Technological Pedagogical Content Knowledge (TPACK), GenAI anxiety, and technology self-efficacy. Our findings revealed that GenAI anxiety, social influence, and performance expectancy significantly predicted pre-service teachers' behavioral intention to design GenAI-assisted teaching. However, effort expectancy and facilitating conditions were not statistically associated with pre-service teachers' behavioral intentions. These findings offer significant insights into the intricate relationships between predictors that influence pre-service teachers' perspectives and intentions regarding GenAI technology.

Atomic layer deposited TiO2 nanofilm on titanium implant for reduced the release of particles.

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants. Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs. Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects. Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Ca2+ oscillation in vascular smooth muscle cells control myogenic spontaneous vasomotion and counteract post-ischemic no-reflow.

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we find myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential (ΔΨm) permanently impairs mitochondria-endoplasmic reticulum (ER) contacts and abolish Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restores cytosolic Ca2+ homeostasis, remotivates myogenic spontaneous vasomotion, achieves optimal reperfusion, and ameliorates neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.

Bacteriophage LHE83 targeting OmpA as a receptor exhibited synergism with spectinomycin against Escherichia coli.

Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.

Deformable registration of preoperative MR and intraoperative long-length tomosynthesis images for guidance of spine surgery via image synthesis.

PURPOSE: Improved integration and use of preoperative imaging during surgery hold significant potential for enhancing treatment planning and instrument guidance through surgical navigation. Despite its prevalent use in diagnostic settings, MR imaging is rarely used for navigation in spine surgery. This study aims to leverage MR imaging for intraoperative visualization of spine anatomy, particularly in cases where CT imaging is unavailable or when minimizing radiation exposure is essential, such as in pediatric surgery. METHODS: This work presents a method for deformable 3D-2D registration of preoperative MR images with a novel intraoperative long-length tomosynthesis imaging modality (viz., Long-Film [LF]). A conditional generative adversarial network is used to translate MR images to an intermediate bone image suitable for registration, followed by a model-based 3D-2D registration algorithm to deformably map the synthesized images to LF images. The algorithm's performance was evaluated on cadaveric specimens with implanted markers and controlled deformation, and in clinical images of patients undergoing spine surgery as part of a large-scale clinical study on LF imaging. RESULTS: The proposed method yielded a median 2D projection distance error of 2.0 mm (interquartile range [IQR]: 1.1-3.3 mm) and a 3D target registration error of 1.5 mm (IQR: 0.8-2.1 mm) in cadaver studies. Notably, the multi-scale approach exhibited significantly higher accuracy compared to rigid solutions and effectively managed the challenges posed by piecewise rigid spine deformation. The robustness and consistency of the method were evaluated on clinical images, yielding no outliers on vertebrae without surgical instrumentation and 3% outliers on vertebrae with instrumentation. CONCLUSIONS: This work constitutes the first reported approach for deformable MR to LF registration based on deep image synthesis. The proposed framework provides access to the preoperative annotations and planning information during surgery and enables surgical navigation within the context of MR images and/or dual-plane LF images.

Combined association of urinary volatile organic compounds with chronic bronchitis and emphysema among adults in NHANES 2011-2014: The mediating role of inflammation.

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weight quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Background: Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Methods: Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. Results: This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. Conclusions: This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Subtypes of Blastocystis in Tibetan Antelope (Pantholops hodgsonii).

Blastocystis is a protist that is distributed in the gut tract of humans and animals. However, the reports about Blastocystis infection in Tibetan antelope are scarce. We collected 173 Tibetan antelope feces samples from Xinjiang, Qinghai and Xizang, and amplified the SSU rRNA gene of 600 bp region of Blastocystis in our research. Fifty-one samples in total were positive for Blastocystis, with all subtypes being ST31. The lowest prevalence of Blastocystis was observed in Xizang (2/20, 9.1%), followed by Qinghai (18/92, 16.4%), Xinjiang (31/61, 33.7%). The highest prevalence of Blastocystis in Tibetan antelope was detected during the summer was (19/30, 38.8%). This is the first research work regarding the Blastocystis subtypes ST31 in Tibetan antelope. Our research provides information for future researches on the distribution of this Blastocystis subtype and the control of Blastocystis infection.

Existing hip joint disease is associated with an increased incidence of hip fracture in adults: A retrospective survey of 9710 individuals from a single center.

Objective: In hip disease patients, pain and movement restrictions might cause changes in bone strength and increase the likelihood of falls, finally leading to hip fracture. The aim of this study was to identify the incidence of, characteristics of and risk factors for hip fracture in patients with existing hip disease. Methods: This was a retrospective cohort study. Patients with existing hip disease treated at both outpatient and inpatient departments of our institute were identified by searching the electronic medical record system and followed retrospectively for the occurrence of hip fracture. Demographic and clinical characteristics, such as age, sex and kind of primary hip disease, were collected from the electronic medical record system. The incidence and timing of hip fracture were estimated, and a Cox regression model was built to identify the independent risk factors for hip fracture in these patients. Results: A total of 9710 eligible patients were included. After a mean follow-up of 3.97 years, hip fractures were identified in 95 patients, for an estimated incidence of hip fracture of 978.37 per 100,000 patients. The femoral neck was involved in 49 fractures (51.58 %), and the femoral trochanter was involved in 45 fractures (47.37 %). Four independent risk factors and one protective factor for hip fracture in patients with hip diseases were identified: age (HR = 1.116, 95 % CI = 1.094-1.138), the presence of osteonecrosis of the femoral head (HR = 2.201, 95 % CI = 1.217-3.980), a lower Harris hip score (HR = 0.966, 95 % CI = 0.949-0.982), a history of previous hip surgery (HR = 2.126, 95 % CI = 1.304-3.466) and the use of walking aids (HR = 0.588, 95 % CI = 0.354-0.975). A scoring system with a total score of 20 points was built, which included all of the above risk factors. The predictive scores for a low risk (estimated incidence of hip fracture ≤30 %), a moderate risk (estimated incidence of hip fracture 31 %-69 %), and a high risk (estimated incidence of hip fracture ≥70 %) of hip fracture were ≤8.5 points, 9.0-13.0 points and ≥13.5 points, respectively. Conclusion: The incidence of hip fracture in the special population of patients with existing hip disease was determined. Elderly patients, patients with a history of hip surgery, patients with osteonecrosis and patients with poor Harris hip scores were at increased risk of hip fracture. In patients with a predictive score greater than 9 points, indicating a moderate to high risk of hip fracture, the use of a walking aid might reduce the risk of hip fracture.

"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury.

Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.

Meta-analysis of the global prevalence and risk factors of Enterocytozoon bieneusi infection in pigs from 1999 to 2021.

Enterocytozoon bieneusi (E. bieneusi), which is one of the most common microsporidia, has been identified as an important obligate intracellular pathogen that commonly colonizes in a variety of animal species and humans worldwide, including humans. In this study, the statistical analyses of E. bieneusi infection and prevalence were performed to clarify the relationship between different genotypes in different countries. The databases Chinese National Knowledge Infrastructure (CNKI), VIP Chinese Journal Database, Wanfang Data, PubMed, Web of Science and ScienceDirect were used for data collection. The research data were subjected to subgroup, univariate regression, and correlation, to reveal factors related to the high prevalence of E. bieneusi. A total of, 34 of the 498 articles published before April 2022 met the inclusion criteria. The global prevalence of E. bieneusi in pigs was 37.69% (5175/12672). The prevalence of E. bieneusi in nursery pigs was 58.87% (588/946). In developing countries and Asia, the highest prevalence of E. bieneusi in pigs were 37.62% (4752/11645) and 40.14% (4715/11345), respectively. Moreover, humans and pigs have been found to be infected with the same genotype of E. bieneusi in some cases, as evidenced by the consolidation of genotype information. The results showed that pigs are susceptible to E. bieneusi during the nursery period. The prevalence of E. bieneusi is high in developing countries, and its genotype prevalence varies in each country. Thus, it is essential to strengthen the health inspection of vulnerable groups and customs quarantine inspection.

A Differential Protein Study on Bronchoalveolar Lavage Fluid at Different Stages of Silicosis.

OBJECTIVES: In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. METHODS: The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. RESULTS: Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages Ⅲ/control, stages Ⅱ/control, stage Ⅰ/control, stages Ⅲ/ stages Ⅱ, stages Ⅲ/ stage Ⅰ and stages Ⅱ/ stage Ⅰ groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. CONCLUSION: The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.

Transcriptomic profiling of long non-coding RNAs and messenger RNAs in the liver of mice during Toxoplasma gondii infection.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. METHODS: In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. RESULTS: By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. CONCLUSIONS: Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection.

Identification of potentially high drug-like VEGFR2/c-Met dual-target type II kinase inhibitors with symmetric skeletons based on structural screening.

Vascular endothelial growth factor receptor 2 (VEGFR2) and c-Mesenchymal epithelial transition factor (c-Met) are tyrosine kinase receptors associated with the occurrence of malignant tumors. Studies have shown that inhibition of VEGFR2 promotes a feedback increase in c-Met, a mechanism linked to the emergence of resistance to VEGFR2 inhibitors. Therefore, treatment targeting both VEGFR2 and c-Met will have better application prospects. In this study, hierarchical virtual screening was performed on ZINC15, Molport and Mcule-ULTIMATE databases to identify potential VEGFR2/c-Met dual inhibitors. Firstly, the best pharmacophore model for each target was used to cross-screen the three databases, and the compounds that could match the two pharmacophore models were then retained based on the Fit Value of the respective crystal ligands. Compounds ZINC, MOL, and MLB named after their database sources were retained by binding pattern analysis and docking assessment. ADMET predictions indicated that ZINC had significantly higher oral bioavailability compared to the approved drug cabozantinib. This is likely due to ZINC's unique symmetrical backbone with less structure complexity, which may reduce the occurrence of adverse effects. Molecular dynamics simulations and binding free energy analysis showed that all three hit compounds were able to stably bind at the active site, but only ZINC could form high occupancy of hydrogen bonds with both VEGFR2 and c-Met, and also only ZINC had a higher binding free energy than crystal ligands, suggesting that ZINC was the most likely potential VEGFR2/c-Met dual-target inhibitor. This finding provides a promising starting point for the development of VEGFR2/c-Met dual-target inhibitors.Communicated by Ramaswamy H. Sarma.

Double-edged effect of frequent freeze-thaw on the stability of zero-valent iron after heavy metal remediation.

Freeze-thaw cycles (FTCs) cause dynamic microscale changes in ions and solvents. During freezing, heavy metals adsorbed on zero-valent iron (M-ZVI) and protons are excluded by ice crystals and concentrated in the liquid-like grain boundary region. The high proton concentration in this region leads to the dissolution of the passivation layer of ZVI. To assess the environmental risks of M-ZVI during FTCs, this study evaluated the stability of M-ZVI in this scenario from both microscale and macroscale perspectives. The results showed that the dissolution of the passivation layer had a dual effect on the stability of M-ZVI, which depends on the by-products of M-ZVI. The dissolution of the passivation layer was accompanied by the leaching of heavy metals, such as Ni-ZVI, but it also enhanced the reactivity of ZVI, causing it to re-react with desorbed heavy metals. The stability of Cr-ZVI and Cd-ZVI was improved due to frequent FTCs. Furthermore, changes in the surrounding environment (water dipole moment, ion concentration, etc.) of ZVI affected the crystallization of Fe oxides, increasing the content of amorphous Fe oxide. As low-crystallinity Fe oxides could facilitate ion doping, Ni2+ was doped into Fe3O4 lattice during FTCs, which reduced the mobility of heavy metals. Contrary to traditional views that freezing temperatures slow chemical reactions, this study provides new insights into the application of iron-based materials in cold environments.

Echinacoside Prevents Sepsis-Induced Myocardial Damage via Targeting SOD2.

Echinacoside (ECH) is a prominent naturally occurring bioactive compound with effects of alleviating myocardial damage. We aimed to explore the beneficial effects of ECH against sepsis-induced myocardial damage and elucidate the potential mechanism. Echocardiography and Masson staining demonstrated that ECH alleviates cardiac function and fibrosis in the cecal ligation and puncture (CLP) model. Transcriptome profiling and network pharmacology analysis showed that there are 51 overlapping targets between sepsis-induced myocardial damage and ECH. Subsequently, chemical carcinogenesis-reactive oxygen species (ROS) were enriched in multiple targets. Wherein, SOD2 may be the potential target of ECH on sepsis-induced myocardial damage. Polymerase chain reaction results showed that ECH administration could markedly increase the expression of SOD2 and reduce the release of ROS. Combined with injecting the inhibitor of SOD2, the beneficial effect of ECH on mortality, cardiac function, and fibrosis was eliminated, and release of ROS was increased after inhibiting SOD2. ECH significantly alleviated myocardial damage in septic mice, and the therapeutic mechanism of ECH is achieved by upregulating SOD2 which decreased the release of ROS.

CXCR4-Expressing Mesenchymal Stem Cells Derived Nanovesicles for Rheumatoid Arthritis Treatment.

Cell membrane camouflage technology, which a demonstrated value for the bionic replication of natural cell membrane properties, is an active area of ongoing research readily applicable to nanomedicine. How to realize immune evasion, slow down the clearance from the body, and improve targeting are still worth great efforts for this technology. Herein, novel cell membrane-mimicked nanovesicles from genetically engineered mesenchymal stem cells (MSCs) are presented as a potential anti-inflammatory platform for rheumatoid arthritis (RA) management. Utilizing the synthetic biology approach, the biomimetic nanoparticles are constructed by fusing C-X-C motif chemokine receptor4 (CXCR4)-anchored MSC membranes onto drug-loaded polymeric cores (MCPNs), which make them ideal decoys of stromal cell-derived factor-1 (SDF-1)-targeted arthritis. These resulting nanocomplexes function to escape from the immune system and enhance accumulation in the established inflamed joints via the CXCR4/SDF-1 chemotactic signal axis, thereby achieving an affinity to activated macrophages and synovial fibroblasts. It is further demonstrated that the MCPNs can significantly suppress synovial inflammation and relieve pathological conditions with favorable safety properties in collagen-induced arthritis mice. These findings indicate the clinical value of MCPNs as biomimetic nanodrugs for RA therapy and related diseases.