Biomimetic Copper-Doped Polypyrrole Nanoparticles For Enhanced Cancer Low-Temperature Photothermal therapy

INTRODUCTION: Photothermal therapy (PTT) has a significant potential for its application in precision tumour therapy. However, PTT-induced hyperthermia may damage healthy tissues and trigger the expression of heat shock proteins (HSPs), thereby compromising the long-term therapeutic efficacy of PTT. METHODS: In this study, a biomimetic drug delivery system comprising CuP nanozymes as the inner core and platelet membrane (PM) as the outer shell was successfully developed for administering synergistic chemodynamic therapy and mild PTT. PM is encapsulated on CuP to form this biomimetic nanoparticle (PM-coated CuP nanoparticles, PC). PC possesses peroxidase (POD) activity, can facilitate the conversion of hydrogen peroxide into ·OH, thereby inhibiting the expression of HSPs. RESULTS: Upon exposure to low-power laser irradiation (0.5 W/cm DISCUSSION: PC exhibits high efficacy and biocompatibility, making it a promising candidate for future applications

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients.Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell’s concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape.Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients.Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses

The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review

BackgroundGut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.MethodsThe gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).ResultsGut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88–97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn’s disease but low to very low quality for other diseases.ConclusionGut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT

Research on Credit Risk Measurement of Small and Micro Enterprises Based on the Integrated Algorithm of Improved GSO and ELM

Small and micro enterprises play a very important role in economic growth, technological innovation, employment and social stability etc. Due to the lack of credible financial statements and reliable business records of small and micro enterprises, they are facing financing difficulties, which has become an important factor hindering the development of small and micro enterprises. Therefore, a credit risk measurement model based on the integrated algorithm of improved GSO (Glowworm Swarm Optimization) and ELM (Extreme Learning Machine) is proposed in this paper. First of all, according to the growth and development characteristics of small and micro enterprises in the big data environment, the formation mechanism of credit risk of small and micro enterprises is analyzed from the perspective of granularity scaling, cross-border association and global view driven by big data, and the index system of credit comprehensive measurement is established by summarizing and analyzing the factors that affect the credit evaluation index. Secondly, a new algorithm based on the parallel integration of the good point set adaptive glowworm swarm optimization algorithm and the Extreme learning machine is built. Finally, the integrated algorithm based on improved GSO and ELM is applied to the credit risk measurement modeling of small and micro enterprises, and some sample data of small and micro enterprises in China are collected, and simulation experiments are carried out with the help of MATLAB software tools. The experimental results show that the model is effective, feasible, and accurate. The research results of this paper provide a reference for solving the credit risk measurement problem of small and micro enterprises and also lay a solid foundation for the theoretical research of credit risk management

Investigation of Water Impacts on Surface Properties and Performance of Air-Electrode in Reversible Protonic Ceramic Cells

Water, being abundant and readily accessible, gains widespread usage as proton source in many catalysis and energy conversion technologies, including applications like reversible protonic ceramic cells (R-PCCs). Revealing the influence of water on the electrode surface and reaction kinetics is critical for further improving their electrochemical performance. Herein, a hydrophilic air-electrode PrBa0.875Cs0.125Co2O5+δ is developed for R-PCC, which demonstrates a remarkable peak power density of 1058 mW cm-2 in fuel cell mode and a current density of 1354 mA cm-2 under 1.3 V in electrolyzing steam at 650 °C. For the first time on R-PCC, surface protons' behavior in response to external voltages is captured using in situ FTIR characterizations. Further, it is shown that contrary to the bulk proton uptake process that is thought to follow hydrogenation reactions and lead to cation reductions. The air-electrode presents enriched surface protons occurring through oxidizing surface cations, as confirmed by depth-profiling XPS results. H/D isotope exchange experiments and subsequent electrochemical characterization analyses reveal that the presence of protons enhances surface reactions. This study fills the knowledge gap between water-containing atmospheres and electrochemical performance by providing insights into the surface properties of the material. These new findings provide guidance for future electrode design and optimization

Effects of Nonpharmacological Interventions on Balance Function in Patients with Osteoporosis or Osteopenia: A Network Meta-Analysis of Randomized Controlled Trials

Objective. To evaluate the clinical efficacy of nonpharmacological interventions in improving balance function of patients with osteoporosis or osteopenia using network meta-analysis (NMA). Methods. We searched seven databases (PubMed, the Cochrane Library, Embase, CKNI, Wanfang Data, VIP, and CBM) for relevant randomized controlled trials (RCTs) up to August 31, 2020. Berg Balance Scale (BBS) and Time Up and Go Test (TUGT) were used as outcome measures. Two researchers independently screened studies, collected data from the studies, and estimated risk of study bias. Divergence in the evaluation process was settled by consulting a third researcher. We used Stata 15.1 software for network meta-analysis (NMA). Results. We identified 10 eligible RCTs, with a total of 737 patients and four intervention methods, including traditional Chinese medicine (TCM) exercises, pulsed electromagnetic fields (PEMFs), strength training, and balance and strength training. The results revealed that all nonpharmacological interventions could improve balance function, but the effect of balance and strength training was better than other interventions. Conclusion. Exercise can significantly improve the balance function of patients with osteoporosis and osteopenia, and balance combined with strength training has the best effect, followed by TCM exercises

Patient-Derived Microvesicles/AIE Luminogen Hybrid System for Personalized Sonodynamic Cancer Therapy in Patient-Derived Xenograft Models

Sonodynamic therapy (SDT), as an efficient way of tumor treatment, has the advantages of deep tumor penetration and high therapeutic efficacy. However, developing efficient sonosensitizers are still challenging. AIEgen-based SDT has never been reported and it is urgent to develop novel AIEgen-active sonosensitizers. Furthermore, the AIEgen-based theranostic system is promisingly needed to be proved on PDX models to be closer to the clinic. Herein, we constructed the first AIEgen based SDT system and found that DCPy has advantages over traditional sonosensitizers in SDT. Then, a patient-derived MVs/AIEgen hybrid system prepared by electroporation was used for personalized SDT in bladder cancer patient-derived xenograft (PDX) models. Impressively, AMVs displayed the superior tumor targeting ability and efficient personalized SDT therapy on PDX models, both of which were much more improved compared with PLGA/AIEgens nanoparticles and cell line-derived micro vesicles. This work presented the first example of an AIEgen-based hybrid system as sonosensitizer for SDT and provides new ideas for both the design of AIE-active sonosensitizers and the SDT treatment of cancers, further expanding the potential clinical application of AIEgens in the future.</p

Dynamic computed tomography manifestations of simulated wooden foreign bodies in blood-saline mixtures with variable concentrations and retention times

Abstract Diagnosing wooden foreign bodies (WFBs) using computed tomography (CT) is often missed, leading to adverse outcomes. This study aims to reduce misdiagnoses by exploring the density variation of blood-saline mixtures in ex vivo models. Twenty Cunninghamia lanceolata sticks, selected as WFB models, were randomly assigned to five groups: a control group (saline) and four experimental groups immersed in blood-saline mixtures with varying concentrations. The samples were then placed in a constant-temperature water bath at 36.8 °C. CT scans were performed in the lowest and highest density areas, and the volume of the low-density areas was measured at the post-processing workstation. Finally, the effects of time and concentration on imaging were analyzed, and fitting curves were generated. The blood-saline mixture concentration and time significantly affected the CT number in the three areas. WFB images changed dynamically over time, with two typical imaging signs: the bull's-eye sign on the short axis images and the tram line sign on the long axis images. Fitting curves of the CT number in the lowest density areas with different concentrations can quantify imaging changes. The CT number of the lowest density areas increased with time, following a logarithmic function type, while the CT number of the highest density areas exhibited a fast-rising platform type. The volume of the low-density areas decreased over time. The time of damage caused by WFBs and the influence of varying blood and tissue fluid contents at the damaged site should be considered in the diagnosis. Imaging changes from multiple CT scans at different times can aid in diagnosis

Changes of heavy metal in fresh and litter leaves of Neolamarckia cadamba and Schefflera arboricola under sewage sludge application

This study conducted a large root box experiment with Schefflera arboricola monoculture, Neolamarckia cadamba monoculture, and co-planting of Schefflera arboricola and Neolamarckia cadamba. The dynamic changes in Cu, Zn, Cd, and Hg contents in fresh and litter leaves of Schefflera arboricola and Neolamarckia cadamba and their litter leaves yield were analyzed for three months (September, October, and November 2020) after the surface application of 2% (W/W) sewage sludge (SS). The relationship between the heavy metal contents of fresh and litter leaves and the changes in the heavy metal return amount in litter leaves were further analyzed. The results were as follows: (1) N. cadamba had significantly higher Cu contents in fresh and litter leaves than those of S. arboricola, while had significantly lower Zn and Cd contents than those of S. arboricola. (2) The fresh leaves of S. arboricola had the lowest Zn content and the highest Hg content in November. (3) The fresh leaves of monoculture and co-planting Neolamarckia cadamba had the highest Zn, Cd, and Hg contents in November. (4) The Hg content in the litter leaves of co-planting of N. cadamba increased significantly with the time of SS application, while those of Cu, Zn, and Cd contents showed no significance. (5) The Cd content in fresh leaves was significantly and positively correlated with the Hg and Cd contents of litter leaves in Schefflera arboricola in both September and November. (6) The highest yield of litter leaves and the highest return amount of Cu, Zn, Cd, and Hg in S. arboricola occurred one month after SS application (September), while those in Neolamarckia cadamba occurred two months after SS application (October). In summary, the application time of SS showed a greater effect on the heavy metal contents in fresh leaves of N. cadamba and Schefflera arboricola than those in litter leaves; there was a positive correlation between the Cd content in the fresh leaves and the Cd and Hg contents in the litter leaves of S. arboricola; the heavy metal pollution risk of the litter leaves of S. arboricola and Neolamarckia cadamba was easy to occur in one month (September) and two months (October) after SS application, respectively. This study provides a reference for safe SS utilization and reasonable litter disposal in the landscape

Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus.

WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions, indicating tandem duplicate WRKYs in the adaptive responses to environmental stimuli during the evolution process. Our results provide a framework for future studies regarding the function of WRKY genes in response to stress in B. napus