Superior Efficacy Research Articles

Evaluating the diagnostic value of 18F-FAPI-04 PET/CT in various malignant tumors: a head-to-head comparison with 18F-FDG PET/CT.

This study aims to evaluate the diagnostic efficacy of 18F-fibroblast activation protein inhibitor-04 (18F-FAPI-04) PET/CT for various malignant tumors and compare it head-to-head with 18F-FDG PET/CT. This single-center, prospective study continuously recruited patients with suspected or confirmed malignant tumors for concurrent 18F-FDG and 18F-FAPI-04 PET/CT scans from April 2022 to October 2023. The pathological diagnosis or clinical follow-up served as the reference standard. The Z-test for two proportions was used to compare the sensitivity, specificity, and accuracy of tumor diagnosis between the two imaging agents. Wilcoxon signed-rank tests were employed to compare the uptake of the two radiotracers and the tumor-to-background ratio (TBR) differences in tumors. The study involved 15 types of tumors and included 88 patients, comprising 53 males and 39 females, with an average age of 57.7 ± 10.8 years. In patient-based analysis, 18F-FAPI-04 PET/CT demonstrated higher diagnostic accuracy than 18F-FDG PET/CT for both initial staging and restaging patients (77.4% vs 56.6%, p = 0.0389; 94.3% vs 54.3%, p < 0.001), prompting treatment plan adjustments in 17% of restaged patients. The lesion-based analysis revealed comparable diagnostic accuracy of 18F-FAPI-04 PET/CT and 18F-FDG PET/CT for primary tumors (78.9% vs 75.4%, p = 0.8234), while showing superior accuracy for residual/recurrent tumors, lymph node metastases, and distant metastases compared to 18F-FDG PET/CT (100.0% vs 50.0%, p = 0.002; 98.8% vs 86.0%, p < 0.001; 98.3% vs 79.3%, p < 0.001). 18F-FAPI-04 PET/CT exhibits higher uptake and TBR in most tumors demonstrating superior diagnostic efficacy for primary lesions, residual/recurrent disease, and metastases compared to 18F-FDG PET/CT, particularly beneficial for restaging post-treatment patients.

Enhancing corneal ectasia susceptibility detection: analysis of a new algorithm (BAD-D v4)

Accurate detection of post-refractive ectasia susceptibility is essential during preoperative evaluation for laser vision correction (LVC) due to the risk of progressive corneal ectasia and vision decline post-surgery. Despite improved screening and a reduced incidence from 0.66 to 0.033%, iatrogenic ectasia remains a concern due to the severe vision loss it can cause, highlighting the need for more accurate detection tools. A new optimized version of the Belin/Ambrósio Enhanced Ectasia Display version 4 (BAD-D v4) was developed and validated across 26 international centers to enhance the detection of keratoconus and very asymmetric ectasia and to assess the risk of post-refractive ectasia. Analyzing a dataset of 3,886 eyes from 3,351 patients, including normal, keratoconus (KC), and cases with very asymmetric ectasia (VAE) categories, having one eye with normal topography (VAE-NT and the fellow eye with clinical ectasia (VAE-E). The study utilized an optimized logistic regression algorithm improving diagnostic accuracy. The BAD-D v4 showed superior efficacy in differentiating normal eyes from ectatic conditions, with Area Under the Receiver Operating Characteristic Curve (AUROC) scores of 0.997 and 0.998 in training and testing samples for normal versus clinical ectasia. Additionally, in Normal vs. Disease (KC + VAE), the AUROC was 0.974 and 0.966, and in the challenging Normal vs. VAE-NT diverse group, it scored 0.905 and 0.858. These results outperformed the current version (BAD-D v3) and were comparable to the Pentacam Random Forest Index in all tested scenarios, highlighting the potential of BAD-D v4 in early ectasia detection, without altering the index scale or the end-user experience.

Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis

BackgroundSepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis.ResultsSepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival.ConclusionsTreatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis.

Antibacterial Activity and Action Mechanism of Synthetic Interleukin-8 Derived Peptides Against Flavobacterium psychrophilum.

In Chile, Atlantic salmon and rainbow trout face significant production challenges due to the presence of Flavobacterium psychrophilum, which generates severe disease issues and economic losses. To address this, the salmon industry relies on vaccines and antibiotics, the latter raising concerns about bacterial resistance. For that reason, our study explores an alternative strategy for controlling F. psychrophilum infections based on host defence peptides. We previously identified and characterised IL-8-derived salmonid peptides (ssIL-8α and omIL-8α) with potential antimicrobial properties. In the current study, we further investigated the antibacterial activity and mechanism of action of these peptides against F. psychrophilum. First, we demonstrated the antibacterial activity of ssIL-8α and omIL-8α synthetic peptides. Then we evaluated the effects of these peptides on membrane fluidity and localisation on bacterial cells by fluorescence microscopy as well as its impact on bacterial morphology and ultrastructure by electron microscopy. The results indicate that the ssIL-8α at 30 μM exhibits superior efficacy in inhibiting the growth of F. psychrophilum. Also, both ssIL-8α and omIL-8α can bind to pathogen membrane, but ssIL-8α exhibits a higher binding capacity compared to omIL-8α against F. psychrophilum. omIL-8α exhibited the ability to induce early membrane alterations within 15 min, at concentrations of 15 or 30 μM. The SEM and TEM micrographs showed membrane disruption of the bacteria after incubation with ssIL-8α or omIL-8α. However, the damage was more pronounced in the ssIL-8α treatment, as evidenced by a complete detachment of the outer membrane after a 20-min exposure of F. psychrophilum. This study reveals that these peptides significantly alter bacterial membrane morphology, leading to bacterial death, highlighting their potential as alternative treatments in flavobacterial disease control. This work contributes to understanding host defence peptides' role in combating bacterial infections and reducing antibiotic resistance in aquaculture.

The influences of X-rays irradiation on sensory attributes and physicochemical properties of shiitake mushrooms during storage

Shiitake mushrooms (Lentinus edodes) are edible mushrooms with unique flavor and high nutritional value that are is highly perishable and prone to rapid quality deterioration post-harvest. This research evaluated the efficiency of X-rays irradiation to maintain the sensory attributes and physicochemical properties of shiitake mushrooms. Changes in postharvest quality were monitored in irradiated (0.5, 1.0, and 1.5 kGy) mushrooms stored for 35 days. Results indicated that X-rays irradiation effectively mitigated the deterioration in appearance, color and texture of shiitake mushrooms during storage. Electronic nose (E-nose) assay revealed that 0.5 kGy X-rays delayed the aroma fading of shiitake mushrooms while higher doses of X-rays treatment changed the odor profile. After X-rays treatment, the microorganism growth was inhibited, the electrolyte leakage and malondialdehyde (MDA) accumulation were alleviated, and the contents of soluble proteins, reducing sugars, ascorbic acid (AA), and total phenols (TP) were maintained. Notably, 0.5 kGy X-rays irradiation performed superior efficacy in maintaining sensory scores and tissue structure. The study suggests that 0.5 kGy X-rays irradiation can be used as shiitake mushrooms preservation method to retain the perceptual attributes and protect against spoilage.

Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review

BackgroundPropranolol, a nonselective β-blocker, is the first-line treatment for infantile hemangioma (IH). Topical timolol has recently been proposed as a novel IH treatment with fewer adverse effects. This study was conducted to compare the efficacy and safety of oral propranolol and topical timolol for treating IH.MethodsStudies were included after searching PubMed, Embase, Web of Science, and the Cochrane Library via the keywords of “propranolol”, “timolol”, “infantile hemangioma” and their synonyms. A meta-analysis with pooled odds ratios was performed using the fixed-effect model.ResultsSeven articles with 2071 patients were included in this meta-analysis. Compared with topical timolol, oral propranolol had a greater response rate (OR = 2.12, P &amp;lt; 0.001), but it was also associated with a greater risk of adverse events (OR = 2.31, P &amp;lt; 0.001). For superficial IH, timolol demonstrated similar efficacy to propranolol (OR = 1.28, P = 0.34) but with fewer adverse events (OR = 2.30, P = 0.001). Additionally, compared with topical timolol, propranolol at a dosage of 2 mg/kg/d had a better response rate (OR = 2.62, P &amp;lt; 0.001), whereas the 1.0∼1.5 mg/kg/d propranolol group showed no significant difference (OR = 1.34, P = 0.38).ConclusionOral propranolol presents superior therapeutic efficacy in the treatment of IH compared to topical timolol. However, topical timolol can serve as an alternative to oral propranolol for treating superficial IH, providing similar efficacy with fewer adverse effects. Additionally, propranolol at a dosage of 2 mg/kg/d offers greater efficacy with a comparable safety profile, whereas the 1.0∼1.5 mg/kg/d propranolol dosage shows no significant difference in efficacy compared to timolol but is associated with more adverse events.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024603724, identifier CRD42024603724.

Allocating New Slots in a Multi-Airport System Based on Capacity Expansion

Over time, the rapid expansion of civil aviation infrastructure has led to the establishment of multi-airport systems (MASs) or Metroplex, where airports situated in close proximity form interconnected networks. Given that individual airport capacities often fall short of meeting flight scheduling demands, devising effective multi-airport flight scheduling methods becomes imperative. This article introduces a novel MAS slot expansion configuration framework centered on coupling terminal areas. In contrast to conventional airport capacity slot expansion approaches, this framework demonstrates superior configurational efficacy within respective airport terminal environments. The model outlined in this research identifies the terminal control sector as the pivotal resource node within the interconnected terminal area, aiming to maximize the total expanded slots while minimizing the overall unfairness among airports within the terminal airspace. Employing the ε-constraint method facilitates the transformation of the minimization objective into solvable constraint conditions. Subsequently, leveraging Beijing Metroplex as a case study, the research devises benchmark, single-airport, multi-airport minimum, and multi-airport maximum scenarios to compare and analyze configuration outcomes in terms of key resource allocation impacts and coupled resource utilization efficiencies. Ultimately, employing the AirTOp fast-time simulation model validates each scenario, demonstrating that the proposed configuration method yields reduced delay levels and fewer conflicts in simulation environments.

Ultrasound Treatment Combined with Rhamnolipids for Eliminating the Biofilm of Bacillus cereus

Biofilm formation by Bacillus cereus is a major cause of secondary food contamination, leading to significant economic losses. While rhamnolipids (RLs) have shown effectiveness against Bacillus cereus, their ability to remove biofilms is limited when used alone. Ultrasound (US) is a non-thermal sterilization technique that has been found to enhance the delivery of antimicrobial agents, but it is not highly effective on its own. In this study, we explored the synergistic effects of combining RLs with US for biofilm removal. The minimum biofilm inhibitory concentration (MBIC) of RLs was determined to be 32.0 mg/L. Using a concentration of 256.0 mg/L, RLs alone achieved a biofilm removal rate of 63.18%. However, when 32.0 mg/L RLs were combined with 20 min of US treatment, the removal rate increased to 62.54%. The highest biofilm removal rate of 78.67% was observed with 256.0 mg/L RLs and 60 min of US exposure. Scanning electron microscopy analysis showed that this combined treatment significantly disrupted the biofilm structure, causing bacterial deformation and the removal of extracellular polymeric substances. This synergistic approach not only inhibited bacterial metabolic activity, aggregation, and adhesion but also reduced early biofilm formation and decreased levels of extracellular polysaccharides and proteins. Furthermore, US treatment improved biofilm permeability, allowing better penetration of RLs and interaction with bacterial DNA, ultimately inhibiting DNA synthesis and secretion. The combination of RLs and US demonstrated superior biofilm removal efficacy, reduced the necessary concentration of RLs, and offers a promising strategy for controlling biofilm formation in the food industry.

Synergistic effects of neuroprotective drugs with intravenous recombinant tissue plasminogen activator in acute ischemic stroke: A Bayesian network meta-analysis.

Neuroprotective drugs as adjunctive therapy for adults with acute ischemic stroke (AIS) remains contentious. This study summarizes the latest evidence regarding the benefits of neuroprotective agents combined with intravenous recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis. This study conducted a structured search of PubMed, the Cochrane Library, EMBASE, Wanfang Data, and CNKI databases from their inception to March 2024. Grey literature was also searched. The outcomes included efficacy (National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score) and safety (rate of adverse reactions). A total of 70 randomized controlled trials were selected for this network meta-analysis (NMA), encompassing 4,140 patients with AIS treated using different neuroprotective agents plus RT-PA, while 4,012 patients with AIS were in control groups. The top three treatments for NIHSS scores at the 2-week follow-up were Edaravone Dexborneo with 0.9 mg/kg rt-PA, Edaravone with 0.9 mg/kg rt-PA, and HUK with 0.9 mg/kg rt-PA. HUK with 0.9 mg/kg rt-PA, Dl-3n-butylphthalide with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA were ranked the top three for BI scores at the 2-week follow-up. The top three treatments with the lowest adverse effect rates were 0.6 mg/kg rt-PA, HUK with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA due to their excellent safety profiles. Compared to rt-PA alone, the combination treatments of Edaravone+rt-PA, Edaravone Dexborneol+rt-PA, HUK+rt-PA, Dl-3n-butylphthalide+rt-PA, and Ganglioside GM1+rt-PA have shown superior efficacy. This NMA suggest that combination therapies of neuroprotective agents and rt-PA can offer better outcomes for patients with AIS. The results support the potential integration of these combination therapies into standard AIS treatment, aiming for improved patient outcomes and personalized therapeutic approaches.

Integrating AI and ML for Enhanced Homeopathic Management of Canine Epilepsy

Canine epilepsy, a prevalent neurological disorder, poses significant challenges in veterinary medicine. Traditional treatment approaches often yield variable outcomes, necessitating exploration of alternative therapies. This study investigates the efficacy of homeopathic remedies in managing canine epilepsy and explores the potential of Artificial Intelligence (AI) and Machine Learning (ML) to enhance treatment protocols. We analyzed data from 32 epileptic dogs, documenting various parameters including age, breed, sex, weight, seizure frequency and duration pre- and post-treatment, homeopathic remedies used, potency, treatment duration, and owner observations. Remedies included Agaricus mus, Belladonna, Cicuta virosa, Cina, Hyoscyamus, Cuprum met and Natrum mur, administered in potencies of 30C, 200C, 1M and 0/1 LM over treatment durations ranging from 2 to 24 months. Descriptive statistics and visualizations revealed significant findings. Bulldogs and male dogs exhibited the highest improvement levels, particularly with Agaricus mus and Natrum mur remedies. Notably, remedies administered at LM potencies (0/1 LM) and longer durations (21 months) demonstrated superior efficacy. Improvement levels during treatment showed moderate correlations with treatment duration, indicating prolonged administration enhances therapeutic outcomes. We trained 3 different ML algorithms logistic regression, random forest and xgboost. The Random Forest model emerged as the most accurate, with an accuracy of 86%. Feature importance analysis revealed that pre-treatment seizure frequency, homeopathic remedy used, and treatment duration were critical predictors of treatment success In conclusion, Integrating AI and ML can revolutionize this aspect by analyzing large datasets to predict optimal treatment protocols based on individual patient characteristics. Machine learning algorithms can identify patterns and correlations that may not be immediately apparent, offering insights into the most effective remedies, potencies, and durations for specific breeds and demographics. This approach promises to enhance the quality of life for affected dogs and provide veterinarians with robust tools for decision-making.

High-efficiency PMS activation by difunctional Co-Fe PBA/g-C3N4 S-scheme heterojunction for oxytetracycline degradation: Performance evaluation and mechanism insight

The utilization of sulfate radical-based advanced oxidation processes (SR-AOPs) has captivated the academic community due to their minimal energy requirements and superior efficacy in peroxomonosulfate (PMS) activation for pollutant decomposition. Notwithstanding these advantages, engineering an effective and economical catalyst for PMS activation presents a considerable hurdle. In the present study, a metal-organic framework of CoFe PBA is ingeniously anchored onto g-C3N4 nanosheets, resulting in the formation of an innovative CoFe PBA/g-C3N4 S-scheme heterojunction that demonstrates remarkable efficiency in PMS activation. Intriguingly, the catalytic efficiency of CoFe PBA/g-C3N4 surpasses that of g-C3N4 and CoFe PBA by 7-fold and 2.33-fold, respectively. The heightened activity of CoFe PBA/g-C3N4 heterojunction is attributed to the enhanced charge transfer efficiency, a consequence of the successful heterojunction formation. Concurrently, the ability of photoexcited electrons to reduce Co3+/Fe3+ to Co2+/Fe2+ bolsters PMS activation. Significantly, this heterojunction retains unparalleled stability in degrading oxytetracycline without discernible performance attenuation, heralding its commendable prospects in real-world applications. Besides, mechanism exploration indicates that SO4−, h+, and electron transfer contribute to oxytetracycline degradation in the CoFe PBA/g-C3N4 system. This investigation serves as a beacon for the strategic development of highly active and stable catalysts for PMS activation, aiming at environmental decontamination.

Influence of V/B ratio and rolling treatment on the grain refinement efficacy and anti-fading ability of Al-V-B master alloys

As a promising anti Si-poisoning grain refiner, Al-V-B master alloys have gained increasing attention in the past several years. However, the effect of V:B ratio on the grain refinement effect, as well as the refining mechanism has not been clearly investigated. This work investigates the impact of V:B ratio on microstructures of Al-V-B master alloys and grain refinement efficacy for α-Al grains in AlSi alloys. In addition, the effect of rolling treatment on the agglomeration and sedimentation of Al-V-B master alloys has been investigated. It demonstrates that the V:B ratio significantly affects primary secondary phases within Al-V-B master alloys, with an optimal ratio of 2.33 (Al-4.2 V-1.8B) leading to the finest average α-Al grain size of ~98 μm in the Al8Si alloy. Moreover, rolling treatment further enhances the grain refinement efficacy of Al-4.2 V-1.8B master alloy by dispersing VB2 agglomerates/particles and reducing agglomeration and sedimentation during smelting. Accordingly, the rolled Al-4.2 V-1.8B master alloy reduces the average α-Al grain size to ~75 μm at only 50 % amount of the as-cast Al-4.2 V-1.8B master alloy, improving the grain refinement efficacy by 25 % (75 μm v.s. 98 μm). At the same time, the rolled Al-4.2 V-1.8B master alloy exhibits exceptional anti-fading ability, maintaining a stable grain refinement efficacy for up to 120 min. Cs-corrected transmission electron microscopy (TEM) reveals that VB2 particles act as primary nucleation sites for α-Al grains, with a specific crystallographic orientation relationship: [1 1 2¯ 0] (0001) VB2 || [1¯ 1 0] (111) α-Al. This study provides valuable insights into the design of Al-V-B master alloys with superior grain refinement efficacy and anti-fading ability for AlSi alloys.

Removal of tetracycline using an ultrastable Pt-decorated-BNCB photocatalyst under efficient solar-driven conditions

The pursuit of optimizing the photocatalytic performance of the novel perovskite-like Bi4NbO8X materials remains a vibrant area of research. In this paper, we report the successful synthesis of the Bi4Nb4O8Cl0.935Br0.065 (BNCB) composite photocatalyst, loaded with Pt nanoparticles, utilizing a combination of solid-state reaction and sodium borohydride reduction methods. Notably, the surface plasmon resonance (SPR) effect exhibited by Pt broadened the spectral response range, while the Schottky junction formed at the Pt/BNCB interface significantly accelerated the separation of photogenerated electron-hole pairs and facilitated the swift migration of photogenerated electrons towards Pt. Experimental outcomes underscore the superior photocatalytic degradation efficacy of the Pt/BNCB composite towards tetracycline (TC), achieving a degradation rate of up to 67%, significantly outperforming pure BNCB. Pt/BNCB exhibits excellent photocatalytic degradation and excellent stability in various pH and ionic environments. Collectively, this work presents a novel approach for designing highly efficient and stable perovskite-type photocatalytic materials, holding immense potential for applications in environmental remediation.

A retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and in vitro assessment of three antiviral compounds

Since the beginning of May 2022, cases of mpox have been reported in several European and American countries where the disease is nonendemic. We performed a retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and assessed the invitro sensitivity of three antiviral compounds to a monkeypox virus (MPXV) strain from the 2022 outbreak. We sequenced the complete genomes of MPXV isolated from skin-, throat-, anorectal- and genital swab samples using the Oxford Nanopore Technologies (ONT) GridION. We subsequently analysed high-quality complete MPXV genomes and conducted a genomic analysis of MPXV complete genomes from this study with all other complete MPXV genomes available on GISAID up to October 28th, 2022. The invitro activity of tecovirimat, brincidofovir, and cidofovir was also tested in human and monkey cell lines. We produced 248 complete MPXV genomes. Phylogenetic analysis of the complete MPXV genomes revealed that they all belong to MPXV Clade IIb B.1. Surprisingly, through phylogeographic analysis we identified a minimum number of 79 introduction events into Belgium, along with sustained local transmission. We also demonstrated the superior invitro efficacy and selectivity of tecovirimat to the 2022 MPXV clinical strain. The number of sequences provides sufficient information about the MPXV lineages that were circulating in Belgium. The 2022 mpox outbreak, in Belgium, was mainly characterised by many introduction events that were promptly contained and resulted in limited human-to-human transmission of MPXV. The invitro efficacy of antivirals against a 2022 MPXV Belgian strain highlights the potent activity and specificity of tecovirimat and its ability to prevent the formation of the extracellular enveloped viruses. None.

Multi-agent reinforcement learning with synchronized and decomposed reward automaton synthesized from reactive temporal logic

Multi-agent systems (MAS) consist of multiple autonomous agents interacting to achieve collective objectives. Multi-agent reinforcement learning (MARL) enhances these systems by enabling agents to learn optimal behaviors through interaction, thus improving their coordination in dynamic environments. However, MARL faces significant challenges in adapting to complex dependencies on past states and actions, which are not adequately represented by the current state alone in reactive systems. This paper addresses these challenges by considering MAS operating under task specifications formulated as Generalized Reactivity of rank 1 (GR(1)). These synthesized strategies are used as a priori knowledge to guide the learning. To tackle the difficulties of handling non-Markovian tasks in reactive systems, we propose a novel synchronized decentralized training paradigm that guides agents to learn within the MARL framework using a reward structure constructed from decomposed synthesized strategies of GR(1). We initially formalize the synthesis of GR(1) strategies as a reachability problem of winning states of the system. Subsequently, we develop a decomposition mechanism that constructs individual reward structures for decentralized MARL, incorporating potential values calculated through value iteration. Theoretical proofs are provided to verify that the safety and liveness properties are preserved. We evaluate our approach against other state-of-the-art methods under various GR(1) specifications and scenario maps, demonstrating superior learning efficacy and optimal rewards per episode. Additionally, we show that the decentralized training paradigm outperforms the centralized training paradigm. The value iteration strategy used to calculate potential values for the reward structure is compared against two other strategies, showcasing its advantages.

Omega-3 polyunsaturated fatty acids protect against cisplatin-induced nephrotoxicity by activating the Nrf2 signaling pathway

Nephrotoxicity is a prevalent side effect observed in patients undergoing chemotherapy. The pathogenesis of chemotherapy-induced nephrotoxicity involves various factors such as oxidative stress, DNA damage, inflammation, and apoptosis. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess anti-inflammatory and antioxidant properties. This study investigated the effects of EPA and DHA, either alone or in combination, on cisplatin-induced nephrotoxicity in mice, as well as their underlying mechanisms of action. The combined administration of EPA and DHA demonstrated superior efficacy in mitigating cisplatin-induced nephrotoxicity compared to administration alone, including the reduction of oxidative damage, inflammation, and apoptosis. Moreover, the combination of EPA and DHA suppressed inflammation and prevented the development of chronic kidney fibrosis during prolonged observations following repeated cisplatin administration. Mechanistically, ω-3 PUFAs enhance the expression of antioxidant genes by activating the p62-Keap1-Nrf2 signaling pathway. Furthermore, Nrf2 activation can inhibit the cisplatin-induced p53 apoptosis signal by upregulating the expression of MDM2 in renal tubular epithelial cells. Consequently, ω-3 PUFAs exert a protective effect against cisplatin-induced renal injury through activating the Nrf2 signaling pathway, suggesting that ω-3 PUFAs intake holds promise as a therapeutic strategy for combating cisplatin-induced nephrotoxicity.

Protective effects of insoluble dietary fiber from cereal bran against DSS-induced chronic colitis in mice: From inflammatory responses, oxidative stress, intestinal barrier, and gut microbiota.

Insoluble dietary fiber (IDF) is a crucial component of cereals, and IDF from cereal bran (IDF-CB) has been reported to have multiple biological activities. However, the effect of IDF-CB on chronic colitis remains underexplored. The study aimed to investigate the impact of IDFs from wheat bran (WBIDF), rice bran (RBIDF), millet bran (MBIDF) and oat bran (OBIDF) on chronic colitis induced by dextran sulfate sodium (DSS). Our findings demonstrated that IDFs-CB supplementation mitigated DSS-induced weight loss and reduced lesions in the colon and spleen. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and oxidative stress markers (MPO, iNOS and MDA)were decreased, and anti-inflammatory cytokine (IL-10) and T-SOD activity were increased after IDF-CB inclusion. Furthermore, IDFs-CB restored intestinal barrier function by regulating gene expression (up-regulated Muc-2, ZO-1 and Occludin, and down-regulated Claudin-1 and Claudin-4). Additionally, we analyzed the gut microbiota and SCFAs composition. WBIDF, MBIDF and OBIDF inhibited the growth of Muribaculaceae_unclassified, Bacteroides and Parasutterella. Conversely, IDFs-CB promoted the growth of Candidatus_Saccharimonas and norank_f__norank_o__Clostridia_UCG-014. Notably, WBIDF enhanced the abundance of Allobaculum, while MBIDF and OBIDF increased the abundance of Lachnospiraceae_NK4A136. Moreover, supplementation with IDFs-CB significantly elevated certain SCFA concentrations-particularly acetic acid and isohexanoic acid. Our results suggested that IDF-CB effectively alleviated DSS-induced chronic colitis; among them，WBIDF exhibited superior efficacy followed by OBIDF，MBIDF，and RBIDF. This study provides a theoretical foundation for dietary recommendations for patients suffering from inflammatory bowel disease.

Plant-derived extracellular vesicles release combined with systemic DOX exhibits synergistic effects in 3D bioprinted triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking targeted therapeutic options. Hydrogels, particularly gelatin methacrylate (GelMA), have emerged as promising materials for localized drug delivery due to their biocompatibility and tunable properties. This study investigates a dual-delivery system for enhancing the treatment efficacy of triple-negative breast cancer (TNBC) using a combination of extracellular vesicles (EVs) derived from Citrus limon L. and the chemotherapeutic drug doxorubicin (DOX). We fabricated 3D bioprinted GelMA scaffolds to achieve localized and controlled release of EVs and evaluated their synergistic effects with systemic DOX delivery on both primary and metastatic 3D TNBC models.The GelMA scaffolds, especially those with 95 % methacrylation, exhibited higher stiffness, which enhanced their sustained release. Following 48-h incubation, the combination of EVs and DOX significantly increased cytotoxicity in the primary 3D TNBC model, reducing cell viability to approximately 30 % compared to controls. This was notably more effective than treatments with DOX or EVs alone. During the extended 7-day incubation period, the combination treatment continued to show superior efficacy, with persistently high levels of ROS generation and further reduction in cell viability. In a metastatic 3D TNBC model, a significant sensitivity to the combined treatment was observed, which notably inhibited aggregate formation and migration. Importantly, EVs-embedded scaffolds promoted the proliferation of human fibroblasts, highlighting their non-toxic nature, while concurrently inhibiting TNBC cell growth. This approach provides a promising strategy to improve the treatment outcomes of TNBC by exploiting the synergistic effects of local EVs release and systemic chemotherapy.

Interleukin-6 Inhibitors for Neuromyelitis Optica Spectrum Disorder (NMOSD): a Systematic Review and Meta-analysis

BackgroundInterleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD). ObjectiveWe performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD. MethodsWe searched PubMed, Embase, and Cochrane Central for eligible studies. Efficacy endpoints included hazard ratio (HR) for relapse, annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) change over time. Safety outcomes comprised any adverse event, serious adverse events and infections. Statistical analysis was performed using RevMan Web and R studio package meta. Heterogeneity was assessed with I² statistics. ResultsFour studies involving 361 patients (228 treated with IL-6 inhibitors) were included. IL-6 inhibitors significantly reduced HR for relapse (HR 0.35; 95% CI 0.23, 0.55); p<0.00001; I²=0%) and ARR (mean difference -0.79 relapses/year; 95% CI -1.54, -0.03; p=0.04; I²=96%) compared to placebo or traditional immunosuppressants. No significant differences were observed in EDSS change over 24 weeks of follow-up (mean difference -0.18; 95% CI 0.41, 0.05; p=0.93; I²=0%), adverse events (odds ratio (OR) 1.59; 95% CI 0.45, 5.63; p=0.48; I²=48%), serious adverse events (OR 0.76; 95% CI 0.40, 1.44; p=0.50; I²=0%) and infection rates (OR 1.10; 95% CI 0.67, 1.79; p=0.71; I²=0%). ConclusionIL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks.

Clinical Efficacy of Ezetimibe Combined with Rosuvastatin in the Treatment of Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Therapy

Aims/Background Primary hypercholesterolemia (PHC) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Although the fact that statins effectively lower low-density lipoprotein cholesterol (LDL-C) levels, some patients fail to achieve target LDL-C levels and continue to have a high risk of cardiovascular disease. This study aims to evaluate the clinical efficacy and safety of ezetimibe combined with rosuvastatin in patients with PHC. Methods This study retrospectively examined 101 patients with PHC who received statins at the cardiology department of Jilin Province FAW General Hospital, between 2021 and 2024. Patients were divided into the observation (ezetimibe combined with rosuvastatin, n = 45) and control (rosuvastatin, n = 66) groups in accordance with their treatment regimens. Data were sourced from the hospital's electronic health records system, and statistical analysis was performed by using SPSS 25.0 software (IBM Corporation, Armonk, NY, USA). Results Baseline characteristics were similar between the two groups. After 12 weeks of treatment, the reduction in LDL-C levels in the observation group (–0.373 [–0.427, –0.348]) was greater than that in the control group (–0.240 [–0.318, –0.222], p &lt; 0.001). The percentage changes in total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were significantly better in the observation group (TC: –0.230 [–0.302, –0.144], TG: –0.292 [–0.333, –0.237], and HDL-C: 0.081 [0.067, 0.111]) than in the control group (TC: –0.127 [–0.158, –0.119], TG: –0.082 [–0.101, –0.067], and HDL-C: 0.000 [–0.163, 0.133] with p &lt; 0.001, p &lt; 0.001, and p = 0.011, respectively). Regarding drug safety, the incidence of adverse events was comparable between the two groups (11.10% vs. 12.10%, p = 0.871). Conclusion The combination of ezetimibe and rosuvastatin demonstrates superior lipid-lowering efficacy and good safety in patients with PHC inadequately controlled by statin therapy, providing an effective alternative treatment option. Further large-scale, multicenter randomized controlled trials are warranted to confirm its long-term efficacy and safety.