PLoS ONE最新文献

Studying limited datasets derived from complex interacting systems, such as neural population activity, represents an important and challenging task. The level of detail in recorded activities is highly influenced by the temporal resolution at which the activities are studied. However, does more detail always lead to a correct assessment of the system? This study examines how temporal resolution influences the inference of higher-order statistical dependencies and information representation in population-level neuronal activity. Using a minimally biased data-driven statistical inference framework, minimally complex models, we studied grid cell populations in the medial entorhinal cortex across a broad range of temporal resolutions. Results based on 23 grid cell recordings including different animals and behavioral states show that at an intermediate temporal resolution (𝒪(102)  ms), the inferred model captures significant higher order dependencies alongside efficient information representations, whereas the finest and the coarsest temporal resolutions lead to poor information representation. The informative temporal resolution can be identified by two criteria: the bin size at which the inferred interaction structure is most consistent across population sizes, and the peak of the model's information representations, which agree closely across recordings. These findings indicate that temporal resolution is a critical factor in the inference of higher order neural structure and highlight that resolution-aware modeling is crucial for accurate analysis and characterization of collective dynamics in complex neuronal systems.

Maggot therapy uses necrophagous dipteran larvae to remove necrotic tissue, requiring strict aseptic protocols. The disruption of egg masses is a crucial step to ensure uniform disinfection; however, chemical agents can cause sublethal effects. This study investigated the impact of three disrupting compounds on the post-embryonic development of Chrysomya megacephala and Chrysomya putoria. Egg masses were subjected for 10 minutes to the following treatments: papain (0.5%), sodium hydroxide (NaOH 1%), potassium hydroxide (KOH 2%), and a control (distilled water). After hatching, 40 larvae per replicate (n = 640 per species) were monitored for viability, stage duration, feeding cessation rate, larval weight (L3), sex ratio, and morphological normality. Data normality was assessed using the Shapiro-Wilk test; comparisons between treatments were performed using nonparametric Kruskal-Wallis tests followed by Dunn's post hoc tests, while categorical variables were analyzed using chi-square tests and Fisher's exact test, with a significance level of p < 0.05. The results revealed species-specific responses. In Chrysomya megacephala, there was no significant reduction in viability (57% to 70%) or changes in the pupation rate among the groups. However, NaOH significantly reduced larval weight (67.5 mg) compared to the control (69.9 mg), while papain did not differ significantly from the control (68.5 mg). Chrysomya putoria, on the other hand, showed greater sensitivity to alkaline compounds; treatments with NaOH and KOH reduced total viability to 68% (compared to 88-91% in the control and papain groups) and delayed the feeding cessation rate. In both species, papain preserved larval weight gain and maintained developmental stability. The total duration of the life cycle (10-11 days) and the morphological normality of adults were not significantly affected by the treatments. It is concluded that C. megacephala exhibits greater physiological resilience to chemical stress in early life stages. Among the agents tested, 0.5% papain emerged as the most promising option for maggot therapy protocols, as it combines efficient dissociation with the maintenance of larval biological quality.

Purpose: We assessed the safety and efficacy of magnetic resonance (MR)-guided microwave ablation for treating hepatic malignancies.

Methods: This retrospective single-center review evaluated patients who underwent MR-guided microwave ablation for hepatic malignancies between 02/15/2017-04/22/2020. Complications were classified following CIRSE guidelines. Local tumor progression (LTP), local tumor recurrence (LTR), non-target progression (NTP), progression-free survival (PFS) and time to progression (TTP) were assessed, with data presented as mean ± standard deviation.

Results: Sixteen patients (60.75 ± 14.4 years; 9 males, 7 females) underwent 17 MR-guided microwave ablation for 21 hepatic malignancies (17 (81.0%) hepatocellular carcinoma, 1 (4.8%) cholangiocarcinoma, 2 (9.5%) metastases, and 1 (4.8%) suspicious lesion in a patient with primary sclerosing cholangitis). Lesion size was 12.2 ± 4.8 mm and total procedure time 138 ± 53 minutes. Complications included fever (N = 2), abdominal pain (N = 2), biloma (N = 1), and reactive cholecystitis (N = 1). These resolved with pain medication for one patient and antibiotics for another. No tumor recurrence was observed at ablation sites (LTP and LTR = 0%) at 36.7 ± 28.2 months. NTP occurred in 11 patients (68.8%) with a TTP of 14.8 ± 11.4 months. PFS was 44 months (95% CI: 10-85 months). Three patients died during follow-up - one from complications after liver transplantation and two from disease progression. Post-ablation liver transplantation was performed in two patients.

Conclusion: MR-guided microwave ablation for hepatic malignancies is safe and effective, with no local tumor recurrences noted over a follow-up period of 36.7 ± 28.2 months.

Clinical significance: MR-guided microwave ablation is a promising minimally invasive treatment for hepatic malignancies, demonstrating no LTR at 36.7 ± 28.2 months. Precise, radiation-free needle placement in real-time and effective targeting of small tumors may further improve future patient care.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease with a high degree of cellular heterogeneity and molecular complexity, characterized pathologically by persistent airflow limitation and an inflammatory-tissue remodeling cascade involving multiple cell types. Traditional transcriptomics lack the resolution to precisely define cell subpopulation roles in COPD. Single-cell RNA sequencing (scRNA-seq) overcomes this limitation by enabling high-resolution analysis of cell-type-specific mechanisms in COPD. A total of 101,009 cells from three scRNA-seq datasets were integrated to profile COPD-related molecular features and cell interactions at single-cell resolution. Analysis identified four major cell types and 17 distinct cell subtypes. Cell-cell communication analysis revealed a significant reduction in signaling activity of macrophages and fibroblasts, whereas certain immune cells exhibited enhanced signaling, suggesting that immune dysregulation plays a pivotal role in COPD pathogenesis. Further analysis focused on macrophage-dominant myeloid cells and fibroblasts, uncovering their critical roles in inflammation modulation and fibrosis progression. Meanwhile, this study also identified 19 chemicals that may influence COPD progression by modulating cellular gene expression. This study provides an important molecular basis for unraveling the cell-cell interaction network of COPD and elucidating the mechanism of each cell subpopulation in the disease process.

Arterial cannulation for cardiopulmonary bypass in small dogs is challenging because small vessel diameters may preclude use of appropriately sized pediatric arterial cannulas. Although off-label use of 14-gauge hemodialysis catheters has been reported, their pressure-flow characteristics under small-dog cardiopulmonary bypass conditions remain unclear. This in vitro study evaluated one 8-French pediatric arterial cannula and six 14-gauge hemodialysis catheter specimens-separate side-hole and sealed specimens at effective lengths of 25, 32, and 38 mm-in a closed-loop mock circuit for a 3-kg small dog. A 34% (w/w) glycerol-water solution (viscosity 2.8 cP at 28°C) served as an approximate Newtonian blood analogue. The Stockert S5 pump flow-rate setting was increased from 50 to 350 mL/min; 50-300 mL/min was prespecified as the primary analysis range and 350 mL/min as exploratory. The reported outlet pressure was recorded 1,000 mm upstream of the test device, while inlet pressure was monitored 300 mm downstream and regulated to 60 mmHg; six technical runs per condition were conducted using the same physical device and circuit setup. Within the primary analysis range, outlet pressure was approximately 136-137 mmHg at 300 mL/min; mean differences for the 14-G specimens versus the 8-French cannula were +0.33 to +0.67 mmHg, with 95% confidence intervals from -1.33 to +2.15 mmHg. At 350 mL/min, outlet pressures were higher for all three side-hole 14-gauge specimens than for the 8-French cannula. At 300 mL/min, outlet pressure was approximately 2-3 mmHg lower for the side-hole specimens than for the sealed specimens across all catheter lengths. Together, these findings indicate small observed circuit-level differences in outlet pressure among tested devices within this standardized mock small-dog cardiopulmonary bypass circuit, but do not establish formal equivalence, device-to-device interchangeability, or clinical validity.

An increase in metabolomics research over the last decade has expanded species-specific knowledge of biological processes, but has primarily focused upon humans, domesticated and model animal species. Recent advances, particularly around data management pipelines for untargeted studies, make the field more accessible to disciplines outside those embedded in analytical chemistry, including wildlife conservation. To establish the breadth of existing wild vertebrate animal metabolomic research, specifically utilising non-invasive sampling, this scoping review establishes: (1) general trends in publication numbers; (2) coverage of wildlife taxonomic groups and species; (3) subject numbers and sample size; (4) non-invasive sample types; (5) metabolomic techniques utilised; (6) the context of current literature and (7) conservation implications. This scoping review was conducted following the JBI methodology and reported in accordance with PRISMA-ScR; searches were conducted using PubMed, Scopus, Web of Science and supplemented with Google Scholar; following screening, 83 peer-reviewed original research papers were identified using predefined criteria and data extracted. The most popular areas of research were physiology and reproduction (30%) and diet and nutrition (27%). Although most publications focused on a single species, there were 11 multi-species publications, resulting in metabolomics data for 93 species. A large proportion of which, 72%, were mammalian, and of these, 52% are currently listed at risk of extinction on the IUCN Red List. With over 60% of all publications published between 2022-2025, non-invasive vertebrate wildlife metabolomics appears to be gaining traction as a tool in wildlife physiology research. However, future research would benefit from alignment with model animal metabolome research experimental design, as few studies included the consideration of metabolite extraction optimisation, storage conditions, the use of integrated omics platforms beyond microbiome analysis and consideration of statistical power, particularly in respect to intra-individual variation and the characterisation of species-specific metabolomes.

Cross shareholders have become a common phenomenon in capital markets, which increasingly draw the attention of scholars. This paper examines the effect of cross shareholders on corporate cash holdings in Chinese capital market and finds cross shareholders increase corporate cash holdings. Further mechanism analyses find suggestive evidence that this increase is correlated with reductions in overinvestment and improvements in total asset turnover. Additional results show the effect of cross shareholders has heterogeneous significance given the conditions of different external environment and firm characteristics. Moreover, cross shareholders reinforce the positive effect of cash holdings on firm productivity. Overall, this paper's findings provide insight for understanding the role of cross shareholders in corporate cash holding decision in China.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central regulator of low-density lipoprotein (LDL) cholesterol metabolism, yet the functional consequences of many clinically observed PCSK9 variants remain unknown. To establish a rigorous system for quantitative variant assessment, we generated a PCSK9 knockout (KO) HepG2 cell line through CRISPR/Cas9-mediated deletion of exons 2-8, effectively removing both the prodomain and catalytic regions required for PCSK9 function. This null background enabled systematic functional mapping of wild-type (WT) PCSK9 and multiple clinically relevant variants representing well-characterized, recurrent, and previously understudied alleles. Functional assays revealed pronounced heterogeneity among variant activities. The classical gain-of-function (GOF) variants D374Y and R496W exhibited robust suppression of LDL uptake, whereas A443T-an infrequently reported and previously uncharacterized variant-demonstrated a loss-of-function (LOF)-like phenotype with significantly enhanced LDL uptake. Additional poorly characterized variants, including V4I, R104C/V114A, and R496W/N425S, displayed varied functional profiles, providing novel mechanistic insights. Surface LDL receptor (LDLR) levels generally correlated with LDL uptake but revealed unique patterns for specific variants. This KO-based rescue system provides a high-resolution framework for mechanistic classification of both established and poorly characterized PCSK9 variants, bridging the gap between genetic discovery and functional interpretation while supporting precision lipid-lowering strategies.