Bioequivalence and Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study.

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25 mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.

Targeted Radionuclide Therapy in Glioblastoma.

Despite the development of various novel therapies, glioblastoma (GBM) remains a devastating disease, with a median survival of less than 15 months. Recently, targeted radionuclide therapy has shown significant progress in treating solid tumors, with the approval of Lutathera for neuroendocrine tumors and Pluvicto for prostate cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This achievement has shed light on the potential of targeted radionuclide therapy for other solid tumors, including GBM. This review presents the current status of targeted radionuclide therapy in GBM, highlighting the commonly used therapeutic radionuclides emitting alpha, beta particles, and Auger electrons that could induce potent molecular and cellular damage to treat GBM. We then explore a range of targeting vectors, including small molecules, peptides, and antibodies, which selectively target antigen-expressing tumor cells with minimal or no binding to healthy tissues. Considering that radiopharmaceuticals for GBM are often administered locoregionally to bypass the blood-brain barrier (BBB), we review prominent delivery methods such as convection-enhanced delivery, local implantation, and stereotactic injections. Finally, we address the challenges of this therapeutic approach for GBM and propose potential solutions.

Genome-wide characterization of RR gene family members in Zanthoxylum armatum and the subsequent functional characterization of the C-type RR.

Response Regulators (RRs) are crucial regulators in plant development and stress responses, comprising A-type, B-type, C-type, and pseudo-RR subfamilies. However, previous studies have often focused on specific subfamilies, which restricts our understanding of the complete RR gene family. In this study, we conducted a comprehensive analysis of 63 RR members from Zanthoxylum armatum, using phylogenetic relationships, motif composition, cis-acting elements, gene duplication and collinearity analyses. Segmental repeats among ZaRR genes enhanced the various environmental adaptabilities of Z. armatum, and the B-type ZaRR exhibited significant collinearity with the RRs in P. trichocarpa and C. sinensis. Cis-element analysis indicated ZaRRs play a significant role in abiotic stress and phytohormone pathways, particularly in light, drought, cold, abscisic acid (ABA) and salicylic acid (SA) responses. Abundant Ethylene Response Factor (ERF) and reproduction-associated binding sites in ZaRR promoters suggested their roles in stress and reproductive processes. A-type ZaRRs were implicated in plant vegetative and reproductive growth, whereas B-type ZaRRs contributed to both growth and stress responses. C-type ZaRRs were associated with plant reproductive growth, whereas pseudo-RRs may function in plant stress responses, such as water logging, cold, and response to ethylene (ETH), SA, and jasmonic acid (JA). Ectopic expression of ZaRR24, a C-type RR, inhibits growth, induces early flowering, and shortens fruit length in Arabidopsis. ZaRR24 overexpression also affected the expression of A- and B-type RRs, as well as floral meristem and organ identity genes. These findings establish a solid and comprehensive foundation for RR gene research in Z. armatum, and provide a platform for investigating signal transduction in other woody plants.

Role of IL-1 Family Cytokines IL-36, IL-37, IL-38 in Osteoarthritis and Rheumatoid Arthritis: A Comprehensive Review.

Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.

Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.

Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic Bacillus amyloliquefaciens has been shown to alleviate the pathological injuries in mice infected with Schistosoma japonicum by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in S. japonicum-infected mice treated with B. amyloliquefaciens. The results revealed that intervention with B. amyloliquefaciens altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of xfp/xpk and genes translated to urease was significantly restored. Further analysis showed that Limosilactobacillus reuteri was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by S. japonicum infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by B. amyloliquefaciens might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica. IMPORTANCE: Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.

Improved mortality prediction for pediatric acute liver failure using dynamic prediction strategy.

OBJECTIVES: To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction. METHODS: Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation. RESULTS: We constructed a prognostic joint model that combines the temporal trajectories of international normalized ratio, total bilirubin, hepatic encephalopathy, platelet count, and serum creatinine. Dynamic prediction using updated information improved predictive performance over static prediction using the information at enrollment (Day 0) only. In cross-validation, AUC increased from 0.784 to 0.887 when measurements obtained between Days 1 and 2 were incorporated. AUC remained similar when we used the earlier subset of the sample for training and the later subset for testing. CONCLUSIONS: Serial measurements of five variables in the first few days of PALF capture the dynamic clinical course of the disease and improve risk prediction for mortality. Continuous disease monitoring and updating risk prognosis are beneficial for timely and judicious medical decisions.

The short-term impact of comprehensive caries treatment on the supragingival microbiome of severe early childhood caries.

BACKGROUND: Children affected by severe early childhood caries (S-ECC) usually need comprehensive caries treatment due to the extensive of caries. How the oral microbiome changes after caries therapy within the short-term warrant further study. AIM: This study aimed to investigate the short-term impact of comprehensive caries treatment on the supragingival plaque microbiome of S-ECC children. DESIGN: Thirty-three children aged 2-4 years with severe caries (dt > 7) were recruited. Comprehensive caries treatment was performed under general anesthesia in one session and included restoration, pulp treatment, extraction, and fluoride application. Supragingival plaque was sampled pre- and 1-month posttreatment. The genomic DNA of the supragingival plaque was extracted, and bacterial 16S ribosomal RNA gene sequencing was performed. RESULTS: Our data showed that the microbial community evenness significantly decreased posttreatment. Furthermore, comprehensive caries treatment led to more diverse microbial structures among the subjects. The interbacterial interactions reflected by the microbial community's co-occurrence network tended to be less complex posttreatment. Caries treatment increased the relative abundance of Corynebacterium matruchotii, Corynebacterium durum, Actinomyces naeslundii, and Saccharibacteria HMT-347, as well as Aggregatibacter HMT-458 and Haemophilus influenzae. Meanwhile, the relative abundance of Streptococcus mutans, three species from Leptotrichia, Neisseria bacilliformis, and Provotella pallens significantly decreased posttreatment. CONCLUSION: Our results suggested that comprehensive caries treatment may contribute to the reconstruction of a healthier supragingival microbiome.

Urinary oxygen tension and its role in predicting acute kidney injury: A narrative review.

Acute kidney injury occurs frequently in the perioperative setting. The renal medulla often endures hypoxia or hypoperfusion and is susceptible to the imbalance between oxygen supply and demand due to the nature of renal blood flow distribution and metabolic rate in the kidney. The current available evidence demonstrated that the urine oxygen pressure is proportional to the variations of renal medullary tissue oxygen pressure. Thus, urine oxygenation can be a candidate for reflecting the change of oxygen in the renal medulla. In this review, we discuss the basic physiology of acute kidney injury, as well as techniques for monitoring urine oxygen tension, confounding factors affecting the reliable measurement of urine oxygen tension, and its clinical use, highlighting its potential role in early detection and prevention of acute kidney injury.

Agreement of zero-heat-flux thermometry with the oesophageal and tympanic core temperature measurement in patient receiving major surgery.

To identify and prevent perioperative hypothermia, most surgical patients require a non-invasive, accurate, convenient, and continuous core temperature method, especially for patients undergoing major surgery. This study validated the precision and accuracy of a cutaneous zero-heat-flux thermometer and its performance in detecting intraoperative hypothermia. Adults undergoing major non-cardiac surgeries with general anaesthesia were enrolled in the study. Core temperatures were measured with a zero-heat-flux thermometer, infrared tympanic membrane thermometer, and oesophagal monitoring at 15-minute intervals. Taking the average value of temperature measured in the tympanic membrane and oesophagus as a reference, we assessed the agreement using the Bland-Altman analysis and linear regression methods. Sensitivity, specificity, and predictive values of detecting hypothermia were estimated. 103 patients and one thousand sixty-eight sets of paired temperatures were analyzed. The mean difference between zero-heat-flux and the referenced measurements was -0.03 ± 0.25 °C, with 95% limits of agreement (-0.52 °C, 0.47 °C) was narrow, with 94.5% of the differences within 0.5 °C. Lin's concordance correlation coefficient was 0.90 (95%CI 0.89-0.92). The zero-heat-flux thermometry detected hypothermia with a sensitivity of 82% and a specificity of 90%. The zero-heat-flux thermometer is in good agreement with the reference core temperature based on tympanic and oesophagal temperature monitoring in patients undergoing major surgeries, and appears high performance in detecting hypothermia.

Crosstalk of cuproptosis-related prognostic signature and competing endogenous RNAs regulation in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a new type of programmed cell death involved in the regulation of neuroendocrine tumors, immune microenvironment, and substance metabolism. However, the role of cuproptosis-related genes (CRGs) in Hepatocellular carcinoma (HCC) remains unclear. METHOD: Through multiple bioinformatics analysis, we constructed a prognostic gene model and competing endogenous RNA (ceRNA) network. The correlation between CRGs and prognosis, immune infiltration, immune checkpoints, microsatellite instability (MSI) and tumor mutational burden (TMB) was analyzed by Kaplan-Meier curve, univariate Cox, multivariate regression, and Spearman's analysis in HCC patients. Besides, the qRT-PCR and immunohistochemistry assays were used to determine prognostic CRGs mRNA and protein expression in HCC. RESULTS: We established a novel 3-gene signature related to CRGs for evaluating the prognosis of HCC patients. HCC patients with high risk scores had a poor prognosis with an area under the curve of 0.737, 0.646, and 0.634 on 1-year, 3-year, and 5-year receiver operating characteristic curves. Significant correlation was observed between prognostic CRGs and immune infiltration, immune checkpoints, MSI and TMB. We also developed five ceRNA networks to regulate the occurrence and progression of HCC. CDKN2A, DLAT, and PDHA1 protein expression was up-regulated in HCC versus normal tissues. Besides, the mRNA expression levels of CDKN2A, DLAT, GLS, and PDHA1 were elevated in the HCC cell lines compared to the normal liver cell lines. CONCLUSIONS: This novel prognostic CRGs signature could be accurately predict the prognosis of patients with HCC. The ceRNA regulatory network might be potential prognostic biomarkers and therapeutic targets for HCC patients.

A comprehensive multimodal dataset for contactless lip reading and acoustic analysis.

Small-scale motion detection using non-invasive remote sensing techniques has recently garnered significant interest in the field of speech recognition. Our dataset paper aims to facilitate the enhancement and restoration of speech information from diverse data sources for speakers. In this paper, we introduce a novel multimodal dataset based on Radio Frequency, visual, text, audio, laser and lip landmark information, also called RVTALL. Specifically, the dataset consists of 7.5 GHz Channel Impulse Response (CIR) data from ultra-wideband (UWB) radars, 77 GHz frequency modulated continuous wave (FMCW) data from millimeter wave (mmWave) radar, visual and audio information, lip landmarks and laser data, offering a unique multimodal approach to speech recognition research. Meanwhile, a depth camera is adopted to record the landmarks of the subject's lip and voice. Approximately 400 minutes of annotated speech profiles are provided, which are collected from 20 participants speaking 5 vowels, 15 words, and 16 sentences. The dataset has been validated and has potential for the investigation of lip reading and multimodal speech recognition.

Competitive Chemical Reaction Kinetic Model of Nucleosome Assembly Using the Histone Variant H2A.Z and H2A In Vitro.

Nucleosomes not only serve as the basic building blocks for eukaryotic chromatin but also regulate many biological processes, such as DNA replication, repair, and recombination. To modulate gene expression in vivo, the histone variant H2A.Z can be dynamically incorporated into the nucleosome. However, the assembly dynamics of H2A.Z-containing nucleosomes remain elusive. Here, we demonstrate that our previous chemical kinetic model for nucleosome assembly can be extended to H2A.Z-containing nucleosome assembly processes. The efficiency of H2A.Z-containing nucleosome assembly, like that of canonical nucleosome assembly, was also positively correlated with the total histone octamer concentration, reaction rate constant, and reaction time. We expanded the kinetic model to represent the competitive dynamics of H2A and H2A.Z in nucleosome assembly, thus providing a novel method through which to assess the competitive ability of histones to assemble nucleosomes. Based on this model, we confirmed that histone H2A has a higher competitive ability to assemble nucleosomes in vitro than histone H2A.Z. Our competitive kinetic model and experimental results also confirmed that in vitro H2A.Z-containing nucleosome assembly is governed by chemical kinetic principles.

Role of hydrogels in osteoarthritis: A comprehensive review.

Osteoarthritis (OA) is a chronic, degenerative, and age-related disease. It is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. The current effective treatment for OA is limited. Hydrogel is a kind of unique carrier with well-known biocompatibility, softness, and high water content among various biomaterials. Hydrogels are developed for different biomedical applications, for instance, drug delivery, and tissue engineering. To date, a variety of hydrogels-based therapies have been used in OA patients or animal models. In this review, we comprehensively summarized the potential role of hydrogels in chondrocytes proliferation, apoptosis, and inflammatory component production and discussed the impact of hydrogels on OA development. The collection of this information will help better understand the present progress of hydrogels in OA.

Effect of Shear History on Solid-Liquid Transition of Particulate Gel Fuels.

Investigating the structural evolution of particulate gels is a very challenging task due to their vulnerability and true flow characteristics. In this work, deeper insight into the rheological properties of gel fuels filled with fumed silica (FS) and aluminum microparticles (Al MPs) was gained by changing shear procedures. Firstly, the flow curves were found to no longer follow the monotonic power law and exhibited subtle thixotropic responses. As the shear rate increased, the gel structure underwent a transition from local shear to bulk shear in the nonlinear region after yielding. This finding reveals the prevalence of nonideal local shear in industry. Secondly, the time-dependent rheological responses demonstrated that the strength spectrum of gel fuels depends on the applied shear rate, with stress relaxation more easily observed at lower shear rates. Those results involved the structural disruption, recovery, and equilibrium of particulate gels from two scales of shear rate and shear time.

How Does Mitochondrial Protein-Coding Gene Expression in Fejervarya kawamurai (Anura: Dicroglossidae) Respond to Extreme Temperatures?

Unusual climates can lead to extreme temperatures. Fejervarya kawamurai, one of the most prevalent anurans in the paddy fields of tropical and subtropical regions in Asia, is sensitive to climate change. The present study focuses primarily on a single question: how do the 13 mitochondrial protein-coding genes (PCGs) respond to extreme temperature change compared with 25 °C controls? Thirty-eight genes including an extra tRNA-Met gene were identified and sequenced from the mitochondrial genome of F. kawamurai. Evolutionary relationships were assessed within the Dicroglossidae and showed that Dicroglossinae is monophyletic and F. kawamurai is a sister group to the clade of (F. multistriata + F. limnocharis). Transcript levels of mitochondrial genes in liver were also evaluated to assess responses to 24 h exposure to low (2 °C and 4 °C) or high (40 °C) temperatures. Under 2 °C, seven genes showed significant changes in liver transcript levels, among which transcript levels of ATP8, ND1, ND2, ND3, ND4, and Cytb increased, respectively, and ND5 decreased. However, exposure to 4 °C for 24 h was very different in that the expressions of ten mitochondrial protein-coding genes, except ND1, ND3, and Cytb, were significantly downregulated. Among them, the transcript level of ND5 was most significantly downregulated, decreasing by 0.28-fold. Exposure to a hot environment at 40 °C for 24 h resulted in a marked difference in transcript responses with strong upregulation of eight genes, ranging from a 1.52-fold increase in ND4L to a 2.18-fold rise in Cytb transcript levels, although COI and ND5 were reduced to 0.56 and 0.67, respectively, compared with the controls. Overall, these results suggest that at 4 °C, F. kawamurai appears to have entered a hypometabolic state of hibernation, whereas its mitochondrial oxidative phosphorylation was affected at both 2 °C and 40 °C. The majority of mitochondrial PCGs exhibited substantial changes at all three temperatures, indicating that frogs such as F. kawamurai that inhabit tropical or subtropical regions are susceptible to ambient temperature changes and can quickly employ compensating adjustments to proteins involved in the mitochondrial electron transport chain.

Uncovering the mechanisms of salicylic acid-mediated abiotic stress tolerance in horticultural crops.

Salicylic acid (SA) has been recognized as a promising molecule for improving abiotic stress tolerance in plants due to its ability to enhance antioxidant defense system, and promote root architecture system. Recent research has focused on uncovering the mechanisms by which SA confers abiotic stress tolerance in horticultural crops. SA has been shown to act as a signaling molecule that triggers various physiological and morphological responses in plants. SA regulates the production of reactive oxygen species (ROS). Moreover, it can also act as signaling molecule that regulate the expression of stress-responsive genes. SA can directly interact with various hormones, proteins and enzymes involved in abiotic stress tolerance. SA regulates the antioxidant enzymes activities that scavenge toxic ROS, thereby reducing oxidative damage in plants. SA can also activate protein kinases that phosphorylate and activate transcription factors involved in stress responses. Understanding these mechanisms is essential for developing effective strategies to improve crop resilience in the face of changing environmental conditions. Current information provides valuable insights for farmers and plant researchers, offering new strategies to enhance crop resilience and productivity in the face of environmental challenges. By harnessing the power of SA and its signaling pathways, farmers can develop more effective stress management techniques and optimize crop performance. Plant researchers can also explore innovative approaches to breed or engineer crops with enhanced stress tolerance, thereby contributing to sustainable agriculture and food security.

Two-Fold ND5 Genes, Three-Fold Control Regions, lncRNA, and the "Missing" ATP8 Found in the Mitogenomes of Polypedates megacephalus (Rhacophridae: Polypedates).

In prior research on the mitochondrial genome (mitogenome) of Polypedates megacephalus, the one copy of ND5 gene was translocated to the control region (CR) and the ATP8 gene was not found. Gene loss is uncommon among vertebrates. However, in this study, we resequenced the mitogenomes of P. megacephalus from different regions using a "primer bridging" approach with Sanger sequencing technologies, which revealed the "missing" ATP8 gene in P. megacephalus as well as three other previously published Polypedates. The mitogenome of this species was found to contain two copies of the ND5 genes and three copies of the control regions. Furthermore, multiple tandem repeats were identified in the control regions. Notably, we observed that there was no correlation between genetic divergence and geographic distance. However, using the mitogenome, gene expression analysis was performed via RT-qPCR of liver samples and it was thus determined that COIII, ND2, ND4, and ND6 were reduced to 0.64 ± 0.24, 0.55 ± 0.34, 0.44 ± 0.21 and 0.65 ± 0.17, respectively, under low-temperature stress (8 °C) as compared with controls (p < 0.05). Remarkably, the transcript of long non-coding RNA (lncRNA) between positions 8029 and 8612 decreased significantly with exposure to low-temperature stress (8 °C). Antisense ND6 gene expression showed a downward trend, but this was not significant. These results reveal that modulations of protein-coding mitochondrial genes and lncRNAs of P. megacephalus play a crucial role in the molecular response to cold stress.

Quantitative evaluation of artifact expression in conebeam computed tomography of mesoporous calcium silicate nanoparticles as a promising root canal sealer.

OBJECTIVES: We aimed to quantitatively compare the area and volume of artifacts in cone beam computed tomography produced by mesoporous calcium silicate nanoparticles (MCSNs), AH Plus sealer, and iRoot SP sealer when used as root canal sealers. METHODS: We prepared 40 single-rooted mandibular premolars and divided them into an MCSN sealer group, an AH Plus sealer group, an iRoot SP sealer group, and a no-sealer (control) group. We filled the canals with gutta-percha using the single-cone method and subjected them to conebeam computed tomography before and after the placement of root fillings using the same exposure parameters. We evaluated the images to quantify the areas of hyperdense and hypodense artifacts and non-affected teeth and reconstructed 3-dimensional image models of the materials to study volume distortion artifacts. RESULTS: The MCSN sealer group produced a significantly smaller hyperdense and volume distortion artifacts than the AH Plus and iRoot SP groups (P < .01), but the area and volume of hypodense artifacts did not differ significantly among the groups (P > .05). CONCLUSIONS: When used as a root canal sealer, MCSNs generate a significantly smaller area and volume of hyperdense artifacts than AH Plus and iRoot SP sealers. By significantly reducing the generation of high-density artifacts, MCSNs may facilitate the evaluation of root canal filling quality and the diagnosis of root canal abnormalities.

Ethylene-induced improvement in photosynthetic performance of Zanthoxylum armatum under reoxygenation conditions.

In this study, we evaluated the photosynthetic performance of Zanthoxylum armatum seedlings to test the tolerance to reoxygenation after waterlogging. The experiment included a control group without waterlogging (NW) and three reoxygenation groups with reoxygenation after 1day (WR1), 2days (WR2) and 3days (WR3). Seedlings were pretreated with concentrations of 0, 200 and 400µmolL-1 of ethylene. The results showed that reoxygenation after waterlogging for 1-3days decreased photosynthetic pigments content, enzymes activity, stomatal conductance (G s ), net photosynthetic rate (P n ), transpiration rate (T r ) and water-use efficiency (WUE). However, pretreatment with ethylene increased photosynthetic pigments content, enzymes activity and gas exchange parameters under both NW and WR3 treatments. The chlorophyll fluorescence results showed that the maximum quantum yield of PSII (F v /F m ) and actual photochemical efficiency of PSII (Φ PSII ) remained no significant changes under the NW and WR1 treatments, while they were significantly reduced with an increase in waterlogging days followed by reoxygenation under WR2 and WR3 treatments. Exogenous ethylene inhibited F v /F m and the non-photochemical quenching coefficient (NPQ), while enhanced Φ PSII and electron transfer efficiency (ETR) under WR2 treatments. Moreover, the accumulation of exogenous ethylene reduced photosynthetic ability. These findings provide insights into the role of ethylene in enhancing the tolerance of Z. armatum to reoxygenation stress, which could help mitigate the impact of continued climate change.

Predictors of Revascularization in Lower-Extremity Peripheral Artery Disease: Insights From the PORTRAIT Study.

BACKGROUND: Peripheral artery disease (PAD) guidelines recommend revascularization only for patients with lifestyle-limiting claudication that is refractory to goal-directed medical therapy (class IIA, level of evidence A). However, real-world invasive treatment patterns and predictors of revascularization in patients with symptomatic lower-extremity PAD are still largely unknown. AIM: We aimed to examine rates, patient-level predictors, and site variability of early revascularization in patients with new or worsening PAD symptoms. METHODS: Among patients with new-onset or recent exacerbation of PAD in the 10-center Patient-centered Outcomes Related to TReatment practices in peripheral Arterial disease: Investigating Trajectories (PORTRAIT) study enrolled between June 2011 and September 2015, we classified early revascularization (endovascular or surgical) as procedures being performed within 3 months of presentation. Hierarchical logistic regression was used to identify patient characteristics associated with early revascularization. Variability across sites was estimated using the median odds ratio (OR). RESULTS: Among 797 participants, early revascularization procedures were performed in 224 (28.1%). Rutherford class 3 (vs Rutherford class 1; OR=1.86, 95% confidence interval [CI] 1.04-3.33) and having lesions in both iliofemoral and below-the-knee arterial segments (vs below the knee only; OR=1.75, 95% CI: 1.15-2.67) were associated with a higher odds of revascularization. Longer PAD duration >12 months (vs 1-6 months; OR=0.50, 95% CI: 0.32-0.77), higher ankle-brachial index scores (per 0.1 unit increase; OR=0.86, 95% CI: 0.78-0.96), and higher Peripheral Artery Questionnaire Summary scores (per 10 unit increase; OR=0.89, 95% CI: 0.80-0.99) were associated with a lower odds of revascularization. The raw rates for revascularization in different sites ranged from 6.25% to 66.28%, and the median OR was 1.88, 95% CI: 1.38-3.57. CONCLUSIONS: About 1 in 3 patients with symptomatic PAD received early revascularization. A more extensive disease and symptom burden were the main predictors of receiving early revascularization in PAD. There was significant site variability in revascularization patterns, and further studies will better understand the source of this variability and optimal selection criteria for early revascularization. CLINICAL IMPACT: Real world patterns and predictors of early revascularization in peripheral artery disease are not well understood. In this retrospective analysis of the POTRAIT study, about 1 out of 3 patients with PAD symptoms received early revascularization, with significant site variability. A more extensive disease and symptom burden were the main predictors of receiving early revascularization in PAD.