Search Results (1,168)

Background: High-sensitivity cardiac troponin (hs-cTn) is useful for detecting acute myocardial infarction, but chronic hemodialysis patients often have elevated baseline levels that exceed the upper reference limit (URL). This study aimed to determine whether hs-cTnI levels in asymptomatic hemodialysis patients exceed the URL established for the general population, evaluate the impact of high-flux hemodialysis on hs-cTnI concentrations, and examine associations between hs-cTnI levels and subsequent hospitalization or mortality. Methods: A prospective, single-center cohort study was conducted at a tertiary care center from August 2023 to July 2024. Blood samples for hs-cTnI were collected from asymptomatic hemodialysis patients aged ≥ 40 years, measured before and after dialysis within one month. Patients were followed for up to 12 months. Results: Fifty-six patients were enrolled. The mean hs-cTnI levels were 28.4 ng/L pre-dialysis and 27.9 ng/L post-dialysis, with ranges of <6–223 ng/L and <6–187 ng/L, respectively. The mean hs-cTnI delta between pre- and post-dialysis was −0.5 ng/L, with 52% showing a negative delta, 30% no change, and 18% a positive delta. No association was found between baseline hs-cTnI levels and mortality or hospitalization during follow-up. Conclusions: Most asymptomatic hemodialysis patients had hs-cTnI levels in the “gray zone”, thus neither confirming nor excluding acute myocardial infarction. Dialysis did not significantly affect hs-cTnI levels, and elevated baseline hs-cTnI was not linked to increased mortality or hospitalization over 12 months. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

Eco-enzymatic stoichiometry provides a basis for understanding soil ecosystem functions, with implications for land management and ecological protection. Long-term climatic factors and human interferences have caused significant land-use transformations in the Qinghai–Tibet Plateau region, affecting various ecological functions, such as soil nutrient cycling and chemical element balance. It is currently unclear how large-scale land-use conversion affects soil ecological stoichiometry. In this study, 763 soil samples were collected across three land-use types: farmland, grassland, and forest land. In addition, changes in soil physicochemical properties and enzyme activity and stoichiometry were determined. The soil available phosphorus (SAP) and total phosphorus (TP) concentrations were the highest in farmland soil. Bulk density, pH, SAP, TP, and NO₃⁻-N were lower in forest soil, whereas NH₄⁺-N, available nitrogen, soil organic carbon (SOC), available potassium, and the soil nutrient ratio increased. Land-use conversion promoted soil β-1,4-glucosidase, N-acetyl-β-glucosaminidase, and alkaline phosphatase activities, mostly in forest soil. The eco-enzymatic C:N ratio was higher in farmland soils but grassland soils had a higher enzymatic C:P and N:P. Soil microorganisms were limited by P nutrients in all land-use patterns. C limitation was the highest in farmland soil. The redundancy analysis indicated that the ecological stoichiometry in farmland was influenced by TN, whereas grass and forest soils were influenced by SOC. Overall, the conversion of cropland or grassland to complex land-use types can effectively enhance soil nutrients, enzyme activities, and ecosystem functions, providing valuable insights for ecological restoration and sustainable land management in alpine regions. Full article

Background/Objectives: Doxorubicin is a chemotherapeutic agent whose clinical use is limited by side effects (SEs). The most common SE is doxorubicin-induced cardiotoxicity (DIC), for which there is still no prevention. The hypothesis arises that active substances of natural origin could influence DIC prevention by affecting several pathways of DIC occurrence. Methods: Thirty Wistar rats were divided into six groups (control, NADES (C8:C10) solvent, pumpkin pulp extract, doxorubicin, NADES (C8:C10) solvent–doxorubicin, and pumpkin pulp extract–doxorubicin). During the experiment, parameters of general condition, body, and heart weight were observed. Heart function parameters were monitored by measuring the levels of serum NT-pro-BNP, CK-MB, and hsTnT. Tissue damage was evaluated by determining the doxorubicin damage score and the expression of anti-cardiac troponin I, anti-Nrf2, anti-Bcl-2, anti-caspase-3, anti-COX2, and anti-Ki67 antibodies. Results: Doxorubicin administration led to impaired general condition of animals and increased the levels of NT-proBNP, CK-MB, hsTnT, and myocardium tissue damage of medium grade. Its administration induced apoptosis (as evidenced by elevated Casp3), reduced antiapoptotic Bcl-2 and troponin I expression in cardiomyocytes. Reduced Nrf2 expression due to doxorubicin administration was restored when pumpkin pulp extract containing carotenoids was coadministered, which led to the normalization of Casp3, Bcl-2, and troponin I expression. Consequently, the general condition and body weight were better in animals treated with both doxorubicin and the other treatment compared to those treated with doxorubicin alone. Conclusions: The results of this study strongly suggest that pumpkin pulp extract containing carotenoids has a cardioprotective effect, possibly by regulating the Nrf2 pathway. Full article

Tetranectin (TN) is a plasminogen-binding protein found in human serum. Although it has been suggested to be closely related to various stem cell differentiation, including myogenesis, the role of TN in muscle development remains unclear. In this study, we identified TN as an anti-myogenic factor during the differentiation of C2C12 satellite cells. The exogenous supplementation of TN inhibited myogenic differentiation, whereas differentiation was significantly enhanced in the TN-depleted medium. Epigallocatechin-3-gallate (EGCG), a catechin abundant in green tea, significantly enhanced myogenic differentiation by reducing TN levels in the medium and downregulating TN gene expression during the differentiation process. These results demonstrate that EGCG promotes myogenesis by inhibiting TN at both the transcriptional and functional levels, highlighting TN as a promising therapeutic target for muscle regeneration disorders. Full article

This study aims to analyze the differences in soil bacterial community structure under different vegetation restoration types, and to explore the role of microorganisms in the process of vegetation restoration on the soil ecosystem of the Grain for Green area in the Loess Plateau. High-throughput sequencing technology was used to analyze the alpha diversity of soil bacteria, community structure characteristics, and the correlation between soil environmental factors and bacterial communities in different artificial Hippophae rhamnoides forests. Soil microbial C and N show a decreasing trend with an increase in the 0–100 cm soil layers. The results indicated that the bacterial communities comprised 24 phyla, 55 classes, 110 orders, 206 families, 348 genera, 680 species, and 1989 OTUs. Additionally, the richness indices and diversity indices of the bacterial community in arbor shrub mixed forest are higher than those in shrub pure forest, and the indices of shrub forest on sunny slope are higher than those on shady slope. Across all samples, the dominant groups were Actinobacteria (37.27% on average), followed by Proteobacteria (23.91%), Acidobacteria (12.75%), and Chloroflexi (12.27%). Soil nutrient supply, such as TOC, TN, AN, AP, and AK, had crucial roles in shaping the composition and diversity of the bacterial communities. The findings reveal that vegetation restoration significantly affected soil bacterial community richness and diversity. Furthermore, based on the results, our data provide a starting point for establishing soil bacterial databases in the Loess Plateau, as well as for the plants associated with the vegetation restoration. Full article

Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article

A novel cellulose-degrading bacterial strain, D3-1, capable of degrading cellulose under medium- to high-temperature conditions, was isolated from soil samples and identified as Staphylococcus caprae through 16SrRNA gene sequencing. The strain’s cellulase production was optimized by controlling different factors, such as pH, temperature, incubation period, substrate concentration, nitrogen and carbon sources, and response surface methods. The results indicated that the optimal conditions for maximum cellulase activity were an incubation time of 91.7 h, a temperature of 41.8 °C, and a pH of 4.9, which resulted in a maximum cellulase activity of 16.67 U/mL, representing a 165% increase compared to pre-optimization levels. The above experiment showed that, when maize straw flour was utilized as a natural carbon source, strain D3-1 exhibited relatively high cellulase production. Furthermore, gas chromatography–mass spectrometry (GC-MS) analysis of products in the degradation liquid revealed the presence of primary sugars. The results indicated that, in the denitrification of simulated sewage, supplying maize straw flour degradation liquid (MSFDL) as the carbon source resulted in a carbon/nitrogen (C/N) ratio of 6:1 after a 24 h reaction with the denitrifying strain WH-01. The total nitrogen (TN) reduction was approximately 70 mg/L, which is equivalent to the removal efficiency observed in the glucose-fed denitrification process. Meanwhile, during a 4 h denitrification reaction in urban sewage without any denitrifying bacteria, but with MSFDL supplied as the carbon source, the TN removal efficiency reached 11 mg/L, which is approximately 70% of the efficiency of the glucose-fed denitrification process. Furthermore, experimental results revealed that strain D3-1 exhibits some capacity for nitrogen removal; when the cellulose-degrading strain D3-1 is combined with the denitrifying strain WH-01, the resulting TN removal rate surpasses that of a single denitrifying bacterium. In conclusion, as a carbon source in municipal sewage treatment, the degraded maize straw flour produced by strain D3-1 holds potential as a substitute for the glucose carbon source, and strain D3-1 has a synergistic effect with the denitrifying strain WH-01 on TN elimination. Thus, this research offers new insights and directions for advancement in environmental sewage treatment. Full article

Elevational gradients in temperature, moisture, and vegetation strongly influence soil nutrient content and stoichiometry in mountainous regions. However, exactly how total, microbial, and enzymatic carbon (C), nitrogen (N), and phosphorus (P) stoichiometry vary with elevation in karst peak-cluster depressions remains poorly understood. To address this, we studied soil total, microbial, and enzymatic C:N:P stoichiometry in seasonal rainforests within karst peak-cluster depressions in southwestern China at different elevations (200, 300, 400, and 500 m asl) and depths (0–20 and 20–40 cm). We found that soil organic carbon (SOC), total nitrogen (TN), and the C:P and N:P ratios increased significantly with elevation, whereas total phosphorus (TP) decreased. Microbial phosphorus (MBP) also declined with elevation, while the microbial N:P ratio rose. Activities of nitrogen- (β-N-acetylglucosaminidase and L-leucine aminopeptidase combined) and phosphorus-related enzymes (alkaline phosphatase) increased markedly with elevation, suggesting potential phosphorus limitation for plant growth at higher elevations. Our results suggest that total, microbial, and enzymatic soil stoichiometry are collectively shaped by topography and soil physicochemical properties, with elevation, pH, and exchangeable calcium (ECa) acting as the key drivers. Microbial stoichiometry exhibited positive interactions with soil stoichiometry, while enzymatic stoichiometry did not fully conform to the expectations of resource allocation theory, likely due to the functional specificity of phosphatase. Overall, these findings enhance our understanding of C–N–P biogeochemical coupling in karst ecosystems, highlight potential nutrient limitations, and provide a scientific basis for sustainable forest management in tropical karst regions. Full article

Background/Objectives: Elevated troponin levels are widely recognized as key biomarkers of myocardial injury and are frequently used in clinical decision making. However, not all instances of troponin elevation indicate true cardiac damage. In some cases, biochemical or immunological interferences may lead to false-positive results. These situations may lead to unnecessary diagnostic interventions and clinical uncertainty, ultimately impacting patient management negatively. This study aims to investigate the underlying mechanisms of false-positive troponin elevation in pediatric patients, focusing on factors such as macrotroponin formation, autoantibodies, and heterophile antibody interference. Methods: This retrospective study analyzed data from 13 pediatric patients who presented with elevated cardiac troponin levels between 2017 and 2024. Clinical evaluations included transthoracic echocardiography (TTE), electrocardiography (ECG), coronary computed tomography angiography (CTA), cardiac magnetic resonance imaging (MRI), and rheumatologic testing. Laboratory findings included measurements of cardiac troponins (cTnI and hs-cTnT) and pro-BNP levels. Results: Among 70 patients evaluated for elevated troponin levels, 13 (18.6%) were determined to have no identifiable cardiac etiology. The median age of these 13 patients was 13.0 years (range: 9–16), with 53.8% being female. The most common presenting complaints were chest pain (53.8%) and palpitations (30.8%). TTE findings were normal in 61.5% of the patients, and all patients had normal coronary CTA and cardiac MRI findings. Although initial troponin I levels were elevated in all cases, persistent positivity was observed up to 12 months. Median cTnI levels were 1.00 ng/mL (range: 0.33–7.19) at week 1 and 0.731 ng/mL (range: 0.175–4.56) at month 12. PEG precipitation testing identified macrotroponin in three patients (23.1%). No etiological explanation could be identified in 10 cases (76.9%), which were considered idiopathic. All patients had negative results for heterophile antibody and rheumatologic tests. Conclusions: When interpreting elevated troponin levels in children, biochemical interferences—especially macrotroponin—should not be overlooked. This study emphasizes the diagnostic uncertainty associated with non-cardiac troponin elevation. To better guide clinical practice and clarify false positivity rates, larger, multicenter prospective studies are needed. Full article

Background: We evaluated the Sysmex Highly Integrated Single-Cartridge Luminescence Immunoassay System (HISCL) hs-cTnT assay, and compared its performance to the Roche assay, with derivation of 99th-percentile upper reference limits (99% URLs) for healthy subjects. We assessed the effect of increasing age/decreasing eGFR on the HISCL hs-cTnT. Methods: We verified assay limits of blank/detection, precision and the functional sensitivity. Samples were analyzed on both the Sysmex HISCL and Roche Elecsys analyzers for method comparison. Results: The HISCL assay limit of blank/detection was 1.3/1.9 ng/L, and concentrations corresponding to 20/10% CVs were 1.8/3.3 ng/L. Assay precision of kit controls at 3253 ng/L was 2.2% and at 106 ng/L was 2.5%. Linear regression analysis (n = 2151) showed good agreement (r = 0.95) with the Roche hs-cTnT. Bland–Altman (Roche/HISCL) analysis for samples with hs-cTnT ≤ 52 ng/L showed a mean absolute difference of 3.5 ng/L; for hs-cTnT > 52 ng/L, the mean difference was 2.8%. In a cardio-renal healthy population (n = 1004), the 99% URLs were 14.4/17.0/13.9 ng/L for overall/male/female, respectively; assay CV% was below 10% at these levels. More than 50% of the hs-cTnT in the healthy male and female subjects were measurable above the limit of detection. Hs-cTnT increased with increasing age and decreasing eGFR. Conclusions: In conclusion, the Sysmex HISCL hs-cTnT fulfils the criteria for a high-sensitivity assay, with specific 99th URLs for males and females. Expectedly, the baseline Sysmex hs-cTnT increases with age and decreasing eGFR. Full article

Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice for Tsn (TN) or Tsnax (TX) using DAT-Cre. Immunostaining confirmed efficient TX loss in Tsnax cKO DA neurons without affecting TN, while Tsn deletion abolished TX expression, revealing asymmetric protein dependency. Body composition analysis showed no alterations in adiposity in either cKO model. Locomotor responses to acute or repeated administration of cocaine (20 mg/kg) or amphetamine (2.5 mg/kg) were unchanged in Tsn or Tsnax cKO mice. Furthermore, amphetamine-induced conditioned place preference (1 mg/kg) was unaffected. These results demonstrate that the TN/TX complex within DA neurons is dispensable for regulating adiposity, psychostimulant-induced locomotion (both acute and sensitized), or amphetamine reward-related behavior, suggesting its critical functions may lie outside these specific domains. Full article

Background: Coronavirus disease 2019 (COVID-19) is frequently complicated by cardiovascular involvement. Soluble growth stimulation-expressed gene 2 (sST2) is a promising cardiovascular biomarker, but its prognostic value in COVID-19 remains unclear. Methods: This retrospective cohort study included 314 hospitalized COVID-19 patients classified into mild/moderate (n = 168) and severe/critical (n = 146). Plasma sST2 were measured using an enzyme-linked immunosorbent assay. Correlation analyses evaluated associations between sST2 and clinical parameters. Cox regression assessed the independent predictive value for cardiovascular events and all-cause mortality. Results: sST2 levels were significantly higher in severe/critical patients (16.877 ng/mL) than in mild/moderate cases (6.189 ng/mL) and healthy controls (4.003 ng/mL). sST2 positively correlated with cardiac injury markers (cTnI, CK-Mb, NT-proBNP), inflammatory indices (IL-1β, hsCRP), D-dimer, and inversely correlated with a left ventricular ejection fraction (r = −0.86). Elevated sST2 independently predicted cardiovascular events (HR = 2.972) and mortality (HR = 4.681). The Kaplan–Meier survival analysis demonstrated higher cardiovascular event rates and lower survival probabilities in patients with elevated sST2. The ROC curve indicated sST2 outperformed cTnI and NT-proBNP in predicting cardiovascular events (AUC = 0.898) and mortality (AUC = 0.871). Conclusion: Elevated sST2 is associated with myocardial injury, inflammation, and poor prognosis in COVID-19, supporting its value for risk stratification. Full article

Urban forests provide essential ecosystem services, including improving soil health, sequestering carbon (C), and supporting biodiversity. However, the effects of anthropogenic litter and root management on soil biogeochemical processes in urban environments remain poorly understood. This study applied the Detritus Inputs and Removal Treatment (DIRT) framework to examine how aboveground and belowground organic inputs influence soil organic carbon (SOC), total nitrogen (TN), soil water content (SWC), and enzymatic activities in subtropical urban camphor tree forests in China. Six treatments were implemented: litter removal (LR), litter addition (LA), root exclusion (RE), combined litter and root removal (LR + RE), combined litter addition and root exclusion (LA + RE), and an undisturbed litter control (LC). The results showed that the LA treatment significantly enhanced SOC, TN, SWC, and key soil enzyme activities (protease, catalase, and urease) compared to the LC, highlighting the crucial role of litter in enhancing soil fertility and microbial functioning. These elevated enzyme activities suggest intensified microbial nutrient cycling and metabolic activity in response to organic matter inputs. In contrast, the combined LR + RE treatment reduced SOC and enzyme activities but unexpectedly increased TN, indicating disrupted nutrient cycling, possibly due to accelerated microbial nitrogen mineralization and decomposition of existing soil organic matter in the absence of fresh carbon inputs. The LA treatment also showed the highest carbon-to-nitrogen (C:N) ratio, reflecting a carbon-enriched environment that may favor long-term carbon stabilization. Additionally, SWC was most improved under the LA + RE treatment, suggesting its potential for enhancing soil moisture retention in urban settings. These findings underscore the complementary roles of litter and root inputs in maintaining soil health and biogeochemical balance in urban forests. The study provides insights into enzyme-mediated soil processes under varying organic input regimes and highlights the value of targeted organic matter management to enhance urban ecosystem services. Full article

Background: Polysubstance use, particularly combining opioids with stimulants such as cocaine, is rising among individuals with substance use disorders. This practice aims to balance cocaine’s stimulant effects with opioids’ sedative effect, potentially decreasing adverse outcomes. We hypothesized that concurrent exposure to cocaine and opioids would reduce the risk of neonatal opioid withdrawal syndrome (NOWS) compared to opioid use alone. Methods: This analysis draws from an ongoing prospective study of maternal substance use (SUD) at Regional One Health’s perinatal center in Memphis, TN, and included mothers and their infants born between 2018 and 2022. Maternal SUD was identified via screening questionnaires, urine toxicology, or umbilical cord tissue analysis. Participants were grouped into using (a) opioids with cocaine (OwC) and (b) opioids without cocaine (OwoC). Univariate and regression analyses were conducted to assess the risk of NOWS. Results: A total of 353 infants were born to 342 mothers, with 31% (110/353) of the infants born to women who used cocaine along with opioids. While maternal demographics were similar, the OwC group had significantly lower rates of prenatal care, chronic pain history, and MOUD enrollment (p = 0.03). Infants in the OwC group had significantly higher rates of NOWS (p < 0.01), longer hospital stays (p < 0.01), and 6.5 times greater odds of developing NOWS (p < 0.001). NOWS was associated with an average 15-day increase in the length of stay for term infants (95% CI: 11.2, 18.8; p < 0.001). Conclusions: Contrary to our hypothesis, our study highlights the significant impact of maternal cocaine use on the increased likelihood of NOWS and extended hospital stays for affected infants. Full article