Search Results (14,302)

Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies. Full article

This research explored the effects of different concentrations of p-coumaric acid (PCA) on the quality of frozen-thawed boar semen. Boar sperm samples were pre-treated with different concentrations of PCA (0, 30, 60, 90, 120 μg/mL) prior to the freezing process. Subsequently, multiple parameters were analyzed post-freeze-thawing, including sperm morphological and kinetic characteristics, acrosome and membrane integrity, mitochondrial function, DNA integrity, antioxidant enzyme activities, the expression levels of the BCL-2, BAX, and Caspase-3 proteins, the in vitro fertilization rate of porcine oocytes, and the embryo cleavage rate. The findings indicated that, compared with the control group, the addition of 90 μg/mL PCA led to significant improvements in several key aspects. Sperm motility, average path velocity, straight-line velocity, curvilinear velocity, and beat cross frequency were all notably enhanced. Moreover, parameters related to sperm quality, such as acrosome integrity, plasma membrane integrity, mitochondrial activity, and DNA integrity, also showed significant increases (all p < 0.05). In terms of antioxidant capacity, the 90 μg/mL PCA treatment significantly elevated the total antioxidant capacity, as well as the activities of superoxide dismutase, glutathione peroxidase, and catalase. Simultaneously, it caused a significant reduction in the contents of malondialdehyde and hydrogen peroxide (p < 0.05). Regarding protein expression, the addition of 90 μg/mL PCA significantly upregulated the expression level of the BCL-2 protein, while downregulating the relative expression levels of BAX and Caspase-3 (p < 0.05). Additionally, this concentration of PCA significantly improved the in vitro fertilization rate of porcine oocytes and the embryo cleavage rate (p < 0.05). In conclusion, incorporating PCA into the semen extender can potentially be advantageous for the cryopreservation of boar sperm, with 90 μg/mL being the optimal concentration. Full article

Applied muscular strain and hamstring strain capacity have a joint interaction on hamstring strain injury (HSI) with modifiable risk factors frequently assessed. However, to date there is limited observations on the interaction between these factors. The purpose of the present study was to observe if spatiotemporal characteristics, running kinematics and muscle activation were related to modifiable risk factors of HSI. Twenty-two competitive team sport athletes (24.7 ± 4.3 years, 1.82 ± 0.07 m, 84.9 ± 8.5 kg) participated whereby the Bicep femoris long head (BF_LH) fascicle length assessed via ultrasound and isokinetic eccentric hamstring strength was assessed. With running assessment performed at 18 km/h, capturing running kinematics and muscle activation. Multiple linear regressions were used to examine the relationship of running kinematics and muscle activation on the modifiable risk factors of HSI on. The overall model (F_2,19) was statistically significant for both relative eccentric hamstring strength (F = 23.58, p < 0.001) and BF_LH fascicle length (F = 18.87, p < 0.001) highlighting spatiotemporal characteristics, running kinematics and hamstring activation were found to be significantly related to the modifiable risk factors. There is a complex interrelationship between running mechanics and hamstring muscle properties, with the potential of either cause or consequence association. Full article

Fly ash is a commonly used mineral addition in construction engineering. Research on its different particle size distributions can help optimize material performance, promote resource utilization, and support environmental protection. In this study, the particle size of fly ash was used as a variable; fly ash with a single particle size was prepared by means of sieving, and the particle size was precisely controlled as a variable, thus avoiding the errors caused by the addition of multiple different particle sizes. Replacing 10% of the cement with fly ash to prepare cement mortar, the influence of fly ash particle size on the performance of cement mortar was investigated. The results show that the mortar incorporating fly ash with a particle size range of 10–20 μm achieves a 28-day compressive strength of 58.25 MPa and a flexural strength of 10.29 MPa. The hydration heat release rate of fly ash in the 10–20 μm range reaches a maximum of 1.84 mW/g, and the total hydration heat release peaks at 211.17 J/g at 70 h. The influence of fly ash particle size on the total hydration heat release is relatively small in the early stages but increases rapidly with prolonged hydration time. When the fly ash particle size is in the 10–20 μm range, the cement mortar exhibits the lowest total porosity at 12.88%, with the smallest average pore size of 27.1 nm and the smallest most probable pore size of 21.2 nm. This reduces harmful pores, increases the number of harmless pores, makes the cement mortar structure denser, and improves the durability of the mortar. The types of hydration products of different particle sizes of fly ash did not change. The smaller the particle size of fly ash, the more complete the volcanic ash reaction, promoting the hydration of mortar. Full article

Background and Objectives: Acute pulmonary thromboembolism (PTE) is one of the leading causes of cardiovascular mortality. Recent insights into PTE pathophysiology emphasize the complex interplay of multiple mechanisms, particularly the roles of thrombosis and inflammation. Methods: This retrospective, single-center observational study included 138 participants: 69 adult patients diagnosed with PTE via computed tomography pulmonary angiography (CTPA) and 69 matched healthy controls. Upon admission, a standard 12-lead electrocardiogram (ECG) was performed, and Daniel’s score was calculated. Peripheral blood samples were collected to assess inflammatory biomarkers and hemogram-derived ratios (SII, NLR, dNLR, NPR, PLR, LMR). CTPA scans were analyzed not only for diagnostic purposes and PTE localization but also for inflammatory changes. PTE severity was classified according to the 2019 ESC guidelines. Results: Patients with PTE had significantly higher Daniel’s ECG scores, initial values of inflammatory biomarkers (WBC, neutrophils, IL-6, CRP) and hemogram-derived ratios (SII, NLR, dNLR, NPR) compared to controls. In multivariate analysis, older age (OR = 1.05; p = 0.038), higher Daniel’s ECG score (OR = 1.24; p < 0.001), and higher dNLR (OR = 1.40; p = 0.001) were found as an independent predictors of PTE severity. Ground-glass opacity (GGO) was the most common parenchymal and pleural inflammatory finding relating to CTPA (48.4%), but these findings did not show significant predictive value for PTE severity. Conclusions: Daniel’s ECG score and dNLR, both readily available and cost-effective biomarkers demonstrated independent predictive value for assessing PTE severity. Full article

The filarioid nematode Dirofilaria immitis is the causative agent of heartworm disease, a major parasitic infection of canids, felids and occasionally humans. Current prevention relies on macrocyclic lactone-based chemoprophylaxis, but the emergence of drug resistance highlights the need for new intervention strategies. Here, we applied a machine learning (ML)-based framework to predict and prioritise essential genes in D. immitis in silico, using genomic, transcriptomic and functional datasets from the model organisms Caenorhabditis elegans and Drosophila melanogaster. With a curated set of 26 predictive features, we trained and evaluated multiple ML models and, using a defined threshold, we predicted 406 ‘high-priority’ essential genes. These genes showed strong transcriptional activity across developmental stages and were inferred to be enriched in pathways related to ribosome biogenesis, translation, RNA processing and signalling, underscoring their potential as anthelmintic targets. Transcriptomic analyses suggested that these genes are associated with key reproductive and neural tissues, while chromosomal mapping revealed a relatively even genomic distribution, in contrast to patterns observed in C. elegans and Dr. melanogaster. In addition, initial evidence suggested structural variation in the X chromosome compared with a recently published D. immitis assembly, indicating the importance of integrating long-read sequencing with high-throughput chromosome conformation capture (Hi-C) mapping. Overall, this study reinforces the potential of ML-guided approaches for essential gene discovery in parasitic nematodes and provides a foundation for downstream validation and therapeutic target development. Full article

Background: Cardiovascular disease (CVD) is the leading global cause of death and is shaped by interacting biological, environmental, lifestyle, and social factors. Traditional models often treat risk factors in isolation and may miss dependencies among exposures and biomarkers. Objective: To map interdependencies among environmental, social, behavioral, and biological predictors of CVD risk using Bayesian network models. Methods: A cross-sectional analysis was conducted using NHANES 2017–2018 data. After complete-case procedures, the analytic sample included 601 adults and 22 variables: outcomes (systolic/diastolic blood pressure, total/LDL/HDL cholesterol, triglycerides) and predictors (BMI, C-reactive protein (CRP), allostatic load, Dietary Inflammatory Index, income, education, age, gender, race, smoking, alcohol, and serum lead, cadmium, mercury, and PFOA). Spearman’s correlations summarized pairwise associations. Bayesian networks were learned with two approaches: Grow–Shrink (constraint-based) and Hill-Climbing (score-based, Bayesian Gaussian equivalent score). Network size metrics included number of nodes, directed edges, average neighborhood size, and Markov blanket size. Results: Correlation screening reproduced expected patterns, including very high systolic–diastolic concordance (p ≈ 1.00), strong LDL–total cholesterol correlation (p = 0.90), inverse HDL–triglycerides association, and positive BMI–CRP association. The final Hill-Climbing network contained 22 nodes and 44 directed edges, with an average neighborhood size of ~4 and an average Markov blanket size of ~6.1, indicating multiple indirect dependencies. Across both learning algorithms, BMI, CRP, and allostatic load emerged as central nodes. Environmental toxicants (lead, cadmium, mercury, PFOS, PFOA) showed connections to sociodemographic variables (income, education, race) and to inflammatory and lipid markers, suggesting patterned exposure linked to socioeconomic position. Diet and stress measures were positioned upstream of blood pressure and triglycerides in the score-based model, consistent with stress-inflammation–metabolic pathways. Agreement across algorithms on key hubs (BMI, CRP, allostatic load) supported network robustness for central structures. Conclusions: Bayesian network modeling identified interconnected pathways linking obesity, systemic inflammation, chronic stress, and environmental toxicant burden with cardiovascular risk indicators. Findings are consistent with the view that biological dysregulation is linked with CVD and environmental or social stresses. Full article

Accurate estimation of the forest canopy height is crucial in monitoring the global carbon cycle and evaluating progress toward carbon neutrality goals. The Global Ecosystem Dynamics Investigation (GEDI) mission provides an important data source for canopy height estimation at a global scale. However, the non-zero half-width of the transmitted laser pulses (NHWTLP) and the influence of terrain slope can cause waveform broadening and overlap between canopy returns and ground returns in GEDI waveforms, thereby reducing the estimation accuracy. To address these limitations, we propose a canopy height retrieval method that combines the deconvolution of GEDI’s transmitted waveforms with terrain slope constraints on the ground response function. The method consists of two main components. The first is performing deconvolution on GEDI’s effective return waveforms using their corresponding transmitted waveforms to obtain the true ground response function within each GEDI footprint, thereby mitigating waveform broadening and overlap induced by NHWTLP. This process includes constructing a convolution convergence function for GEDI waveforms, denoising GEDI waveform data, transforming one-dimensional ground response functions into two dimensions, and applying amplitude difference regularization between the convolved and observed waveforms. The second is incorporating terrain slope parameters derived from a digital terrain model (DTM) as constraints in the canopy height estimation model to alleviate waveform broadening and overlap in ground response functions caused by topographic effects. The proposed approach enhances the precision of forest canopy height estimation from GEDI data, particularly in areas with complex terrain. The results demonstrate that, under various conditions—including GEDI full-power beams and coverage beams, different terrain slopes, varying canopy closures, and multiple study areas—the retrieved height (rh) model constructed from ground response functions derived via the inverse deconvolution of the transmitted waveforms (IDTW) outperforms the RH (the official height from GEDI L2A) model constructed using RH parameters from GEDI L2A data files in forest canopy height estimation. Specifically, without incorporating terrain slope, the rh model for canopy height estimation using full-power beams achieved a coefficient of determination (R²) of 0.58 and a root mean square error (RMSE) of 5.23 m, compared to the RH model, which had an R² of 0.58 and an RMSE of 5.54 m. After incorporating terrain slope, the rh_g model for full-power beams in canopy height estimation yielded an R² of 0.61 and an RMSE of 5.21 m, while the RH_g model attained an R² of 0.60 and an RMSE of 5.45 m. These findings indicate that the proposed method effectively mitigates waveform broadening and overlap in GEDI waveforms, thereby enhancing the precision of forest canopy height estimation, particularly in areas with complex terrain. This approach provides robust technical support for global-scale forest resource assessment and contributes to the accurate monitoring of carbon dynamics. Full article

Sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to infection, and is considered a medical emergency. Therefore, quick diagnosis and treatment are required in order to improve survivability. Currently, patient evaluation in sepsis is based on the Sequential Organ Failure Assessment (SOFA) score to determine the severity of the disease; however, novel biomarkers are also actively researched with the aim to develop quicker diagnostic tools and better therapy. Endothelin-1 is one of the most potent vasoconstrictors found in the human body and is involved in the pathophysiology of both sepsis and other conditions involving organs that make up the SOFA score. In this narrative review, we aimed to gather information of this peptide’s multiple effects and to help determine whether or not it could prove a valuable biomarker in the evaluation of patients with multi-organ dysfunction in sepsis. Full article

The inactivation of thrombin by antithrombin is highly enhanced by the presence of heparin chains forming “bridges” between the two proteins. X-ray structures for such ternary complexes have been published, but the molecular background of the lower efficiency of smaller heparinoids on thrombin inhibition remains poorly understood. Antithrombin-resistant prothrombin mutants (mutations affecting Arg596 in prothrombin) have been reported that cause severe thrombophilia. Our aim was to study the interactions in the antithrombin–thrombin Michaelis complex both in the presence and the absence of a heparinoid chain and in the presence of pentasaccharide by using molecular dynamics. We also intended to study the complexes of thrombin mutants as well as a known alternative antithrombin conformation at the “hinge” region built using docking. The binding between the proteins was investigated by Gaussian Accelerated Molecular Dynamics (GaMD). We compared the contribution of several amino acids at the binding “exosites” between AT and the wild type and mutant thrombins and between systems containing or not containing a heparinoid. In the docking-based simulations, several of the analyzed amino acid pairs no longer contributed to the interaction, suggesting that the open “hinge” conformation has limited biological relevance. We could identify multiple conformational types using clustering, revealing high flexibility in mutants and systems without heparinoid, probably indicating lower stability. We were also able to detect the allosteric effects of the ligands on the bound thrombin. In summary, we were able to obtain conformations using GaMD that can explain the better protein–protein interactions in the ternary complexes and the impaired AT binding of the thrombin Arg596 mutants at an atomic level. Full article

Introduction: While low back pain (LBP) is most often associated with musculoskeletal issues, in a minority of cases, it can be caused by serious underlying conditions such as cancer. Recognizing malignancy early remains a major clinical challenge, as the warning signs, known as red flags (RFs), are often vague and inconsistent. Methods: A comprehensive search of six databases (PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, and SciELO) and grey literature was conducted for studies published from January 1999 to March 2025. Eligible sources included studies describing adult patients with cancer presenting with LBP. Study selection and data extraction were independently performed by two reviewers. Results: We included 70 studies, most of which were case-based, along with reviews and observational research. In these studies, cancer prevalence among patients with LBP ranged from 0.1% to 1.6%, with metastatic disease being the most common finding. A prior history of cancer emerged as the most reliable red flag (specificity up to 0.99), while other signs and symptoms were less consistent. Notably, combining multiple RFs, such as a history of cancer and unexplained weight loss, significantly improved the diagnostic accuracy (LR+ = 10.25 in one study). Conclusions: While current evidence is limited and largely based on case-based studies, some RFs, particularly a history of cancer, show greater diagnostic value. In patients with LBP associated with underlying malignancy, RFs seem to be more useful for ruling in rather than ruling out (i.e., screening) serious pathologies. Most RFs have poor standalone accuracy; however, considering combinations of RFs within the broader clinical context may improve early detection of spinal malignancy in patients with LBP. Full article

The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in regulating immune homeostasis, inflammatory responses, and intestinal barrier function. Indole compounds and their derivatives are ligands of AHR, which can activate the AHR signal transduction pathway and show significant regulatory potential in various inflammatory and immune diseases. Cystic fibrosis (CF) is a life-threatening autosomal recessive genetic disorder. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects multiple systems throughout the body. The core of its pathological process is chronic infection, abnormal inflammation, and tissue damage caused by mucus accumulation. Exploring alternative or adjunctive therapeutic strategies targeting pathological pathways downstream of CFTR is of significant importance. The aim of the present study is to explore the multiple beneficial effects that indole compounds may exert in regulating pulmonary infection and inflammation, repairing intestinal barrier function, and regulating immune homeostasis in CF patients by activating the AHR signaling pathway. Additionally, this study discusses the risks and challenges associated with developing indole compounds as CF drugs, offering a novel research approach distinct from traditional CFTR modulators for creating new CF therapeutics. Full article

Immunotherapy and RAF-targeted therapy have become standard treatments for melanoma, significantly improving outcomes compared to earlier therapies. When resistance to initial treatment develops, the older chemotherapy drug Dacarbazine is used. However, resistance to both therapies has emerged, promoting ongoing research to further enhance survival rates. Among various theories, autophagy is believed to play a critical role in acquired drug resistance, as increased autophagy has been observed in resistance to multiple anticancer agents. In this study, Dabrafenib was administered to melanoma cells with an RAF mutation, while Dacarbazine was given to cells with an Raf wild type. Both cell lines showed increased autophagy and FAO following treatment with the anticancer drugs. When FAO was blocked during drug treatment, melanoma cells became more susceptible to cell death. In xenograft models, B16F10 melanoma (Raf wild type) demonstrated regrowth due to acquired resistance after two weeks of Dacarbazine treatment. Conversely, a combination of Dacarbazine and the FAO inhibitors KN510 and KN713 (a combination of KN510 and KN713:KN510713) caused near-complete remission without regrowth. A375 melanoma (BRAF^V600E) developed resistance after four weeks of Dabrafenib treatment, yet the combination of Dabrafenib and KN510713 resulted in near-complete remission with no signs of regrowth. Based on these findings, combining FAO inhibitors with first-line therapies may be a promising approach for managing melanoma, regardless of RAF mutation status. Full article

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant therapeutic challenge, particularly when multiple resistance mechanisms, such as metallo-β-lactamases (MBLs) and Klebsiella pneumoniae carbapenemase (KPC), coexist. Case description: We describe a case of a 51-year-old male with a post-sternotomy surgical site infection and concurrent bacteremia caused by a CRKP. Sternal swab and mediastinal liquid culture results highlighted CRKP harboring bla_NDM and bla_KPC genes, while the blood isolate showed bla_CTX and bla_KPC, indicating phenotypic resistance to ceftazidime-avibactam. All the strains exhibited phenotypic susceptibility to meropenem-vaborbactam (MEV), despite having a high minimum inhibitory concentration. Following clinical failure of MEV-based therapy, combination treatment with aztreonam (ATM) and imipenem/cilastatin/relebactam (IMI/REL), plus gentamicin, was initiated. Therapy was well tolerated and resulted in microbiological eradication and full clinical recovery. The patient completed 49 days of ATM and IMI/REL without relapse over a 3-month follow-up period. This is, to the best of our knowledge, the first reported case of IMI/REL being used in combination with ATM. Full article

Nocardia, a rare but life-threatening pathogen, can invade multiple tissues and organs, such as lungs, brain, skin and soft tissue. In this study, we determined whether nitric oxide (NO) contributes to the severity of experimental pulmonary nocardiosis. BALB/c mice with or without aminoguanidine (AG) treatment were infected with N. farcinica through intranasal or intraperitoneal routes. Over experimental period, weight and mortality were monitored, and lung tissues were collected for NO production, cytokines detection, histopathological analysis, and bacterial load assessment. Next, alveolar MH-S macrophages were treated with various inhibitors to explore the impacts of NO, MAPK, and NF-κB against N. farcinica infection. AG treatment improved weight loss, lowered pulmonary bacterial load, and attenuated inflammatory response in infected mice. Similar effects were observed in alveolar MH-S macrophages. And all AG-treated mice survived infection. Furthermore, we suggest that NO is induced by N. farcinica through MAPK JNK and NF-κB signaling. Our study demonstrates the causative role of inducible NO on the severity of N. farcinica infection. Full article