Browse Articles

Microbe-assisted fabrication of circularly polarized luminescent bacterial cellulosic hybrids

Unraveling the metabolic landscape of Exophiala spinifera strain FM: Model reconstruction, insights into biodesulfurization and beyond

Exophiala spinifera strain FM, a black yeast and melanized ascomycete, shows potential for oil biodesulfurization by utilizing dibenzothiophene (DBT) as its sole sulfur source. However, the specific pathway and enzymes involved in this process remain unclear due to limited genome sequencing and metabolic understanding of E. spinifera. In this study, we sequenced the complete genome of E. spinifera FM to construct the first genome-scale metabolic model (GSMM) for this organism. Through bioinformatics analysis, we identified genes potentially involved in DBT desulfurization and degradation pathways for hazardous pollutants. We focused on understanding the cost associated with metabolites in sulfur assimilation pathway to assess economic feasibility, optimize resource allocation, and guide metabolic engineering and process design. To overcome knowledge gaps, we developed a genome-scale model for E. spinifera, iEsp1694, enabling a comprehensive investigation into its metabolism. The model was rigorously validated against growth phenotypes and gene essentiality data. Through shadow price analysis, we identified costly metabolites such as 3’-phospho-5’-adenylyl sulfate, 5’-adenylyl sulfate, and choline sulfate when DBT was used as the sulfur source. iEsp1694 encompasses the degradation of aromatic compounds, which serves as a crucial first step in comprehending the pan metabolic capabilities of this strain.

RNAseq of peripheral blood mononucleated cells exposed to platelet-rich fibrin and enamel matrix derivatives

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data

Nitroxyl protects H9C2 cells from H/R-induced damage and inhibits autophagy via PI3K/Akt/mTOR pathway

Background Myocardial ischemia-reperfusion injury (MIRI) is an important complication in the treatment of heart failure, and its treatment has not made satisfactory progress. Nitroxyl (HNO) showed protective effects on the heart failure, however, the effect and underlying mechanism of HNO on MIRI remain largely unclear. Methods MIRI model in this study was established to induce H9C2 cell injury through hypoxia/reoxygenation (H/R) in vitro. The cell viability was assessed by cell counting kit-8 assay. The effect of HNO on the apoptosis was detected by flow cytometry. DCFH-DA fluorescent probe method was applied to detect the level of intracellular reactive oxygen species (ROS). The morphology of mitochondria and autophagosomes were observed by transmission electron microscopy. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were detected by western blot. Results The viability of H9C2 cells was significantly increased in the HNO group. HNO inhibited apoptosis and regulated expressions of key apoptotic protein, including Bax and Bcl-2. HNO reduced ROS levels and alleviated H/R-induced mitochondrial damage. HNO also inhibited autophagy and regulated expressions of key autophagy-related molecules, including LC3II, p62 and Beclin1. Further experiments demonstrated that the effects of HNO were mediated through upregulation of PI3K/Akt/mTOR pathway. Rapamycin reversed the inhibition of HNO on H/R-induced autophagy in H9C2 cells, which abrogated the protective effect of HNO. Conclusion This study provided the first evidence that HNO protected H/R-induced cardiomyocytes through inhibiting autophagy via the activation PI3K/Akt/mTOR pathway.

Dynamic simulation of breast behaviour during different activities based on finite element modelling of multiple components of breast

Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma

Abstract Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma. Integrative analysis shows that GTC-high tumors are enriched for lymphocytes and tumor associated macrophages (TAM) and express immune cell migration and activation programs. Specifically, GTCs constitute a distinct sub-cluster of the astrocyte-like tumor cell state that co-localizes with immune reactive TAMs. Neighboring GTCs and TAMs express receptor-ligand pairs characteristic of reactive astrogliosis and glial scarring, such as SPP1/CD44 and IL-1β/IL1R1. Collectively, we reveal that T cell confinement in IDHmt astrocytomas associates with GTC-TAM networks that mimic glial scarring mechanisms.

Comparative analysis of antibiotic resistance genes between fresh pig manure and composted pig manure in winter, China

Antibiotic resistance is a critical global public health issue. The gut microbiome acts as a reservoir for numerous antibiotic resistance genes (ARGs), which influence both existing and future microbial populations within a community or ecosystem. However, the differences in ARG expression between fresh and composted feces remain poorly understood. In this study, we collected eight samples from a farm in Kaifeng City, China, comprising both fresh and composted pig manure. Using a high-throughput quantitative PCR array, we analyzed differences in ARG expression between these two types of manure. Our findings revealed significant differences in ARG profiles, as demonstrated by principal coordinate analysis (PCoA). Further analysis identified 39 ARGs (log2FC > 1, p < 0.05) in composted pig manure, with 25 genes downregulated and 14 upregulated. Notably, tetB-01, blaOCH, and blaOXY were the most abundant in composted pig manure compared to fresh manure. Additionally, 16S rRNA species profiling revealed that the composting process significantly altered the microbial community structure, with an increased abundance of Firmicutes and a decreased abundance of Bacteroidetes in composted pig manure. In summary, composting substantially transforms both the microbial community structure and the ARG profile in pig manure, underscoring its potential role in modulating the dynamics of ARGs in agricultural environments.

A fair non-collateral consensus protocol based on Merkle tree for hierarchical IoT blockchain

Unlocking the potential of engineered immune cell therapy for solid tumors

Antibody response to Plasmodium vivax in the context of Epstein-Barr virus (EBV) co-infection: A 14-year follow-up study in the Amazon rainforest

Background To develop an effective vaccine against Plasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influence P. vivax antibody responses. Here, it was investigated whether EBV could impact the longevity of humoral immune response to P. vivax. Methodology/principal findings A 14-year follow-up study was carried out among long-term P. vivax-exposed Amazonian individuals (272, median age 35 years), and included 9 cross-sectional surveys at periods of high and low malaria transmission. The experimental approach focused on monitoring antibodies to the major blood-stage P. vivax vaccine candidate, the Duffy binding protein region II (DBPII-Sal1), including a novel engineered DBPII-based vaccine targeting conserved epitopes (DEKnull-2). In parallel, the status of EBV infection was determined over time by the detection of circulating EBV DNA (EBV-DNAemia) and EBV-specific antibodies to lytic (VCAp18) or latent (EBNA1) antigens. Regardless of the malaria transmission period, the results demonstrated that one or multiple episodes of EBV-DNAemia did not influence the longevity of DBPII immune responses to both strain-specific (Sal-1) or strain-transcending (DEKnull-2) antibodies. Also, the average time in which DBPII-responders lost their antibodies was unrelated to the EBV serostatus. Considering all malaria cases detected during the study, there was a predominance of P. vivax mono-infection (76%), with a positive correlation between malaria infection and EBV-DNAemia. Conclusions/significance In an immunocompetent P. vivax-exposed adult population neither sporadic episodes of EBV-DNAemia nor antibody responses to lytic/latent EBV antigens influence the longevity of both strain-specific and strain-transcending DBPII immune responses. Further studies should investigate the role of acute P. vivax infection in the activation of EBV replication cycle.

Salicylic acid confers cadmium tolerance in wheat by regulating photosynthesis, yield and ionic homeostasis

Efficient nonlinear function approximation in analog resistive crossbars for recurrent neural networks

A systematic review on the influence of coagulopathy and immune activation on New Onset Atrial Fibrillation in patients with sepsis

Introduction New Onset Atrial Fibrillation (NOAF) is the most common arrhythmia in intensive care. Complications of NOAF include thromboembolic events such as myocardial infarction and stroke, which contribute to a greater risk of mortality. Inflammatory and coagulation biomarkers in sepsis are thought to be associated with NOAF development. The aim of this systematic review and narrative synthesis is to identify inflammatory and coagulation biomarkers as predisposing risk factors for NOAF in sepsis. Methods Three databases (Medline, Cochrane Library, and Scopus) were searched using a predefined search strategy. Inclusion / exclusion criteria were applied, and quality assessments were performed using the Newcastle Ottawa Scale (NOS). Results We identified 1776 articles; and 12 articles were included in this review. 8 articles were retrospective observational studies and 4 were prospective observational studies. There was considerable heterogeneity between studies regarding outcomes, methodological design, quality, definitions and reported biomarkers of interest. There is evidence that C-reactive protein (CRP) is associated with NOAF, with hazard ratios 3.33 (3.32–3.35) p = 0.001 and odds ratios of 1.011 (1.008–1.014) p<0.001. International Normalised Ratio (INR) and fibrinogen may be associated with NOAF with odds ratios reported as 1.837 (1.270–2.656) p = 0.001 and 1.535(1.232–1.914) p<0.001 respectively. Conclusion Further research is required to confirm the association between inflammatory and coagulation biomarkers and the development of NOAF in sepsis. A broader evidence base will guide treatment strategies, improving the standard of care for patients who develop NOAF in sepsis. Furthermore, given the heterogeneity between studies consideration should be given to inclusion of immune biomarkers in future core outcome sets for trials investigating NOAF.

A deep learning analysis for dual healthcare system users and risk of opioid use disorder

Abstract The opioid crisis has disproportionately affected U.S. veterans, leading the Veterans Health Administration to implement opioid prescribing guidelines. Veterans who receive care from both VA and non-VA providers—known as dual-system users—have an increased risk of Opioid Use Disorder (OUD). The interaction between dual-system use and demographic and clinical factors, however, has not been previously explored. We conducted a retrospective study of 856,299 patient instances from the Washington DC and Baltimore VA Medical Centers (2012–2019), using a deep neural network (DNN) and explainable Artificial Intelligence to examine the impact of dual-system use on OUD and how demographic and clinical factors interact with it. Of the cohort, 146,688(17%) had OUD, determined through Natural Language Processing of clinical notes and ICD-9/10 diagnoses. The DNN model, with a 78% area under the curve, confirmed that dual-system use is a risk factor for OUD, along with prior opioid use or other substance use. Interestingly, a history of other drug use interacted negatively with dual-system use regarding OUD risk. In contrast, older age was associated with a lower risk of OUD but interacted positively with dual-system use. These findings suggest that within the dual-system users, patients with certain risk profiles warrant special attention.

A simple tool to evaluate the effectiveness of HIV care for settings with gaps in data availability (ESTIHIV)

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included. Of those, 93.8% were on ART (95% CI 93.3–94.2) and 76.7% were VS (95% CI 75.8–77.6). In 2022, we tested the tool in the RESPOND Cohort for all countries with more than 100 participants under follow-up in 2019. We included 26,426 HIV positive persons from clinics in 27 countries, 97.8% (95% CI 97.6-98.0) were on ART and 91.5% were VS (95% CI 91.2-91.8%). There was good agreement between the RESPOND country estimates of ART and VS and the estimations using a random sample calculated in ESTIHIV. With ESTIHIV, clinics can produce a reliable estimate in figures for reporting and for monitoring the effectiveness of care in their clinics.

The impact of teacher emotional support on learning engagement among college students mediated by academic self-efficacy and academic resilience

Abstract College students’ learning engagement not only significantly influences their academic performance but also plays a vital role in their future career development. Ensuring that students maintain high levels of engagement is essential for society’s goal of cultivating high-quality talent. Therefore, understanding the key factors that drive student engagement is critical for educators as they develop effective strategies to foster this engagement. This study aims to explore the mechanisms behind the relationship between teachers’ emotional support and college students’ learning engagement, with a focus on the mediating roles of academic self-efficacy and academic resilience. Accordingly, the following hypotheses are proposed: (1) Teacher emotional support positively predicts learning engagement; (2) Academic self-efficacy and academic resilience serve as mediators between teacher emotional support and learning engagement; (3) Academic self-efficacy and academic resilience function as sequential mediators in the relationship between teacher’ emotional support and learning engagement. This study utilized a random sampling method to survey 414 eligible college students from a university in western Shandong Province, China. Standardized scales were employed to measure teacher emotional support, learning engagement, academic self-efficacy, and academic resilience. For data analysis, Pearson correlation analysis was performed first, followed by the bias-corrected percentile Bootstrap method. (1) The study detected no significant systematic bias, and the correlations among teacher emotional support, learning engagement, academic self-efficacy, and academic resilience were all statistically significant. (2) Grounded in Self-Determination Theory, this study clarifies the relationship between teacher emotional support and learning engagement. The findings reveal that teacher emotional support positively predicts academic self-efficacy, academic resilience, and learning engagement. Similarly, both academic self-efficacy and academic resilience positively predict learning engagement, with academic self-efficacy also directly and positively predicting academic resilience. Notably, all proposed hypotheses were empirically supported. (3) The indirect effect through academic self-efficacy is 0.085, while the indirect effect through academic resilience is 0.121. Additionally, the combined indirect effect of both academic self-efficacy and academic resilience as sequential mediators is 0.059. (4) The cumulative total of all these indirect effects is 0.265. Based on Self-Determination Theory, we propose a sequential mediation model where teachers’ emotional support significantly and positively impacts students’ learning engagement, with academic self-efficacy and academic resilience acting as key mediators in this relationship. Additionally, teachers’ emotional support enhances students’ learning engagement by boosting their academic self-efficacy and reinforcing their academic resilience. These findings offer strong theoretical support for educational practice.

Adaptive weighted progressive iterative approximation based on coordinate decomposition

During the iterative process of the progressive iterative approximation, it is necessary to calculate the difference between the current interpolation curve and the corresponding data points, known as the adjustment vector. To achieve more precise adjustments of control points, this paper decomposes the adjustment vector into its coordinate components and introduces a weight for each component. By dynamically adjusting these weights, we can accelerate the convergence of iterations and enhance approximation accuracy. During the iteration, the weight coefficients are flexibly adjusted based on the error of the current iteration step, demonstrating the flexibility and precision of the geometric iterative method in addressing geometric approximation problems. Numerical experiment results indicate that this vector decomposition technique is a critical mathematical operation for improving algorithm efficiency and precisely adjusting the shapes of curves or surfaces to approximate the data set.

Examining the Influence of Alexithymia, Gender, and Age on Drug Use among Iranian Students: the Mediating Role of Emotion Regulation Difficulties

Modified musculofascial lengthening technique for submuscular ulnar nerve transposition in cubital tunnel syndrome

Objective Cubital tunnel syndrome is a common peripheral neuropathy of the upper extremity. Anterior transposition of the ulnar nerve is an established surgical treatment option for this condition. This study aimed to introduce a novel musculofascial lengthening technique that uses only a portion of the flexor-pronator muscle mass for submuscular anterior transposition of the ulnar nerve and investigate its clinical outcomes. Methods We evaluated 28 patients (29 cases; 1 patient had bilateral involvement) diagnosed with cubital tunnel syndrome who were treated with surgical decompression and submuscular anterior transposition of the ulnar nerve using our novel technique. Mean follow-up was 19.1 months (range, 12–31). Patient-reported outcomes were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ), Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, and numeric rating scale (NRS) for pain. Objective outcomes including light touch perception, static two-point discrimination, and grip strength were also assessed. Modified Bishop score and postoperative complications were also evaluated. Results BCTQ symptom severity and functional status scores, DASH score, and NRS for pain score showed significant improvement after surgery. Light touch perception, static two-point discrimination, and grip strength also significantly improved after surgery. All patients showed excellent or good results according to the modified Bishop scoring system. No recurrence or complications occurred. Conclusion Our novel musculofascial lengthening technique that uses only a portion of the flexor-pronator muscle mass for submuscular anterior transposition of the ulnar nerve reliably achieves good results with minimal complications in patients with cubital tunnel syndrome.