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Bio-refining lignocellulosic resource offers a renewable and sustainable approach for producing biofuels and biochemicals. However, the conversion efficiency of lignocellulosic resource is still challenging due to the intrinsic inefficiency in co-utilization of xylose and glucose. In this study, the industrial bacterium Bacillus licheniformis was engineered for biorefining lignocellulosic resource to produce acetoin. First, adaptive evolution was conducted to improve acetoin tolerance, leading to a 19.6 % increase in acetoin production. Then, ARTP mutagenesis and 60Co-γ irradiation was carried out to enhance the production of acetoin, obtaining 73.0 g/L acetoin from glucose. Further, xylose uptake and xylose utilization pathway were rewired to facilitate the co-utilization of xylose and glucose, enabling the production of 60.6 g/L acetoin from glucose and xylose mixtures. Finally, this efficient cell factory was utilized for acetoin production from lignocellulosic hydrolysates with the highest titer of 68.3 g/L in fed-batch fermentation. This strategy described here holds great applied potential in the biorefinery of lignocellulose for the efficient synthesis of high-value chemicals.
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Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
Subject(s)
Lipid Metabolism , Mice, Inbred C57BL , Proteomics , Spinal Cord Injuries , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Animals , Mice , Lipid Metabolism/physiology , Female , Lipidomics , Transcriptome , MultiomicsABSTRACT
OBJECTIVE: Human T-cell leukemia virus type 1-associated myelopathy (HAM) is a chronic, progressive, inflammatory disease with unclear pathogenesis and no effective treatments. We aimed to investigate a novel mechanistic theory and treat HAM patients with rituximab, which can deplete CD20+ B lymphocytes in circulation. METHODS: Single-cell RNA sequencing (scRNA-seq) data was analyzed to identify HTLV-1-associated B cells and their effect on T cells. An observational analysis of our HAM cohort was conducted to elucidate changes in the immunological microenvironment of these patients. Peripheral blood mononuclear cells (PBMC) from HAM patients were isolated to explore the efficacy of B cell depletion in vitro. To assess the effect of B-cell depletion on HAM patients, eligible participants in our cohort received rituximab therapy (NCT04004819). RESULTS: ScRNA-seq results suggest a significant effect of HTLV-1-associated B cells on T cells. Additionally, HTLV-1 was found to infect B cells and depletion of B cells inhibited the proliferation of T cells. Number of B cells in HAM patients had positive correlation with the proviral load and infected cell counts. Depletion of B cells led to a reduction in HTLV-1 proviral load in vitro. Furthermore, in clinical trial, 14 HAM patients were enrolled. Three patients (21.4%) who received rituximab failed to achieve remission, compared to 24 (85.7%) patients received any other therapy that failed to achieve remission. With a low level of circulating B cells, the proportion of Ki67-positive cells in CD4+ T cells fell. INTERPRETATION: This study provided evidence that depleting B-lymphocytes is an innovative strategy for treating patients with HAM and broadens the understanding of the role of B cells in infectious immunity.
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Background: Accurate evaluation of atopic dermatitis (AD) severity is crucial to determine and adjust treatment options. Previous studies have found the product of Investigator's Global Assessment (IGA) and affected body surface area (BSA) to be a simple tool, which requires further verification. Objective: To determine the validity of IGA*BSA in assessing the severity of AD across all age, sex, BMI and disease severity groups. Method: We performed a retrospective study of AD using data from a national cohort (China Type II Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project). Results: Overall, 3051 participants were included in the final analysis. IGA*BSA correlated better with objective measures than with subjective measures. IGA*BSA significantly correlated with Eczema Area and Severity Index (EASI) (r = 0.81), which was stronger than either IGA or BSA alone with EASI, regardless of age, sex, Body Mass Index (BMI), and disease severity groups. Besides, IGA*BSA mild, moderate, and severe groups were associated with significantly higher scores of other assessments and had moderate to fair concordance with other assessments severity strata. At follow-up, the concordance of improvement between IGA*BSA 50/75/90 and EASI 50/75/90 was observed (ĸ = 0.65, 0.62, 0.58, respectively). Conclusion: IGA*BSA appears to be a valid objective assessment of AD severity and improvement over time across all age, sex, BMI, and disease severity subgroups in the clinical practice.
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BACKGROUND: Paclitaxel (PTX) is a cornerstone chemotherapy for Breast Cancer (BC), yet its impact is limited by emerging resistance. Elemene Injection (EI) has shown potential in overcoming chemotherapy resistance. However, the efficacy by which EI restores PTX sensitivity in BC and the implicated molecular mechanism remain uncharted. METHODS: Network pharmacology and bioinformatic analysis were conducted to investigate the targets and mechanisms of EI in overcoming PTX resistance. A paclitaxel-resistant MCF-7 cell line (MCF-7PR) was established. The efficacy of EI and/or PTX in inhibiting cell viability was evaluated using sulforhodamine B assay, while cell proliferation was assessed using EdU staining. Furthermore, protein and gene expression analysis was performed through Western blotting and qPCR. RESULTS: The EI containing three active components exhibited a multifaceted impact by targeting an extensive repertoire of 122 potential molecular targets. By intersecting with 761 differentially expressed genes, we successfully identified 9 genes that displayed a direct association with resistance to PTX in BC, presenting promising potential as therapeutic targets for the EI to effectively counteract PTX resistance. Enrichment analysis indicated a significant correlation between these identified targets and critical biological processes, particularly DNA damage response and cell cycle regulation. This correlation was further substantiated through meticulous analysis of single-cell datasets. Molecular docking analysis revealed robust binding affinities between the active components of the EI and the identified molecular targets. Subsequently, in vitro experiments unequivocally demonstrated the dose- and time-dependent inhibitory effects of the EI on both PTX-resistant and sensitive BC cell lines, effectively mitigating the resistance phenotype associated with PTX administration. Furthermore, our findings have indicated EI to effectively suppress the protein expression levels of AR and RUNX1 in MCF-7 and MCF-7PR cells under PTX treatment, as well as downregulate the mRNA expression levels of stem-like properties' markers, KLF4 and OCT4, in these cell lines. CONCLUSION: Elemene Injection (EI) application has exhibited a significant capability to mitigate PTX resistance in BC, which has been achieved through targeted suppression of the AR/RUNX1 axis, revealing a key strategy to overcome chemotherapeutic resistance.
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Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC. Methods: The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways. Results: Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-ß signaling loop. Conclusions: The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-ß signaling pathway.
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Acute ischemic stroke (AIS) patients with active COVID-19 infection often have more severe symptoms and worse recovery. COVID-19 infection can cause gut microbiota dysbiosis, which is also a risk factor for poor outcomes in AIS patients. However, the association between gut microbiota and functional outcomes among AIS patients with COVID-19 infection has not been fully clarified yet. In this study, we performed 16S rRNA gene sequencing to characterize the gut microbial community among AIS patients with acute COVID-19 infection, AIS patients with post-acute COVID-19 infection, and AIS patients without COVID-19 infection. We found that AIS patients with acute COVID-19 experienced poorer recovery and significant gut dysbiosis, characterized by higher levels of Enterobacteriaceae and lower levels of Ruminococcaceae and Lachnospiraceae. Furthermore, a shorter time window (less than 28 days) between COVID-19 infection and stroke was identified as a risk factor for poor functional outcomes in AIS patients with COVID-19, and the enrichment of Enterobacteriaceae was indicated as a mediator in the relationship between infection time window and poor stroke outcomes. Our findings highlight the importance of early intervention after COVID-19 infection, especially by regulating the gut microbiota, which plays a role in the prognosis of AIS patients with COVID-19 infection.IMPORTANCEThe gut microbiota plays an important role in the association between respiratory system and cerebrovascular system through the gut-lung axis and gut-brain axis. However, the specific connection between gut bacteria and the functional outcomes of acute ischemic stroke (AIS) patients with COVID-19 is not fully understood yet. In our study, we observed a significant decrease in bacterial diversity and shifts in the abundance of key bacterial families in AIS patients with acute COVID-19 infection. Furthermore, we identified that the time window was a critical influence factor for stroke outcomes, and the enrichment of Enterobacteriaceae acted as a mediator in the relationship between the infection time window and poor stroke outcomes. Our research provides a new perspective on the complex interplay among AIS, COVID-19 infection, and gut microbiota dysbiosis. Moreover, recognizing Enterobacteriaceae as a potential mediator of poor stroke prognosis offers a novel avenue for future exploration and therapeutic interventions.
Subject(s)
COVID-19 , Dysbiosis , Gastrointestinal Microbiome , Ischemic Stroke , Humans , COVID-19/complications , COVID-19/microbiology , COVID-19/epidemiology , Gastrointestinal Microbiome/physiology , Male , Female , Ischemic Stroke/microbiology , Middle Aged , Aged , SARS-CoV-2 , RNA, Ribosomal, 16S/genetics , Risk FactorsABSTRACT
OBJECTIVE: To explore the alleviating effect of standardized three-step nursing on perioperative pressure injury in patients with spinal fractures accompanied by spinal cord injury. METHODS: A retrospective analysis was conducted on the clinical data of 153 patients who underwent surgical treatment for spinal fracture accompanied by spinal cord injury in our hospital from January 2021 to January 2024. All patients met the criteria for inclusion and exclusion. According to the nursing interventions received during the perioperative period, the patients were divided into a control group (n = 76) and an observation group (n = 77). The control group received routine nursing interventions during the perioperative period, while the observation group received standardized three-step nursing interventions. The occurrence, severity, area, and pain [Visual Analog Scale (VAS)], coagulation indicators [prothrombin time (PT), fibrinogen (FIB), D-dimer (D-D)], activities of daily living [Barthel Index], and quality of life [General Quality of Life Inventory (GQOLI-74)] were compared between the two groups. RESULTS: (1) Occurrence and severity of perioperative pressure injury: in the control group, 18 cases of pressure injury occurred, including 5 cases of stage I, 11 cases of stage II, and 2 cases of stage III; in the observation group, 7 cases of pressure injury occurred, including 4 cases of stage I and 3 cases of stage II. The occurrence rate and severity of pressure injury in the observation group were lower than those in the control group (p < 0.05). (2) Area of injury and pain: The area of injury on the day of surgery and 5 days after surgery in the observation group was lower than that in the control group (p < 0.05); the VAS score 5 days after surgery in the observation group was lower than that in the control group (p < 0.05). (3) Coagulation indicators: 5 days after surgery, the levels of D-D and FIB in the observation group were lower than those in the control group, while PT was higher than that in the control group (p < 0.05). (4) Activities of daily living and quality of life: 3 months after surgery, the Barthel score and GQOLI-74 score in the observation group were higher than those in the control group (p < 0.05). CONCLUSION: Standardized three-step nursing can significantly reduce the occurrence rate, severity, and area of perioperative pressure injury in patients with spinal fracture accompanied by spinal cord injury, alleviate patient pain, improve coagulation function, and enhance levels of activities of daily living and quality of life.
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Biochar is regarded as a promising lithium-ion batteries anode material, owing to its high cost-effectiveness. However, the poor specific capacity and cycling stability have limited its practical applications. A straightforward and cost-efficient solvothermal method is presented for synthesizing Mn3O4/biochar composites in this study. By adjusting solvothermal temperatures, Mn3O4 with different morphology is prepared and anchored on the biochar surface (MKAC-T) to improve the electrochemical performance. Due to the morphological effect of nanospherical Mn3O4 on the biochar surface, the MKAC-180 anode material demonstrates outstanding reversible capacity (992.5 mAh/g at 0.2 A/g), significant initial coulombic efficiency (61.1 %), stable cycling life (605.3 mAh/g at 1.0 A/g after 1000 cycles), and excellent rate performance (385.8 mAh/g at 1.6 A/g). Moreover, electro-kinetic analysis and ex-situ physicochemical characterizations are employed to illustrate the charge storage mechanisms of MKAC-180 anode. This study provides valuable insights into the "structure-activity relationship" between Mn3O4 microstructure and electrochemical performance for the Mn3O4/biochar composites, illuminating the industrial utilization of biomass carbon anode materials.
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Chickpea is a field crop that is playing an emerging role in the provision of healthy and sustainable plant-based value-added ingredients for the food and nutraceutical industries. This article reviews the characteristics of chickpea (composition, health properties, and techno-functionality) and chickpea grain that influence their use as whole foods or ingredients in formulated food. It covers the exploitation of traditional and emerging processes for the conversion of chickpea into value-added differentiated food ingredients. The influence of processing on the composition, health-promoting properties, and techno-functionality of chickpea is discussed. Opportunities to tailor chickpea ingredients to facilitate their incorporation in traditional food applications and in the expanding plant-based meat alternative and dairy alternative markets are highlighted. The review includes an assessment of the possible uses of by-products of chickpea processing. Recommendations are provided for future research to build a sustainable industry using chickpea as a value-added ingredient. © 2024 Society of Chemical Industry.
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Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.
Subject(s)
Epithelial Cells , Intestinal Mucosa , Macrophages , Selenium , Trichothecenes , Animals , Trichothecenes/toxicity , Mice , Macrophages/metabolism , Macrophages/drug effects , Selenium/pharmacology , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Epithelial Cells/pathology , Macrophage Activation/drug effects , Mice, Inbred C57BL , Signal Transduction/drug effects , Ferroptosis/drug effects , Male , Phosphatidylinositol 3-Kinases/metabolismABSTRACT
BACKGROUND AND AIM: Diabetes-associated cognitive impairment (DCI) is a prevalent complication of diabetes. However, there is a lack of viable strategies for preventing and treating DCI. This study aims to explore the efficacy of baicalin (Bai) in attenuating DCI and elucidating the underlying mechanisms. EXPERIMENTAL PROCEDURE: GK rats fed a high-fat and high-glucose diet were utilized to investigate the therapeutic potential of Bai. Cognitive function was assessed using the Morris water maze and novel object recognition tests. To gain insight into the molecular mechanisms underlying Bai's neuro-protective effects, co-cultured BV2/HT22 cells were established under high-glucose (HG) stimulation. The modes of action of Bai were subsequently confirmed in vivo using the DCI model in db/db mice. KEY RESULTS: Bai restored cognitive and spatial memory and attenuated neuron loss, along with reducing expressions of Aß and phosphorylated Tau protein in diabetic GK rats. At the cellular level, Bai exhibited potent antioxidant and anti-inflammatory effects against HG stimulation. These effects were associated with the upregulation of Nrf2 and supressed Keap1 levels. Consistent with these in vitro findings, similar mechanisms were observed in db/db mice. The significant neuroprotective effects of Bai were abolished when co-administered with ATRA, a Nrf2 blocker, in db/db mice, confirming that KEAP1-Nrf2 signaling pathway was responsible for the observed effect. CONCLUSIONS AND IMPLICATIONS: Bai demonstrates a great therapeutic potential for attenuating DCI. The antioxidant defense and anti-inflammatory actions of Bai were mediated through the KEAP1-Nrf2 axis. These findings advance our understanding of potential treatment approaches for DCI, a common complication associated with diabetes.
Subject(s)
Cognitive Dysfunction , Flavonoids , NF-E2-Related Factor 2 , Neuroprotective Agents , Signal Transduction , Up-Regulation , Animals , Male , Mice , Rats , Antioxidants/pharmacology , Cell Line , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Flavonoids/pharmacology , Flavonoids/therapeutic use , Kelch-Like ECH-Associated Protein 1/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , NF-E2-Related Factor 2/metabolism , Rats, Wistar , Signal Transduction/drug effects , Up-Regulation/drug effectsABSTRACT
The conventional von Neumann architecture has proven to be inadequate in keeping up with the rapid progress in artificial intelligence. Memristors have become the favored devices for simulating synaptic behavior and enabling neuromorphic computations to address challenges. An artificial synapse utilizing the perovskite structure PbHfO3 (PHO) has been created to tackle these concerns. By employing the sol-gel technique, a ferroelectric film composed of Au/PHO/FTO was created on FTO/glass for the purpose of this endeavor. The artificial synapse is composed of Au/PHO/FTO and exhibits learning and memory characteristics that are similar to those observed in biological neurons. The recognition accuracy for both MNIST and Fashion-MNIST data sets saw an increase, reaching 92.93% and 76.75%, respectively. This enhancement resulted from employing a convolutional neural network architecture and implementing an improved stochastic adaptive algorithm. The presented findings showcase a viable approach to achieve neuromorphic computation by employing artificial synapses fabricated with PHO.
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AIM: Hypothermia poses a threat to the health and lives of newborns. Therefore, it is essential to identify the factors that influence neonatal hypothermia and provide targeted intervention suggestions for clinical practice to reduce its occurrence. METHODS: We conducted a literature search to identify factors influencing neonatal hypothermia and performed a meta-analysis to determine the prevalence of neonatal hypothermia and its associated factors. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort and case-control studies, while the Agency for Healthcare Research and Quality (AHRQ) was used to evaluate the quality of cross-sectional studies. RESULTS: Eighteen studies involving 44 532 newborns from 13 countries were included. The incidence of neonatal hypothermia was 52.5% (95% CI: 0.37, 0.68). Factors such as no skin-to-skin contact, prematurity, low birth weight, delayed breastfeeding, asphyxiation and resuscitation after birth, low APGAR score, not wearing a cap, and caesarean section were found to affect neonatal hypothermia. CONCLUSION: Multiple factors influence neonatal hypothermia, and clinicians can utilise these factors to develop targeted intervention measures to prevent and reduce the incidence of neonatal hypothermia.
Subject(s)
Hypothermia , Humans , Infant, Newborn , Hypothermia/epidemiology , Hypothermia/etiology , Hypothermia/prevention & control , Incidence , Risk FactorsABSTRACT
The research found that after doping with rare earth elements, a large number of electrons and holes will be produced on the surface of AlN, which makes the material have the characteristics of spontaneous polarization. A new type of ferroelectric material has made a new breakthrough in the application of nitride-materials in the field of integrated devices. In this paper, the application prospects and development trends of ferroelectric material ScAlN in memristors are reviewed. Firstly, various fabrication processes and structures of the current ScAlN thin films are described in detail to explore the implementation of their applications in synaptic devices. Secondly, a series of electrical properties of ScAlN films, such as the current switching ratio and long-term cycle durability, were tested to explore whether their electrical properties could meet the basic needs of memristor device materials. Finally, a series of summaries on the current research studies of ScAlN thin films in the synaptic simulation are made, and the working state of ScAlN thin films as a synaptic device is observed. The results show that the ScAlN ferroelectric material has high residual polarization, no wake-up function, excellent stability and obvious STDP behavior, which indicates that the modified material has wide application prospects in the research and development of memristors.
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Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.
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SiCp/Al composites offer the advantages of lightweight construction, high strength, and corrosion resistance, rendering them extensively applicable across various domains such as aerospace and precision instrumentation. Nonetheless, the interfacial reaction between SiC and Al under high temperatures leads to degradation in material properties. In this study, the interface segregation energy and interface binding energy subsequent to the inclusion of alloying elements were computed through a first-principle methodology, serving as a dataset for machine learning. Feature descriptors for machine learning undergo refinement via feature engineering. Leveraging the theory of machine-learning-accelerated first-principle computation, six machine learning models-RBF, SVM, BPNN, ENS, ANN, and RF-were developed to train the dataset, with the ANN model selected based on R2 and MSE metrics. Through this model, the accelerated computation of interface segregation energy and interface binding energy was achieved for 89 elements. The results indicate that elements including B, Si, Fe, Co, Ni, Cu, Zn, Ga, and Ge exhibit dual functionality, inhibiting interfacial reactions while bolstering interfacial binding. Furthermore, the atomic-scale mechanism elucidates the interfacial modulation of these elements. This investigation furnishes a theoretical framework for the compositional design of SiCp/Al composites.
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BACKGROUND: Incubation behaviour, an instinct for natural breeding in poultry, is strictly controlled by the central nervous system and multiple neuroendocrine hormones and neurotransmitters, and is closely associated with the cessation of egg laying. Therefore, it is essential for the commercial poultry industry to clarify the molecular regulation mechanism of incubation behaviour. Here, we used high-throughput sequencing technology to examine the pituitary transcriptome of Changshun green-shell laying hen, a local breed from Guizhou province, China, with strong broodiness, in two reproductive stages, including egg-laying phase (LP) and incubation phase (BP). We also analyze the differences in gene expression during the transition from egg-laying to incubation, and identify critical pathways and candidate genes involved in controlling the incubation behaviour in the pituitary. RESULTS: In this study, we demonstrated that a total of 2089 differently expressed genes (DEGs) were identified in the pituitary, including 842 up-regulated and 1247 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that steroid biosynthesis pathway and neuroactive ligand-receptor interaction were significantly enriched based on DEGs commonly identified in pituitary. Further analysis revealed that SRC, ITGB4, ITGB3, PIK3R3 and DRD2 may play crucial roles in the regulation of incubation behaviour. CONCLUSIONS: We identified 2089 DEGs and the key signaling pathways which may be closely correlated with incubation in Changshun green-shell laying hens, and clarified the molecular regulation mechanism of incubation behaviour. Our results indicate the complexity and variety of differences in reproductive behaviour of different chicken breeds.
Subject(s)
Chickens , Transcriptome , Animals , Female , Chickens/metabolism , Gene Expression Profiling , Pituitary Gland/metabolism , Hormones/metabolismABSTRACT
Protein function prediction is essential for disease treatment and drug development; yet, traditional biological experimental methods are less efficient in annotating protein function, and existing automated methods fail to fully leverage protein multisource data. Here, we present MSF-PFP, a computational framework that fuses multisource data features to predict protein function with high accuracy. Our framework designs specific models for feature extraction based on the characteristics of various data sources, including a global-local-individual strategy for local location features. MSF-PFP then integrates extracted features through a multisource feature fusion model, ultimately categorizing protein functions. Experimental results demonstrate that MSF-PFP outperforms eight state-of-the-art models, achieving FMax scores of 0.542, 0.675, and 0.624 for the biological process (BP), molecular function (MF), and cellular component (CC), respectively. The source code and data set for MSF-PFP are available at https://swanhub.co/TianGua/MSF-PFP, facilitating further exploration and validation of the proposed framework. This study highlights the potential of multisource data fusion in enhancing protein function prediction, contributing to improved disease therapy and medication discovery strategies.
Subject(s)
Proteins , SoftwareABSTRACT
Nanographene C222, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C222 difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C222 with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C222. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C222 to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C222 core, the resulting water-soluble C222 emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.