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Abstract The air traffic information network is fundamental for ensuring the efficient and safe operation of flights. However, with the increasing demands of air traffic services, the rigidity of the traditional air traffic information network has become increasingly pronounced. Network function virtualization (NFV) technology presents an effective solution to address this issue. Within the NFV environment, the deployment of service function chains (SFC) forms the basis for achieving end-to-end air traffic services. This paper addresses the low delay and high security requirements inherent in air traffic services and proposes an efficient and secure SFC deployment for delay optimization (ESSFCD-DO) method. Primarily, the paper conducts a theoretical analysis of SFC deployment, and derives four key principles related to SFC delay, security, and resource cost. Subsequently, based on these principles, the ESSFCD-DO method is developed, which encompasses the virtual network function (VNF) aggregation algorithm for security and resources cost optimization (VNFAA-SRCO), the VNF deployment algorithm based on topology aware (VNFD-TA), and the algorithm for deploying virtual links based on k-shortest path. Experimental results demonstrate that, in comparison to other SFC deployment methods within this domain, ESSFCD-DO achieves significant optimizations in terms of end-to-end delay of SFC and long-term revenue-cost ratio, while ensuring security and service request acceptance rate.

Abstract Targeted immunotherapies make substantial strides in clinical cancer care due to their ability to counteract the tumor's capacity to suppress immune responses. Advances in biomimetic technology with minimally immunogenic and highly targeted, are addressing issues of targeted drug delivery and disrupting the tumor's immunosuppressive environment to trigger immune activation. Specifically, the use of dendritic cell (DC) membranes to coat nanoparticles ensures targeted delivery due to DC's unique ability to activate naive T cells, spotlighting their role in immunotherapy aimed at disrupting the tumor microenvironment. The potential of DC's biomimetic membrane to mediate immune activation and target tumors is gaining momentum, enhancing the effectiveness of cancer treatments in conjunction with other immune responses. This review delves into the methodologies behind crafting DC membranes and the fusion of dendritic and tumor cell membranes for encapsulating therapeutic nanoparticles. It explores their applications and recent advancements in combating cancer, offering an all-encompassing perspective on DC biomimetic nanosystems, immunotherapy driven by antigen presentation, and the collaborative efforts of drug delivery in chemotherapy and photodynamic therapies. Current evidence shows promise in augmenting combined therapeutic approaches for cancer treatment and holds translational potential for various cancer treatments in a clinical setting. Graphical Abstract

Abstract Background Platycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited. Results This study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum. Conclusions The present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages.

Abstract Background Recent studies have highlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture’s (EA) impact on liver morphology and function in T2DM rats, furnishing experimental substantiation for its potential to stall MAFLD progression in T2DM. Methods T2DM rats were induced by a high-fat diet and a single intraperitoneal injection of streptozotocin, and then randomly assigned to five groups: the T2DM group, the electroacupuncture group, the metformin group, combination group of electroacupuncture and metformin, combination group of electroacupuncture and Compound C. The control group received a standard diet alongside intraperitoneal citric acid - sodium citrate solution injections. After a 6-week intervention, the effects of each group on fasting blood glucose, lipids, liver function, morphology, lipid droplet infiltration, and fibrosis were evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, and immunofluorescence were employed to gauge the expression of key molecules in AMPK-associated glycolipid metabolism, insulin signaling, autophagy, and fibrosis pathways. Additionally, transmission electron microscopy facilitated the observation of liver autophagy, lipid droplets, and fibrosis. Results Our studies indicated that hyperglycemia, hyperlipidemia and IR promoted lipid accumulation, pathological and functional damage, and resulting in hepatic steatosis and fibrosis. Meanwhile, EA enhanced the activation of AMPK, which in turn improved glycolipid metabolism and autophagy through promoting the expression of PPARα/CPT1A and AMPK/mTOR pathway, inhibiting the expression of SREBP1c, PGC-1α/PCK2 and TGFβ1/Smad2/3 signaling pathway, ultimately exerting its effect on ameliorating hepatic steatosis and fibrosis in T2DM rats. The above effects of EA were consistent with metformin. The combination of EA and metformin had significant advantages in increasing hepatic AMPK expression, improving liver morphology, lipid droplet infiltration, fibrosis, and reducing serum ALT levels. In addition, the ameliorating effects of EA on the progression of MAFLD in T2DM rats were partly disrupted by Compound C, an inhibitor of AMPK. Conclusions EA upregulated hepatic AMPK expression, curtailing gluconeogenesis and lipogenesis while boosting fatty acid oxidation and autophagy levels. Consequently, it mitigated blood glucose, lipids, and insulin resistance in T2DM rats, thus impeding liver steatosis and fibrosis progression and retarding MAFLD advancement.

Abstract Omniphobic membranes, due to their exceptional properties, have drawn significant attention for overcoming the bottleneck in membrane distillation (MD) technology. This study demonstrates an innovative method for fabricating an omniphobic membrane that is simple and facile compared to other methods such as wet/dry etching and photolithography. The surface morphology of springtails was imitated using electrospraying technique to coat a polyvinylidene fluoride substrate with concave-shaped polystyrene beads that were successfully developed by controlling the electrical traction (voltage) and air resistance (humidity). Then, the lipid coating of springtail surfaces was mimicked by dip-coating the membrane in a low-toxicity short-chain perfluoropolyether lubricant. The concave structure’s tiny air pockets increased membrane hydrophobicity significantly, indicated by the fact that the first round of water bouncing took only 16.3 ms. Finally, in MD treatment of seawater containing 1.0 mM sodium dodecyl sulfate, the optimized omniphobic membrane maintained a stable 99.9% salt rejection rate.

Abstract Background Infantile Juvenile polyposis of infantile (JPI) is a rare and aggressive form of juvenile polyposis syndrome (JPS) typically diagnosed in the first year of life. It often carries a poor prognosis due to chronic gastrointestinal bleeding, protein-losing enteropathy, malnutrition and immune deficiency. Case presentation We report a case of a girl initially presented with pallor at 7 months of age, which progressed to gastrointestinal bleeding and protein-losing enteropathy. Endoscopic examination, which included both upper gastrointestinal endoscopy and enteroscopy, showed diffuse polyposis. Histopathology results indicated the presence of juvenile polyps with no dysplasia in all removed polyps. Genetic testing identified a 2.1 Mb deletion on chromosome 10q23.2q23.31 involving the phosphatase and tensin homolog (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A) genes. Treatment with sirolimus initiated at 10 months of age led to a reduction in the need for blood and albumin infusions, improved patient growth, and quality of life. While the frequency of endoscopic evaluations decreased with sirolimus, regular endoscopic polypectomy every 5 months remained necessary. However, discontinuation of sirolimus resulted in polyp recurrence after 2 months due to pneumonia. Conclusion This case highlights sirolimus treatment can alleviate many complications of JPI, it does not eliminate the need for aggressive polypectomy.

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract With the increasing urban environmental problems, spontaneous vegetation has been gradually emphasized for high ecological value, whose distribution has been reported as strongly influenced by fine-scale environmental factors. As one of the major zones for urban spontaneous vegetation distribution, urban riparian corridors are well suited for research on the response of spontaneous plants to microhabitats. Taking the Wenyu River-North Canal in Beijing as the study site, we measured six microhabitat factors, including the level of maintenance and visitor activity, canopy density, litter thickness, and distance to water and road, to investigate their effects on spontaneous plant assemblages. The results showed that spontaneous plants respond significantly to fine-scale habitat variation, and were more responsive to human disturbance than other factors. Compared with diversity indicators, the functional trait compositions were more significantly correlated with microhabitat factors. Under lower maintenance of plants, the spontaneous communities had a higher invasion risk for plants. Thick litter can impede the occurrence of invasive species while favoring the growth of native ones. Our findings are important for furthering understanding of the spontaneous plant community establishment, and can serve as a good reference for the maintenance and management of spontaneous plants in urban riparian corridors.

Abstract Background Despite the use of targeted therapeutic approaches, T-cell acute lymphoblastic leukemia (T-ALL) is still associated with a high incidence of complications and a poor prognosis. Indisulam (also known as E7070), a newly identified molecular glue compound, has demonstrated increased therapeutic efficacy in several types of cancer through the rapid degradation of RBM39. This study aimed to evaluate the therapeutic potential of indisulam in T-ALL, elucidate its underlying mechanisms and explore the role of the RBM39 gene. Methods We verified the anticancer effects of indisulam in both in vivo and in vitro models. Additionally, the construction of RBM39-knockdown cell lines using shRNA confirmed that the malignant phenotype of T-ALL cells was dependent on RBM39. Through RNA sequencing, we identified indisulam-induced splicing anomalies, and proteomic analysis helped pinpoint protein changes caused by the drug. Comprehensive cross-analysis of these findings facilitated the identification of downstream effectors and subsequent validation of their functional roles. Results Indisulam has significant antineoplastic effects on T-ALL. It attenuates cell proliferation, promotes apoptosis and interferes with cell cycle progression in vitro while facilitating tumor remission in T-ALL in vivo models. This investigation provides evidence that the downregulation of RBM39 results in the restricted proliferation of T-ALL cells both in vitro and in vivo, suggesting that RBM39 is a potential target for T-ALL treatment. Indisulam’s efficacy is attributed to its ability to induce RBM39 degradation, causing widespread aberrant splicing and abnormal translation of the critical downstream effector protein, THOC1, ultimately leading to protein depletion. Moreover, the presence of DCAF15 is regarded as critical for the effectiveness of indisulam, and its absence negates the ability of indisulam to induce the desired functional alterations. Conclusion Our study revealed that indisulam, which targets RBM39 to induce tumor cell apoptosis, is an effective drug for treating T-ALL. Targeting RBM39 through indisulam leads to mis-splicing of pre-mRNAs, resulting in the loss of key effectors such as THOC1.

Abstract Tin dioxide is regarded as an alternative anode material rather than graphite due to its high theoretical specific capacity. Modification with carbon is a typical strategy to mitigate the volume expansion effect of SnO2 during the charge process. Strengthening the interface bonding is crucial for improving the electrochemical performance of SnO2/C composites. Here, SnO2-embedded reduced graphene oxide (rGO) composite with a low graphene content of approximately 5 wt.% was in situ synthesized via a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. The structural integrity of the SnO2/rGO composite is significantly improved by optimizing the Sn–O–C electronic structure with CTAB, resulting a reversible capacity of 598 mAh g−1 after 200 cycles at a current density of 1 A g−1. CTAB-assisted synthesis enhances the rate performance and cyclic stability of tin dioxide/graphene composites, and boosts their application as the anode materials for the next-generation lithium-ion batteries.

The surgical navigation system enhances surgical safety and accuracy by providing precise guidance. However, traditional pose estimation algorithms lack real-time performance and accuracy. To address this issue, a multi-average Long Short Term Memory (LSTM) prediction network is designed to maintain sensitivity in estimating the position of surgical instruments and track their random motion trends. Additionally, the spatial coordinates of positioning markers are applied back to the imaging plane, reducing the recognition range and improving algorithm running speed. Experimental results show that the average time of estimation is less than 1ms while ensuring the prediction effect.

Introduction: High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived ceramide-1-phosphate (C1P) has been demonstrated to offer protection against various pulmonary diseases, its effects on HAPE remain unclear. Objectives: Our study aimed to investigate the potential role of CERK-derived C1P in the development of HAPE and to reveal the molecular mechanisms underlying its protective effects. We hypothesized that CERK-derived C1P could protect against HAPE by stabilizing circadian rhythms and maintaining mitochondrial dynamics. Methods: To test our hypothesis, we used CERK-knockout mice and established HAPE mouse models using a FLYDWC50-1C hypobaric hypoxic cabin. We utilized a range of methods, including lipidomics, transcriptomics, immunofluorescence, Western blotting, and transmission electron microscopy, to identify the mechanisms of regulation. Results: Our findings demonstrated that CERK-derived C1P played a protective role against HAPE. Inhibition of CERK exacerbated HAPE induced by the hypobaric hypoxic environment. Specifically, we identified a novel mechanism in which CERK inhibition induced aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, inducing the circadian rhythm and triggering mitochondrial damage by controlling the expression of proteins required for mitochondrial fission and fusion. The decreased ARNTL caused by CERK inhibition impaired mitochondrial dynamics, induced oxidative stress damage, and resulted in defects in mitophagy, particularly under hypoxia. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, neutralized oxidative stress induced by CERK inhibition, and ultimately relieved HAPE. Conclusions: This study provides evidence for the protective effect of C1P against HAPE, specifically, through stabilizing circadian rhythms and maintaining mitochondrial dynamics. Exogenous C1P therapy may be a promising strategy for treating HAPE. Our findings also highlight the importance of the circadian rhythm and mitochondrial dynamics in the pathogenesis of HAPE, suggesting that targeting these pathways may be a potential therapeutic approach for this condition.

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.

Objective: Our objective was to explore the patterns of resting-state network (RSN) connectivity alterations and investigate how the influences of individual-level network connections on cognition varied across clinical stages without assuming a constant relationship. Methods: 108 PD patients with continuum of cognitive decline (PD-NC = 46, PD-MCI = 43, PDD = 19) and 34 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological tests. Independent component analysis (ICA) and graph theory analyses (GTA) were employed to explore RSN connection changes. Additionally, stage-dependent differential impact of network communication on cognitive performance were examined using sparse varying coefficient modeling. Results: Compared to HCs, the dorsal attention network (DAN) and dorsal sensorimotor network (dSMN) were central networks with decreased connections in PD-NC and PD-MCI stage, while the lateral visual network (LVN) emerged as a central network in patients with dementia. Additionally, connectivity of the cerebellum network (CBN) increased in the PD-NC and PD-MCI stages. GTA demonstrated decreased nodal metrics for DAN and dSMN, coupled with an increase for CBN. Moreover, the degree centrality (DC) values of DAN and dSMN exhibited a stage-dependent differential impact on cognitive performance across the continuum of cognitive decline. Conclusion: Our findings suggest that across the progression of cognitive impairment, the LVN gradually transitions into a core node with reduced connectivity, while the enhancement of connections in CBN diminishes. Furthermore, the non-linear relationship between the DC values of RSNs and cognitive decline indicates the potential for tailored interventions targeting specific stages.

Abstract Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5′ UTR, were specifically recognized by the m6A “reader” protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

Abstract Stag beetles (Coleoptera: Lucanidae) represent a significant saproxylic assemblage in forest ecosystems and are noted for their enlarged mandibles and male polymorphism. Despite their relevance as ideal models for the study of exaggerated mandibles that aid in attracting mates, the regulatory mechanisms associated with these traits remain understudied, and restricted by the lack of high-quality reference genomes for stag beetles. To address this limitation, we successfully assembled the first chromosome-level genome of a representative species Dorcus hopei. The genome was 496.58 Mb in length, with a scaffold N50 size of 54.61 Mb, BUSCO values of 99.8%, and 96.8% of scaffolds anchored to nine pairs of chromosomes. We identified 285.27 Mb (57.45%) of repeat sequences and annotated 11,231 protein-coding genes. This genome will be a valuable resource for further understanding the evolution and ecology of stag beetles, and provides a basis for studying the mechanisms of exaggerated mandibles through comparative analysis.

Objective: Freezing of gait (FOG), a specific survival-threatening gait impairment, needs to be urgently explored in patients with multiple system atrophy (MSA), which is characterized by rapid progression and death within 10 years of symptom onset. The objective of this study was to explore the topological organisation of both low- and high-order functional networks in patients with MAS and FOG. Method: Low-order functional connectivity (LOFC) and high-order functional connectivity FC (HOFC) networks were calculated and further analysed using the graph theory approach in 24 patients with MSA without FOG, 20 patients with FOG, and 25 healthy controls. The relationship between brain activity and the severity of freezing symptoms was investigated in patients with FOG. Results: Regarding global topological properties, patients with FOG exhibited alterations in the whole-brain network, dorsal attention network (DAN), frontoparietal network (FPN), and default network (DMN), compared with patients without FOG. At the node level, patients with FOG showed decreased nodal centralities in sensorimotor network (SMN), DAN, ventral attention network (VAN), FPN, limbic regions, hippocampal network and basal ganglia network (BG), and increased nodal centralities in the FPN, DMN, visual network (VIN) and, cerebellar network. The nodal centralities of the right inferior frontal sulcus, left lateral amygdala and left nucleus accumbens (NAC) were negatively correlated with the FOG severity. Conclusion: This study identified a disrupted topology of functional interactions at both low and high levels with extensive alterations in topological properties in MSA patients with FOG, especially those associated with damage to the FPN. These findings offer new insights into the dysfunctional mechanisms of complex networks and suggest potential neuroimaging biomarkers for FOG in patients with MSA.

Employing electric double-layer (EDL) capacitors to harvest low-grade heat (LGH) is a novel technique in the high-efficiency energy absorption field. This work reports the fabrication of a vertical thermoelectric cell, based on a nanoporous graphene electrode immersed in low-concentration saline solution, for use as thermo-charging supercapacitors to convert LGH to electricity via thermally induced voltage. Because of a large specific area and a large number of micropores of nanoporous graphene films, the effective thermoelectric coefficient of the thermoelectric cell containing 0.01 M KCl solution can reach as high as 4.73 mV/°C. However, many factors, such as electrode materials, electrolyte solutions, and energy conversion device components, determine the efficiency of a thermoelectric conversion device. In summary, the device has a lower internal resistance and higher output voltage when the concentration of KCl solution is 0.05 M, and demonstrates higher thermoelectric conversion efficiency. Moreover, improving the conductivity of the electrolyte solution without affecting the device output voltage is also a way to reduce the internal power consumption of the device. The specific power and thermoelectric conversion efficiency of the device are increased by several orders of magnitude when uniformly dispersed silver nanoparticles are added to the potassium chloride solution to enhance the conductivity of the solution. The specific power underwent an increase from 0.50 mW g−1 to 42.37 mW g−1, and the thermoelectric conversion efficiency also increased from 0.0022% to 0.1358%.

Abstract Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Abstract Background Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. Results Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. Conclusions ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Abstract Background Physiological and pathological cardiomyocyte hypertrophy are important pathophysiological processes of adult congenital heart disease-associated ventricular hypertrophy. Glutamic oxaloacetic transaminase (GOT) is a vital marker of myocardial injury. This study aimed to investigate the changes in GOT levels during physiological and pathological cardiomyocyte hypertrophy in rats. Methods RNA-seq analysis and colorimetric methods were used to evaluate the changes in GOT mRNA and activity, respectively. GOT2 protein expression was detected by western blotting and immunofluorescence. Hematoxylin-eosin and wheat germ agglutinin methods were used to observe changes in rat cardiomyocyte morphology. Results In juvenile rat hearts, GOT mRNA expression and activity, and GOT2 protein level increased with age-related physiological cardiomyocyte hypertrophy; however, GOT2 protein level was reduced in hypoxia-induced pathological cardiomyocyte hypertrophy. Conclusions GOT2 may regulate physiological and pathological myocardial hypertrophy in rats. We speculated that the low GOT2 level contributed to the rapid occurrence of pathological cardiomyocyte hypertrophy, causing strong plasticity of right ventricular cardiomyocytes in the early postnatal period and heart failure in adulthood.

Abstract Objectives This study aims to investigate the potential of radiomics with multiple parameters from conventional T1 weighted imaging (T1WI) and susceptibility weighted imaging (SWI) in distinguishing between idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA). Methods A total of 201 participants, including 57 patients with PD, 74 with MSA, and 70 healthy control (HCs) individuals, underwent T1WI and SWI scans. From the 12 subcortical nuclei (e.g. red nucleus, substantia nigra, subthalamic nucleus, putamen, globus pallidus, and caudate nucleus), 2640 radiomic features were extracted from both T1WI and SWI scans. Three classification models - logistic regression (LR), support vector machine (SVM), and light gradient boosting machine (LGBM) - were used to distinguish between MSA and PD, as well as among MSA, PD, and HC. These classifications were based on features extracted from T1WI, SWI, and a combination of T1WI and SWI. Five-fold cross-validation was used to evaluate the performance of the models with metrics such as sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC). During each fold, the ANOVA and least absolute shrinkage and selection operator (LASSO) methods were used to identify the most relevant subset of features for the model training process. Results The LGBM model trained by the features combination of T1WI and SWI exhibited the most outstanding differential performance in both the three-class classification task of MSA vs. PD vs. HC and the binary classification task of MSA vs. PD, with an accuracy of 0.814 and 0.854, and an AUC of 0.904 and 0.881, respectively. The texture-based differences (GLCM) of the SN and the shape-based differences of the GP were highly effective in discriminating between the three classes and two classes, respectively. Conclusions Radiomic features combining T1WI and SWI can achieve a satisfactory differential diagnosis for PD, MSA, and HC groups, as well as for PD and MSA groups, thus providing a useful tool for clinical decision-making based on routine MRI sequences.

Abstract Background Rhodococci are studied for their bacterial ligninolytic capabilities and proclivity to accumulate lipids. Lignin utilization is a resource intensive process requiring a variety of redox active enzymes and cofactors for degradation as well as defense against the resulting toxic byproducts and oxidative conditions. Studying enzyme expression and regulation between carbon sources will help decode the metabolic rewiring that stymies lignin to lipid conversion in these bacteria. Herein, a redox proteomics approach was applied to investigate a fundamental driver of carbon catabolism and lipid anabolism: redox balance. Results A consortium of Rhodococcus strains was employed in this study given its higher capacity for lignin degradation compared to monocultures. This consortium was grown on glucose vs. lignin under nitrogen limitation to study the importance of redox balance as it relates to nutrient availability. A modified bottom–up proteomics workflow was harnessed to acquire a general relationship between protein abundance and protein redox states. Global proteomics results affirm differential expression of enzymes involved in sugar metabolism vs. those involved in lignin degradation and aromatics metabolism. As reported previously, several enzymes in the lipid biosynthetic pathways were downregulated, whereas many involved in β-oxidation were upregulated. Interestingly, proteins involved in oxidative stress response were also upregulated perhaps in response to lignin degradation and aromatics catabolism, which require oxygen and reactive oxygen species and generate toxic byproducts. Enzymes displaying little-to-no change in abundance but differences in redox state were observed in various pathways for carbon utilization (e.g., β‑ketoadipate pathway), lipid metabolism, as well as nitrogen metabolism (e.g., purine scavenging/synthesis), suggesting potential mechanisms of redox-dependent regulation of metabolism. Conclusions Efficient lipid production requires a steady carbon and energy flux while balancing fundamental requirements for enzyme production and cell maintenance. For lignin, we theorize that this balance is difficult to establish due to resource expenditure for enzyme production and stress response. This is supported by significant changes to protein abundances and protein cysteine oxidation in various metabolic pathways and redox processes.

Abstract Background Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. Results Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Conclusion Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.

Objective: Baicalin, which is a key bioactive constituent obtained from Scutellaria baicalensis, has been utilized in traditional Chinese medicine for many centuries. Although it has been reported that Baicalin (BA) can inhibit the replication of the Hepatitis B virus (HBV), the exact mechanism behind this process remains unclear. Interferon-stimulated genes (ISGs) are crucial in the process of antiviral defense. We aim to investigate whether BA can regulate the expression of ISGs, and thereby potentially modulate the replication of HBV. Methods: The study involved the use of CRISPR/Cas9 technology to perform knockout experiments on TRIM25 and IFIT3 genes. The expression of these genes was confirmed through techniques such as immunoblotting or Q-PCR. The levels of HBsAg and HBeAg were measured using ELISA, and the expression of interferon-stimulated genes was detected using a luciferase assay. Results: It is interesting to note that several ISGs belonging to the TRIM family, including TRIM5, TRIM25, and TRIM14, were induced after BA treatment. On the other hand, members of the IFIT family were reduced by BA stimulation. Additionally, BA-mediated HBV inhibition was found to be significantly restored in HepG2 cells where TRIM25 was knocked out. Additional research into the mechanism of action of BA found that prolonged treatment with BA activated the JAK/STAT signaling pathway while simultaneously inhibiting the NF-kB pathway. Conclusion: The findings of our study indicate that TRIM25 has a significant impact on the regulation of HBV replication following BA treatment, providing additional insight into the mechanisms by which BA exerts its antiviral effects.

Abstract Natural language processing (NLP) based on deep learning provides a positive performance for generative dialogue system, and the transformer model is a new boost in NLP after the advent of word vectors. In this paper, a Chinese generative dialogue system based on transformer is designed, which only uses a multi-layer transformer decoder to build the system and uses the design of an incomplete mask to realize one-way language generation. That is, questions can perceive context information in both directions, while reply sentences can only output one-way autoregressive. The above system improvements make the one-way generation of dialogue tasks more logical and reasonable, and the performance is better than the traditional dialogue system scheme. In consideration of the long-distance information weakness of absolute position coding, we put forward the improvement of relative position coding in theory, and verify it in subsequent experiments. In the transformer module, the calculation formula of self-attention is modified, and the relative position information is added to replace the absolute position coding of the position embedding layer. The performance of the modified model in BLEU, embedding average, grammatical and semantic coherence is ideal, to enhance long-distance attention.

Objective Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR-106b-5p is an autophagy- and apoptosis-related microribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI. Methods The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction. In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in vivo, SCI rats were treated with EA for 7 days at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively. Results The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p. Conclusion EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.

Simple and scalable production of micro-supercapacitors (MSCs) is crucial to address the energy requirements of miniature electronics. Although significant advancements have been achieved in fabricating MSCs through solution-based printing techniques, the realization of high-performance MSCs remains a challenge. In this paper, graphene-based MSCs with a high power density were prepared through screen printing of aqueous conductive inks with appropriate rheological properties. High electrical conductivity (2.04 × 104 S∙m−1) and low equivalent series resistance (46.7 Ω) benefiting from the dense conductive network consisting of the mesoporous structure formed by graphene with carbon black dispersed as linkers, as well as the narrow finger width and interspace (200 µm) originating from the excellent printability, prompted the fully printed MSCs to deliver high capacitance (9.15 mF∙cm−2), energy density (1.30 µWh∙cm−2) and ultrahigh power density (89.9 mW∙cm−2). Notably, the resulting MSCs can effectively operate at scan rates up to 200 V∙s−1, which surpasses conventional supercapacitors by two orders of magnitude. In addition, the MSCs demonstrate excellent cycling stability (91.6% capacity retention and ~100% Coulombic efficiency after 10,000 cycles) and extraordinary mechanical properties (92.2% capacity retention after 5000 bending cycles), indicating their broad application prospects in flexible wearable/portable electronic systems.

The presence of gas in transmission fluid can disrupt the flow continuity, induce cavitation, and affect the transmission characteristics of the system. In this work, a gas void fraction model of gas–liquid two-phase flow in a transmission tube is established by taking ISO 4113 test oil, air, and vapor to accurately predict the occurrence, development, and end process of the cavitation zone as well as the transient change in gas void fraction. This model is based on the conservative homogeneous flow model, considering the temperature change caused by transmission fluid compression, and cavitation effects including air cavitation, vapor cavitation, and pseudo-cavitation. In this model, the pressure term is connected by the state equation of the gas–liquid mixture and can be applied to the closed hydrodynamic equations. The results show that in the pseudo-cavitation zone, the air void fraction decreases rapidly with pressure increasing, while in the transition zone from pseudo-cavitation to air cavitation, the air void fraction grows extremely faster and then increases slowly with decreasing pressure. However, in the vapor cavitation zone, the vapor void fraction rises slowly, grows rapidly, and then decreases, which is consistent with the explanation that rarefaction waves induce cavitation and compression waves reduce cavitation.

Abstract Background The differences in fat deposition sites exhibit varying degrees of systemic inflammatory responses and organ damage, especially in obese individuals with excessive visceral fat. Visceral fat, which is closely related to an increase in mortality rates related to heart and liver diseases. However, few studies have analysed the differences in heart and liver indicators and their correlation among groups based on the abdominal visceral fat area (AVFA). Objective Clarifying the differences in and correlations of heart and liver indicators among groups with different severities of AVFA by magnetic resonance imaging (MRI). Methods Sixty-nine subjects with obesity were enrolled. The study group consisted of forty-one individuals (AVFA ≥ 150 cm2), and the control group consisted of twenty-eight individuals (100 cm2 ≤ AVFA

Abstract One of the characteristics of leukemia is that it contains multiple rearrangements of signal transduction genes and overexpression of non-mutant genes, such as transcription factors. As an important regulator of hematopoietic stem cell development and erythropoiesis, LMO2 is considered an effective carcinogenic driver in T cell lines and a marker of poor prognosis in patients with AML with normal karyotype. LDB1 is a key factor in the transformation of thymocytes into T-ALL induced by LMO2, and enhances the stability of carcinogenic related proteins in leukemia. However, the function and mechanism of LMO2 and LDB1 in AML remains unclear. Herein, the LMO2 gene was knocked down to observe its effects on proliferation, survival, and colony formation of NB4, Kasumi-1 and K562 cell lines. Using mass spectrometry and IP experiments, our results showed the presence of LMO2/LDB1 protein complex in AML cell lines, which is consistent with previous studies. Furthermore, in vitro and in vivo experiments revealed that LDB1 is essential for the proliferation and survival of AML cell lines. Analysis of RNA-seq and ChIP-Seq results showed that LDB1 could regulate apoptosis-related genes, including LMO2. In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.

This study aims to investigate the effect of the ring plate on the mechanical performance of X-type tube-gusset joints. The failure modes, ultimate strengths, and failure mechanisms of X-joints with ring plates were investigated through experiments and finite element analyses. The results indicated that the ring plate and the chord within the effective range of the ring plate constituted the primary bearing structure of the X-joint. Increases in the ring plate thickness and width increased the ultimate strength of the X-joint. By considering the forces of the braces as a superposition of the bending moment and the force acting on the gusset of the X-joint, a simplified calculation method for the ultimate strength of X-joints was established. The derivation process was validated and refined through experiments and finite element analyses. Finally, a safe and reliable formula was derived for evaluating the ultimate strength of X-joints.

Background Skin flap transplantation is one of the effective methods to treat the diabetes-related foot ulceration, but the intrinsic damage to vessels in diabetes mellitus (DM) leads to the necrosis of skin flaps. Therefore, the discovery of a non-invasive and effective approach for promoting the survival of flaps is of the utmost importance. Electrical stimulation (ES) promotes angiogenesis and increases the proliferation, migration, and elongation of endothelial cells, thus being a potential effective method to improve flap survival. Objective The purpose of this study was to elucidate the mechanism used by ES to effectively restore the impaired function of endothelial cells caused by diabetes. Methods A total of 79 adult male Sprague-Dawley rats were used in this study. Gene and protein expression was assessed by PCR and western blotting, respectively. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the morphology and density of the microvessels in the flap. Results The optimal duration for preconditioning the flap with ES was 7 days. The flap survival area percentage and microvessels density in the DMES group were markedly increased compared to the DM group. VEGF, MMP2, and MMP9 protein expression was significantly upregulated. ROS intensity was significantly decreased and GSH concentration was increased. The expression of IL-1β, MCP‑1, cleaved caspase-3, and Bax were downregulated in the DMES group, while TGF-β expression was upregulated. Conclusions ES improves the angiogenesis in diabetic ischemic skin flaps by attenuating oxidative stress–mediated inflammation and apoptosis, eventually increasing their viability.

ABSTRACTIntroduction B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL.Methods In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines.Results MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition.Conclusion Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target.

Key points 1. SyMRI showed excellent performance in predicting disease progression in NPC. 2. T1_Kurtosis and ADC were independent predictors of progression-free survival. 3. T1_Kurtosis was lower in the non-disease progression group than the disease progression group. 4. Combination of SyMRI, DWI, and clinical factors could improve the predictive performance.

In recent years, the rapid development of exoplanet research has provided us with an opportunity to better understand planetary systems in the universe and to search for signs of life. In order to further investigate the prevalence of habitable exoplanets and to validate planetary formation theories, as well as to comprehend planetary evolution, we have utilized confirmed exoplanet data obtained from the NASA Exoplanet Archive database, including data released by telescopes such as Kepler and TESS. By analyzing these data, we have selected a sample of planets around F, G, K, and M-type stars within a radius range of 1 to 20 R⊕ and with orbital periods ranging from 0.4 days to 400 days. Using the IDEM method based on these data, we calculated the overall formation rate, which is estimated to be 2.02%. Then, we use these data to analyze the relationship among planet formation rates, stellar metallicity, and stellar gravitational acceleration (logg). We firstly find that the formation rate of giant planets is higher around metal-rich stellars, but it inhibits the formation of gas giants when logg > 4.5, yet the stellar metallicity seems to have no effect on the formation rate of smaller planets. Secondly, the host stellar gravitational acceleration affects the relationship between planet formation rate and orbital period. Thirdly, there is a robust power-law relationship between the orbital period of smaller planets and their formation rate. Finally, we find that, for a given orbital period, there is a positive correlation between the planet formation rate and the logg.

Wildfire causes environmental, economic, and human problems or losses. This study reviewed wildfires induced by lightning strikes. This review focuses on the investigations of lightning mechanisms in the laboratory. Also, the paper aims to discuss some of the modeling studies on lightning-induced wildfires at different geographical locations using satellite-recorded lightning data and different statistical analyses. This review established that irrespective of the different models used to predict lightning wildfires, there is still a lack of understanding of the lightning-strike ignition mechanism; few experiments have been modeled to establish the dynamics of lightning-strike ignition. Therefore, further research needs to be carried out in this area to understand lightning ignition. It was ascertained from the various statistical modeling that lightning-induced wildfires are exacerbated by the abundant availability of fuel with a lower moisture content and high lightning efficiency. Moreover, because of changes in the climate and weather conditions, i.e., harsh weather and climate conditions due to anthropogenic activities, lightning-induced ignition wildfires have increased over the years, and they are expected to increase in the future if the climate and weather conditions continue to aggravate. Although various modeling studies have identified that lightning-induced wildfires have increased recently, no preventive measures have been conclusively proposed to reduce lightning-caused wildfires. Hence, this aspect of research has to be given critical attention. This review presents information that gives a profound understanding of lightning-induced wildfires, especially factors that influence lightning wildfires, and the state-of-the-art research that has been completed to understand lightning-induced wildfires.

In recent years, with economic development, urbanization has been accelerating. In the past 100 years, the global average temperature has increased by 0.5°C, and according to the predictions of most global climate models, the temperature will continue to increase by 1.5°C to 3.0°C in the next 100 years. Under the influence of global warming, the urban heat island effect problem is becoming more and more serious, bringing much harm. Studying the thermal effect and its influencing factors is of great significance for sustainable urban development. In this study, the seasonal and interannual surface temperature changes of the study area are inverted based on the SW-TES algorithm, and the LST inversion of the algorithm is simply verified. At the same time, a cell dichotomous model was established to explore the influencing factors of the urban heat island effect and the influence of different land use types and normalized vegetation indices in the Hangzhou metropolitan area was analyzed. The results showed that the overall heating trend of the study area showed a heating trend, the expansion rate of regional construction land was relatively fast, and the scale of urban land was increasing. Based on the results of surface temperature changes of areas with different land types, we obtained the temperature trends of each land type [from 2005 to 2018] and found that there was a negative correlation between surface temperature and normalized vegetation index. This study provides a theoretical basis to evaluate the urban heat island effect and analyze factors that impact it and would promote sustainable urban development.

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

Abstract Background Magnetic resonance imaging (MRI) is commonly used for the diagnosis of nasopharyngeal carcinoma (NPC) and occipital clivus (OC) invasion, but a proportion of lesions may be missed using non-enhanced MRI. The purpose of this study is to investigate the diagnostic performance of synthetic magnetic resonance imaging (SyMRI) in differentiating NPC from nasopharyngeal hyperplasia (NPH), as well as evaluating OC invasion. Methods Fifty-nine patients with NPC and 48 volunteers who underwent SyMRI examination were prospectively enrolled. Eighteen first-order features were extracted from VOIs (primary tumours, benign mucosa, and OC). Statistical comparisons were conducted between groups using the independent-samples t-test and the Mann–Whitney U test to select significant parameters. Multiple diagnostic models were then constructed using multivariate logistic analysis. The diagnostic performance of the models was calculated by receiver operating characteristics (ROC) curve analysis and compared using the DeLong test. Bootstrap and 5-folds cross-validation were applied to avoid overfitting. Results The T1, T2 and PD map-derived models had excellent diagnostic performance in the discrimination between NPC and NPH in volunteers, with area under the curves (AUCs) of 0.975, 0.972 and 0.986, respectively. Besides, SyMRI models also showed excellent performance in distinguishing OC invasion from non-invasion (AUC: 0.913–0.997). Notably, the T1 map-derived model showed the highest diagnostic performance with an AUC, sensitivity, specificity, and accuracy of 0.997, 96.9%, 97.9% and 97.5%, respectively. By using 5-folds cross-validation, the bias-corrected AUCs were 0.965–0.984 in discriminating NPC from NPH and 0.889–0.975 in discriminating OC invasion from OC non-invasion. Conclusions SyMRI combined with first-order parameters showed excellent performance in differentiating NPC from NPH, as well as discriminating OC invasion from non-invasion.

Abstract Background Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease of nonspecific origin. This study used an RNA-Sequencing (RNA-Seq) approach to evaluate the transcriptomic landscape of a well-stratified treatment-naïve pediatric UC patient population by comparing them with healthy control children. The data were analyzed to evaluate the mechanisms driving UC-related intestinal inflammation and fibrosis. Methods Intestinal mucosal samples from five pediatric UC patients and five healthy controls were analyzed by RNA-Seq, and results were verified by qPCR. A CRISPR/Cas9 approach was used to knock out the expression of HLA-DRB5, and molecular biology techniques were used for additional mechanistic studies. Results In these analyses, 2290 genes were found to be differentially expressed between the UC and control samples, of which 1258 and 1032 were upregulated and downregulated, respectively. Gene Ontology analysis showed that these genes were enriched in extracellular matrix (ECM)-related processes and that 7 of 8 differentially expressed genes of interest (PIK3CD, IL1β, IL1α, TIMP1, MMP1, MMP12, COL6A3, and HLADRB5) were upregulated and involved in ECM-receptor interaction and inflammatory bowel disease-related pathways. Increased HLA-DRB5 expression driven by intestinal bacteria was found to promote IL-1α secretion, leading to intestinal inflammation and fibrosis, suggesting a possible target for the treatment of UC. Conclusion These data suggest that intestinal inflammation is present in pediatric UC patients for extended periods before the onset of symptoms, and intestinal fibrosis begins even during the early stages of UC. Intestinal bacteria were also found to trigger intestinal inflammation and fibrosis, with HLA-DRB5 playing a central role in this process.

Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients.

Abstract Early-stage fire-warning systems (EFWSs) have attracted significant attention owing to their superiority in detecting fire situations occurring in the pre-combustion process. Substantial progress on EFWSs has been achieved recently, and they have presented a considerable possibility for more evacuation time to control constant unintentional fire hazards in our daily life. This review mainly makes a comprehensive summary of the current EFWSs, including the working mechanisms and their performance. According to the different working mechanisms, fire alarms can be classified into graphene oxide-based fire alarms, semiconductor-based fire alarms, thermoelectric-based fire alarms, and fire alarms on other working mechanisms. Finally, the challenge and prospect for EFWSs are briefly provided by comparing the art of state of fire alarms. This work can propose a more comprehensive understanding of EFWSs and a guideline for the cutting-edge development direction of EFWSs for readers.

Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

Abstract The current understanding of lactate extends from its origins as a byproduct of glycolysis to its role in tumor metabolism, as identified by studies on the Warburg effect. The lactate shuttle hypothesis suggests that lactate plays an important role as a bridging signaling molecule that coordinates signaling among different cells, organs and tissues. Lactylation is a posttranslational modification initially reported by Professor Yingming Zhao’s research group in 2019. Subsequent studies confirmed that lactylation is a vital component of lactate function and is involved in tumor proliferation, neural excitation, inflammation and other biological processes. An indispensable substance for various physiological cellular functions, lactate plays a regulatory role in different aspects of energy metabolism and signal transduction. Therefore, a comprehensive review and summary of lactate is presented to clarify the role of lactate in disease and to provide a reference and direction for future research. This review offers a systematic overview of lactate homeostasis and its roles in physiological and pathological processes, as well as a comprehensive overview of the effects of lactylation in various diseases, particularly inflammation and cancer.

Given the energy crisis and severe environmental pollution, it is crucial to improve the energy utilization efficiency of integrated energy systems (IESs). Most existing studies on the optimal operation of IESs are based on the first law of thermodynamics without considering energy quality and direction attributes. The obtained strategies generally fail to accurately reflect the difference in energy quality. Based on the second law of thermodynamics, we first analyzed the energy quality coefficients of energy in different forms and expressed the exergy flow as the product of energy quality coefficients and energy flow. An exergy analysis model of the electric–gas–thermal integrated energy system was also established based on the energy network theory. Second, modeling and analyzing the dynamic characteristics of gas–thermal networks and the corresponding energy storage capacities were explored. Considering the dynamic characteristics of the gas–thermal pipeline network, the useful energy stored in the pipelines was analyzed based on the energy quality coefficients of natural gas and the thermal energy system, and the flexibility capacity of each subsystem was also analyzed in combination with the operation of units. A simulation analysis was then conducted on the electric–gas–thermal IES 39-20-6 system. The results demonstrated that from an energy perspective, the loss in the coupling equipment only accounts for 29.05% of the total energy losses, while from an exergy perspective, its proportion is as high as 46.47%. Besides, under the exergy analysis, when the dynamic characteristics of the gas–thermal pipeline network are taken into account, the wind curtailment rates of the system decrease from 11.22% to 8.27%.

High‐performance artificial muscle is always the pursuit of researchers for robotics. Herein, a bionic artificial muscle is reported called “ExoMuscle” mimicking the sarcomere in skeletal muscle with a bio‐inspired structure to contract “myofilaments” enabling the artificial muscle to mimic the architecture of muscle such as parallel, fusiform, convergent, and pennation and beyond the performance of skeletal muscle. The reported actuators excel in various aspects compared with skeletal muscle including actuation stress (0.41–0.9 MPa), strain (50%), optimal length, velocity‐independence output, power density (10.94 kW kg−1), and efficiency (69.11%). With its own adjustable pennation architecture, it achieves variable actuation stress up to 0.9 MPa meanwhile maintaining high efficiency. Furthermore, ExoMuscle highly conforms to the anatomical complexity of the human body to cooperate with skeletal muscles closely opening the door for bio‐robotics, especially wearable robots.

This paper explores the innovative concept of using wearable technologies as a medium for musical expression. Special emphasis is placed on a unique wearable device equipped with motion, touch, and acceleration sensors, which can be used as a wrist strap, hand strap, or surface drum pad. The aim is to create a new musical instrument that simplifies music learning and expression and makes them more intuitive. The wearable device contains 32 individual touch-sensitive pressure sensors, a nine-axis inertial-measurement-unit motion sensor, and various light-emitting diode and vibrational haptic-feedback components. The inclusion of tactile and intuitive features in the wearable device enhances the musical experience of users by enabling engaging interaction. Consequently, it is believed that this groundbreaking technology has significant potential to contribute to the field of music, providing musicians with a versatile and intuitive instrument that facilitates their creative expression.