Search

Abstract Terahertz frequency band (0.1 ~ 10 THz) can provide ultra-high transmitting rates for massive emerging applications. However, due to the radio frequency impairments and limited signal processing property of baseband devices, it is difficult for the current terahertz communication systems to be used in real applications. In this work, we report a 0.22 THz communication system, which can provide 84 Gbps air interface rate over 1.26 kilometers distance. Such a system is underpinned by three breakthroughs, namely, integrating the reported terahertz wireless communication system, redesigning the signal processing in baseband devices, and increasing the cut-off frequency and transmitting power of radio frequency component by parameter optimizing. Being applied to realize the real-time transmission of the uncompressed 8K ultra high-definition video in the 31st International University Sports Federation in Chengdu, China, this work is a leaping advancement to enable terahertz systems from experiment to promising applications.

Blood-brain barrier (BBB) damage is a major pathological change after intracerebral hemorrhage (ICH) and is both the cause and result of brain edema and the inflammatory response post-ICH. Cerebral immune cells (CICs), including microglia, pericytes, and astrocytes play a crucial role in the damage and protection of the BBB after ICH. Recent evidence suggests that peripheral immune cells (PICs) also play an important role in BBB damage and protection, brain edema, and neurological function impairment. Therefore, regulating interactions between glial cells and immune cells is expected to alleviate ICH-induced BBB damage. In this review, we first introduce the role of CICs, endothelial cells (ECs), oligodendrocytes (OLs), and PICs in BBB damage and protection after ICH, focusing on their polarization and inflammatory response. Next, we specifically discuss the crosstalk between CICs and PICs, such as the brain-spleen axis and brain-gut axis after ICH. Finally, we suggest that glial cells, PICs and, meningeal lymphatic system may be potential targets for alleviating BBB damage after ICH, and discuss some molecular targets and potential strategies for alleviating BBB damage after ICH by modulating CICs, ECs, and PICs.

Ecological changes have been observed to promote rates of lineage diversification, yet the precise roles of ecological factors, species evolution, and environmental variability in driving species diversity remain research hot spots. The association between ecological change and lineage diversification, particularly with regard to the size of the time scale, remains poorly understood. To explore whether ecological change facilitates species evolution, we focused on the unique family Paeoniaceae, which encompasses both herbaceous and woody taxa, to investigate the evolutionary rates. As a unique family characterized by a single genus of angiosperms and comprising various climatic types, the ecological niche changes of Paeoniaceae are closely associated with the evolution, making it an ideal model for conducting association analysis. In this study, we integrated the molecular fragments and ecological factors to explore the relationship between species evolution and niche changes in Paeoniaceae. The phylogenetic tree revealed that Paeoniaceae forms a sister relationship with Penthoraceae, Haloragidaceae, Iteaceae, Crassulaceae, and Saxifragaceae, constituting an independent clade based on the positive selection of molecular fragments including two protein-coding genes and eight non-coding regions. The divergence time was estimated to be between 102 and 116 Mya (Million years ago). The phylogenetic tree within Paeonia revealed a clear division into three groups: sections of Paeonia, Moutan, and Onaepia with high support values for each branch based on the ten positive selection of molecular fragments. The rapid rate of evolution observed in Paeonia, about 0-5 Mya. In addition, ecological niche modeling showed that the potential distributions for Paeonia expanded from middle Asia to eastern Asia, and from central North America to the Northern part of North America during the Last Glacial Maximum (LGM) to Mid Holocene (MID) period. This suggests that Paeonia continuously adapted to changing ecological environments over time. Compared to the rate of climatic niche divergence and lineage diversification, the ecological niche of Paeonia underwent significant changes during the period of 3-11 Mya, occurring 5 Mya earlier than the period of evolutionary rate change. These findings offer comprehensive insights into the relationship between niche change and the evolution of species, providing valuable perspectives for further ecological cultivation efforts.

Abstract Microbial processes are crucial in producing and oxidizing biological methane (CH4) in natural wetlands. Therefore, modeling methanogenesis and methanotrophy is advantageous for accurately projecting CH4 cycling. Utilizing the CLM‐Microbe model, which explicitly represents the growth and death of methanogens and methanotrophs, we demonstrate that genome‐enabled model parameterization improves model performance in four natural wetlands. Compared to the default model parameterization against CH4 flux, genomic‐enabled model parameterization added another contain on microbial biomass, notably enhancing the precision of simulated CH4 flux. Specifically, the coefficient of determination (R2) increased from 0.45 to 0.74 for Sanjiang Plain, from 0.78 to 0.89 for Changbai Mountain, and from 0.35 to 0.54 for Sallie's Fen, respectively. A drop in R2 was observed for the Dajiuhu nature wetland, primarily caused by scatter data points. Theil's coefficient (U) and model efficiency (ME) confirmed the model performance from default parameterization to genome‐enabled model parameterization. Compared with the model solely calibrated to surface CH4 flux, additional constraints of functional gene data led to better CH4 seasonality; meanwhile, genome‐enabled model parameterization established more robust associations between simulated CH4 production rates and environmental factors. Sensitivity analysis underscored the pivotal role of microbial physiology in governing CH4 flux. This genome‐enabled model parameterization offers a valuable promise to integrate fast‐cumulating genomic data with CH4 models to better understand microbial roles in CH4 in the era of climate change.

Abstract Thermal metamaterials are typically achieved by mixing different natural materials to realize effective thermal conductivities (ETCs) that conventional materials do not possess. However, the necessity for multifunctional design of metamaterials, encompassing both thermal and mechanical functionalities, is somewhat overlooked, resulting in the fixation of mechanical properties in thermal metamaterials designed within current research endeavors. Thus far, conventional methods have faced challenges in designing thermal metamaterials with configurable mechanical properties because of intricate inherent relationships among the structural configuration, thermal and mechanical properties in metamaterials. Here, a data‐driven approach is proposed to design a thermal metamaterial capable of seamlessly achieving thermal functionalities and harnessing the advantages of microstructural diversity to configure its mechanical properties. The designed metamaterial possesses thermal cloaking functionality while exhibiting exceptional mechanical properties, such as load‐bearing capacity, shearing strength, and tensile resistance, thereby affording mechanical protection for the thermal metadevice. The proposed approach can generate numerous distinct inverse design candidate topological functional cells (TFCs), designing thermal metamaterials with dramatic improvements in mechanical properties compared to traditional ones, which sets up a novel paradigm for discovering thermal metamaterials with extraordinary mechanical structures. Furthermore, this approach also paves the way for investigating thermal metamaterials with additional physical properties.

IntroductionMyocardial infarction (MI), a leading cause of heart failure, is characterized by the loss of cardiomyocytes, which severely limits the heart’s regenerative capacity. The Hippo pathway, which regulates cell proliferation and apoptosis, presents a therapeutic target for cardiac regeneration. This study explores the efficacy of Lats-IN-1, a LATS1/2 kinase inhibitor targeting the Hippo pathway, as a novel treatment for MI.MethodsUsing male C57BL/6 mice subjected to surgically induced MI, we administered Lats-IN-1 and evaluated the effects on cardiac function, infarct size, cardiomyocyte proliferation, and apoptosis through various assays and echocardiographic assessments.ResultsOur results demonstrate that Lats-IN-1 significantly improves cardiac function, as evidenced by enhanced ejection fraction and reduced ventricular dimensions. Additionally, Lats-IN-1 decreased infarct size and apoptosis rates while promoting cardiomyocyte proliferation. These findings suggest that Lats-IN-1 promotes cardiac repair and regeneration.DiscussionBy modulating the Hippo pathway and reducing apoptosis markers, Lats-IN-1 represents a promising therapeutic strategy for improving outcomes in heart diseases characterized by cardiomyocyte loss. This study highlights the critical role of the Hippo pathway in facilitating cardiac regeneration.

Summary: Pancreatic cancer (PC) is one of the most lethal malignancies and new therapeutic strategies are urgently needed. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) may be a potential option for cancer treatment, but its role in PC remains unknown. In this study, we first demonstrated through bioinformatics analysis that B3GNT5 was high expression in PC and predicted poor prognosis. We further constructed B3GNT5 overexpression or knockdown cell lines by employing lentivirus packaging techniques and confirmed that B3GNT5 could promote tumor cell viability and autonomous growth using cultured cells and vivo xenograft models. In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.

Abstract Background High-altitude pulmonary edema (HAPE) refers to the onset of breathlessness, cough, and fever at rest after arriving at high altitudes. It is a life-threatening illness caused by rapid ascent to high altitudes. Furosemide is controversial in HAPE treatment but is routinely used in China. Further research is needed to assess its efficacy and impact on HAPE management and prognosis. The aim of this study is to determine the effectiveness of furosemide for HAPE. Methods A retrospective was conducted to analysis of patients with HAPE admitted to the People’s Hospital of Shigatse City from January 2018 to September 2023. Patients were divided into furosemide group and non-furosemide group for further analysis. Clinical variables including demographic information, comorbidities, vital signs, inflammatory markers, biochemical analysis, CT severity score and prognostic indicators were collected. Results A total of 273 patients were enrolled, with 209 patients in the furosemide group and 64 patients in the non-furosemide group. The furosemide group showed a significantly decrease in CT severity scores compared to the non-furosemide group. Subgroup analysis showed that the longer the duration of furosemide use, the more pronounced the improvement in lung CT severity scores. But there were no significant differences in length of hospital stay and in-hospital mortality between the two groups. Conclusion Furosemide helps alleviate pulmonary edema in HAPE patients, but further research is needed to clarify its impact on prognosis.

Summary: Background: Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. Methods: Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3−/− mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. Findings: The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. Interpretation: Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. Funding: This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Abstract Nucleic acids are not only essential biomolecules that drive critical life processes such as growth, development, reproduction, inheritance, and mutation, but also serve as significant markers for disease diagnosis, pathogen identification, and cancer screening. Nevertheless, several challenges have hindered the widespread use of nucleic acids in biomedicine, such as susceptibility to degradation, limited cellular uptake efficiency, potential toxicity, and uncontrollable activity. Photo‐regulation offers an effective solution to address these challenges. It allows for the precise control of nucleic acid structure and function and enhances the stability and safety of their application in biomedicine. In this review, we systematically review the structural characteristics of the three primary photosensitive groups commonly used in the regulation of nucleic acid molecules (i.e., photocleavable molecules, photoisomerization molecules, and photo‐crosslinking molecules) under light irradiation. Subsequently, recent research advances in the development and application of photo‐modulation strategies based on these photosensitive molecules in antisense oligonucleotides, RNA interference, nucleic acid amplification, and CRISPR/Cas systems are outlined. Finally, we discuss the challenges faced in the widespread application of these photo‐regulatory strategies and outline potential future directions for their development.

BackgroundFangcang shelter hospitals are quarantine facilities offering primary medical treatment for mild and asymptomatic SARS-CoV-2 cases. Little is known about the age-specific prevalence of insomnia among patients in Fangcang shelter hospitals, particularly in older age groups.MethodsThis cross-sectional study was conducted in the three largest Fangcang shelter hospitals during the lockdown period, from March to May 2022, in Shanghai. The patients’ demographic and medical information was recorded. Insomnia was defined according to the prescriptions for zolpidem and estazolam. The overall and age-specific prevalence and the risk factors of insomnia were investigated through regression models.ResultsA total of 2,39,448 patients were included in this study (59.09% of the patients were male, the median age was 42, and 73.41% of the patients were asymptomatic), with the prevalence of insomnia being 3.1%. The prevalence of insomnia varied across different age groups (

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

Abstract Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)‐induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R‐induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation‐induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R‐induced ferroptosis. TPABTBP exhibits excellent LD‐specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super‐resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0–9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA‐approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Abstract In contrast to the wheel‐track trains, where the motor characteristics are considered a constant value, the motor characteristics of the medium‐speed maglev (MSM) trains are the dependent variable of the position. This article studies the integration of traction power control and train control for the MSM to minimize energy consumption. First, an innovative integrated energy‐efficient optimization model for MSM train control is constructed, considering the characteristics of the linear motors. Then, a multi‐level dynamic programming (DP) approach, which includes the train operation simulation with the linear motor, is developed to solve the optimization problem. Furthermore, a speed‐up strategy for the DP approach is proposed by a pre‐calculated target train speed band (TTSB). The results of numerical experiments show that the DP approach yields a more practical train speed profile. In contrast, the DP approach with the TTSB strategy can achieve a better trade‐off between solution accuracy and computational efficiency.

Frame-shear wall structures are widely used in high-rise buildings, and their thermal bridges account for a large portion of the entire exterior wall area. The purpose of this study was to investigate heat transfer of shear wall thermal bridge (SWTB) that influences the exterior wall of a building. A typical 3D COMSOL model of the SWTB junction was built, and indices were used to quantify its thermal characteristics of the SWTB junction. The results showed that the peak values and peak width of the heat flux at the interface of the exterior wall and thermal bridge increased with an increase in the thermal resistance of the SWTB. When the thermal resistance of the SWTB (Rtb) is greater than or equal to the thermal resistance of the exterior wall (Rw), the influencing area ${A_{inf}}$ no longer increases. In addition, the maximum error of replacing K2D with K1D discussed in this paper was 3.56%, which can be neglected in engineering applications in hot summer and cold winter climate zones. Finally, strategies to reduce the heat loss of the SWTB were proposed. The results of this study provide valuable data for engineers to evaluate the thermal characteristics of SWTB in building designs.

Earth Hour, a global mass effort coordinated to show concern for green urban construction and sustainable development, was first organized by the World Wildlife Fund in Australia in 2007 with a growing trend of participation worldwide. However, analysis of participation in Earth Hour based on a large population are sparse, with only a few studies reporting details in positive results without a clear pattern that explains the potential low participation. This study focuses on the non-participants and analyzed the reasons for low participation in Earth Hour using a questionnaire with 401 college students based on the socio-ecological model. Two aspects are explored: (1) social-demographic features; (2) psychosocial traits (environmental awareness, acceptance for law, social support from family and friends and knowledge about the event). Barriers toward participation are included as mediators to explain how these basic features change students’ decision on joining large-scale environmental campaign. A participation analysis method using binary logistic regression and one-way MANOVA is applied in data analysis. This study highlights that the irrelevance between students’ belief and practice on environmental protection should not be overlooked, and that college students are inclined to join in groups in relevant activities—conversely, herd effect could greatly reduce their willingness to participation. The findings of this study have wider implications for school educators, practitioners and organizations involved in pro-environmental career. This paper highlights that, from an international perspective, the essence of collective action with a similar nature to Earth Hour and contributes to a global dialogue on fostering sustainable behaviors.

Soil salinization poses a mounting global ecological and environmental threat. The identification of genes responsible for negative regulation of salt tolerance and their utilization in crop improvement through gene editing technologies emerges as a swift strategy for the effective utilization of saline-alkali lands. One efficient mechanism of plant salt tolerance is maintaining the proper intracellular K+/Na+ ratio. The Shaker K+ channels play a crucial role in potassium absorption, transport, and intracellular potassium homeostasis in plant cells. Here, the study presents the first genome-wide identification of Shaker K+ channels in Nicotiana tabacum L., along with a detailed bioinformatic analysis of the 20 identified members. Transcriptome analysis revealed a significant up-regulation of NtSKOR1B, an outwardly-rectifying member predominantly expressed in the root tissue of tobacco seedlings, in response to salt stress. This finding was then confirmed by GUS staining of ProNtSKOR1B::GUS transgenic lines and RT-qPCR analysis. Subsequently, NtSKOR1B knockout mutants (ntskor1) were then generated and subjected to salt conditions. It was found that ntskor1 mutants exhibit enhanced salt tolerance, characterized by increased biomass, higher K+ content and elevated K+/Na+ ratios in both leaf and root tissues, compared to wild-type plants. These results indicate that NtSKOR1B knockout inhibits K+ efflux in root and leaf tissues of tobacco seedlings under salt stress, thereby maintaining higher K+/Na+ ratios within the cells. Thus, our study identifies NtSKOR1B as a negative regulator of salt tolerance in tobacco seedlings.

ABSTRACTAntimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

The positive Arctic–methane (CH4) feedback forms when more CH4 is released from the Arctic tundra to warm the climate, further stimulating the Arctic to emit CH4. This study utilized the CLM-Microbe model to project CH4 emissions across five distinct Arctic tundra ecosystems on the Alaska North Slope, considering three Shared Socioeconomic Pathway (SSP) scenarios using climate data from three climate models from 2016 to 2100. Employing a hyper-resolution of 5 m × 5 m within 40,000 m2 domains accounted for the Arctic tundra’s high spatial heterogeneity; three sites were near Utqiaġvik (US-Beo, US-Bes, and US-Brw), with one each in Atqasuk (US-Atq) and Ivotuk (US-Ivo). Simulated CH4 emissions substantially increased by a factor of 5.3 to 7.5 under the SSP5–8.5 scenario compared to the SSP1–2.6 and SSP2–4.5 scenarios. The projected CH4 emissions exhibited a stronger response to rising temperature under the SSP5–8.5 scenario than under the SSP1–2.6 and SSP2–4.5 scenarios, primarily due to strong temperature dependence and the enhanced precipitation-induced expansion of anoxic conditions that promoted methanogenesis. The CH4 transport via ebullition and plant-mediated transport is projected to increase under all three SSP scenarios, and ebullition dominated CH4 transport by 2100 across five sites. Projected CH4 emissions varied in temperature sensitivity, with a Q10 range of 2.7 to 60.9 under SSP1–2.6, 3.8 to 17.6 under SSP2–4.5, and 5.7 to 17.2 under SSP5–8.5. Compared with the other three sites, US-Atq and US-Ivo were estimated to have greater increases in CH4 emissions due to warmer temperatures and higher precipitation. The fact that warmer sites and warmer climate scenarios had higher CH4 emissions suggests an intensified positive Arctic–CH4 feedback in the 21st century. Microbial physiology and substrate availability dominated the enhanced CH4 production. The simulated intensified positive feedback underscores the urgent need for a more mechanistic understanding of CH4 dynamics and the development of strategies to mitigate CH4 across the Arctic.

Early STEM education is crucial for later learning. This novel study utilised fNIRS to examine how STEM teaching methods (i.e., traditional, storytelling, storyboarding) affect neural activity synchronisation between teachers and students. Our results showed that left and right inferior frontal gyrus (IFG) for storytelling teaching versus traditional teaching, superior temporal gyrus for storyboard teaching versus traditional teaching, and left angular gyrus for storyboard and storytelling teaching were significant different in brain synchronisation. In the storytelling teaching condition, left supramarginal gyrus brain synchrony was found to improve STEM learning outcomes. In the storyboard teaching condition, IFG brain synchrony correlated positively with STEM learning improvement. The findings confirmed that story-based teaching and storyboarding can improve STEM learning efficacy at the neural level and unscored the significant role of neural synchronization as a predictor of learning outcomes.

Abstract Background The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. Method In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. Results Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. Conclusion Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

Abstract As non-renewable cultural heritages, murals have important implications in historical customs, religions, and philosophy as well as their aesthetic values. Recently, many murals are threatened by natural factors and human activities. During the past decades, there are increasing interest in the investigation of murals. Here we review the current status of murals and provide an up-to-date summary of achievements related to murals. The murals that draw the most attention are distributed in Mexico, Ireland, China, and Spain. The aesthetics, history, cultural, educational, and economic values of murals are comprehensively analyzed. The main research technologies used to detect the chemical compositions and physical structures of murals are also summarized. The restoration of murals includes several procedures such as stabilization, repair, surface cleaning, and pigment reconversion. Emerging technologies such as computer science benefit the research and conservation of murals. We also propose that tourism management and climate change should be incorporated into the conservation of murals in the future.

Abstract Background TP53 mutations are frequent in non‐small cell lung cancer (NSCLC). Different categories of TP53 mutations may be associated with survival in advanced NSCLC, but their effect on prognosis is diverse. To date, a comprehensive comparison of the relationship between different classes of TP53 alterations and survival in advanced NSCLC has rarely been performed. Moreover, the prognostic significance of a novel approach called the evolutionary action of TP53 (EAp53) in advanced NSCLC is unclear. Methods A total of 210 patients with NSCLC harboring TP53 mutation data were enrolled. Genomic and clinical data for the Memorial Sloan Kettering Cancer Center (MSKCC) cohort with advanced NSCLC were obtained from cBioPortal. Relationship between clinical characteristics and TP53 mutations was performed by Fisher's exact test or χ2 test. Overall survival (OS) analysis was evaluated using Kaplan–Meier method and Cox proportional hazards regression model. Results TP53 mutations were identified in 51.4% of NSCLC patients and were mainly located in exons 5, 7, and 8. The distribution patterns of missense and truncating mutations of TP53 were remarkably different. Among patients with advanced NSCLC who never received immune checkpoint inhibitor treatments, EAp53 high‐risk mutations were significantly associated with poor OS in both our cohort and the MSKCC cohort. Moreover, marked differences were observed in the mutational landscape between patients with EAp53 high‐risk mutations (HR group) and other patients (OT group). The HR group displayed higher mutation frequencies in the RTK, cell cycle, and DNA damage repair (DDR) pathways than the OT group. In addition, the tumor mutation burden in the HR group was significantly higher than that in the OT group. Conclusions This study provided important insights into the molecular‐clinical profile of TP53‐mutated NSCLC patients. Moreover, the data revealed that EAp53 high‐risk mutations were an independent prognostic factor for worse OS in advanced NSCLC.

IntroductionAcute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis.Methods and designA total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality.Ethics and disseminationThis protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.

AbstractHigh-resolution remote sensing images provide complete and detailed ground scenes. However, these complex and diverse details make it difficult to interpret large area objects and their small area details at a single granularity. Therefore, the method proposed in this paper refers to the principles of visual working memory, visual attention and visual reasoning, independently analyse the ground objects of different granularities, and integrates the recognition results of the different granularity ground objects to form accurate classification results. This multi-granularity classification strategy suppresses noise interference, protects typical edges, and highlights clear details. Experimental results with dataset of real land use survey projects, including images of different time, multiple perspectives, and different altitudes, The results show that the idea of combining unsupervised edge detection with neural network classification can greatly enhance the generalization ability and edge cognitive ability, making the classification accuracy reach 80% on average, with an improvement of about 5%.

Abstract Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson’s chi-squared test and the Mann–Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4–7 days, 8–14 days and 15–28 days after SAP onset were defined as stages 1–4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan–Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1–4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2–4 after onset. The validity of the above data was confirmed by Kaplan–Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis.

Targeted and controlled nitric oxide (NO) release is critical due to an extremely short half life and low bioavailability for treating cardiovascular diseases. To address this challenge, various sustained‐release precursors and NO donors activated by light, enzyme, or pH are developed. However, their efficacy is limited by the deep location and rapid blood flow of the heart. Herein, a platelet membrane‐coated nanoparticle (B‐P@PLT) is designed with a polymeric core loaded with BNN6, an ultrasound‐responsive NO donor, for the targeted treatment of myocardial ischemia reperfusion injury (MIRI). B‐P@PLT can specifically target the ischemic myocardium and release NO during ultrasound (US) irradiation, thereby increasing the local concentration of NO. B‐P@PLT + US shows promising results in promoting angiogenesis, reducing reactive oxygen species production, protecting cardiomyocytes both in vitro and in vivo, and ultimately decreasing cardiac injury and improving heart function in MIRI mice. These findings demonstrate a simple and noninvasive strategy for targeted delivery and controlled release of NO, highlighting its potential therapeutic application in MIRI.

The bone tumour microenvironment plays an essential role in multiple myeloma (MM) development. Here, the authors show that bone collagen degradation provides glycine to support MM progression through glutathione and purine synthesis.

Background Elaeocarpaceae is a vital family in tropical and subtropical forests. Compared with the important position of Elaeocarpaceae species in forest ecosystem and the concern of medicinal value, the most research on Elaeocarpaceae are classification and taxonomy. Molecular systematics has corrected the morphological misjudgment, and it belongs to Oxalidales. Phylogenetic and divergence time estimates of Elaeocarpaceae is mostly constructed by using chloroplast gene fragments. At present, although there are reports on the chloroplast structure of Elaeocarpaceae, a comprehensive analysis of the chloroplast structure of Elaeocarpaceae is lacking. Methods To understand the variation in chloroplast sequence size and structure in Elaeocarpaceae, the chloroplast genomes of nine species were sequenced using the Illumina HiSeq 2500 platform and further assembled and annotated with Elaeocarpus japonicus and Sloanea sinensis (family Elaeocarpaceae) as references. A phylogenomic tree was constructed based on the complete chloroplast genomes of the 11 species representing five genera of Elaeocarpaceae. Chloroplast genome characteristics were examined by using Circoletto and IRscope software. Results The results revealed the following: (a) The 11 sequenced chloroplast genomes ranged in size from 157,546 to 159,400 bp. (b) The chloroplast genomes of Elaeocarpus, Sloanea, Crinodendron and Vallea lacked the rpl32 gene in the small single-copy (SSC) region. The large single-copy (LSC) region of the chloroplast genomes lacked the ndhK gene in Elaeocarpus, Vallea stipularis, and Aristotelia fruticosa. The LSC region of the chloroplast genomes lacked the infA gene in genus Elaeocarpus and Crinodendron patagua. (c) Through inverted repeat (IR) expansion and contraction analysis, a significant difference was found between the LSC/IRB and IRA/LSC boundaries among these species. Rps3 was detected in the neighboring regions of the LSC and IRb regions in Elaeocarpus. (d) Phylogenomic analysis revealed that the genus Elaeocarpus is closely related to Crinodendron patagua on an independent branch and Aristotelia fruticosa is closely related to Vallea stipularis, forming a clade with the genus Sloanea. Structural comparisons showed that Elaeocarpaceae diverged at 60 Mya, the genus Elaeocarpus diverged 53 Mya and that the genus Sloanea diverged 0.44 Mya. These results provide new insight into the evolution of the Elaeocarpaceae.

Sepsis-induced acute kidney injury (AKI) is one of the important causes of increased mortality in sepsis patients. Long non-coding RNA (lncRNA) is believed to play a vital function in the progression of AKI. However, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) has not been fully elucidated. NEAT1 was overexpressed and miR-22-3p was underexpressed in sepsis patients and lipopolysaccharide (LPS)-induced AKI cell models. Knockdown of NEAT1 could promote viability and suppress apoptosis and the inflammatory response in LPS-induced HK2 cells. MiR-22-3p could be sponged by NEAT1, and its inhibitor reversed the inhibition effect of NEAT1 silencing on LPS-induced HK2 cell injury. CXCL12 could be targeted by miR-22-3p, and its overexpression reversed the suppression effect of miR-22-3p on LPS-induced HK2 cell injury. Silenced NEAT1 could restrain the activity of the NF-B signaling pathway, and miR-22-3p inhibitor or CXCL12 overexpression could reverse this effect. In addition, NEAT1 knockdown alleviated the inflammation response of cecal ligation and puncture (CLP) mouse models. In summary, our data showed that NEAT1 promoted LPS-induced HK2 cell injury via regulating the miR-22-3p/CXCL12/NF-B signaling pathway, suggesting that NEAT1 knockdown might be a potential pathway for alleviating sepsis-induced AKI.

Automatic heavy-haul train (HHT) operation technology has recently received considerable attention in the field of rail transportation. In this paper, a discrete-time-based mathematical formulation is proposed to address the speed profile optimization problem in order to ensure the safe, efficient, and economical operation of heavy-haul trains (HHTs). Due to the presence of long and steep downgrades (LSDs) on some heavy-haul lines, the brake forces of the HHT are typically jointly determined by air braking and electric braking. The time characteristics of the air braking, such as the command delay and the change process caused by the air pressure, are taken into account, and then formulas are presented to calculate the air brake force. In addition, the influence of the neutral section on the control of the electric braking is considered via space-based constraints. The resulting problem is a nonlinear optimal control problem. To achieve linearization, auxiliary 0-1 binary variables and the big-M approach are introduced to transform the nonlinear constraints regarding slope, curve, neutral section, air brake force, and air-filled time into linear constraints. Moreover, piecewise affine (PWA) functions are used to approximate the basic resistance of the HHT. Finally, a mixed integer linear programming (MILP) model is developed, which can be solved by CPLEX. The experiments are carried out using data from a heavy-haul railway line in China, and the results show that the proposed approach is effective and flexible.

Wetlands account for up to 70% of the natural source of methane (CH4) in terrestrial ecosystems on a global scale. Soil microbes are the ultimate producers and biological consumers of CH4 in wetlands. Therefore, simulating microbial mechanisms of CH4 production and consumptionwould improve the predictability of CH4 flux in wetland ecosystems. In this study, we applied a microbial-explicit model, the CLM-Microbe, to simulate CH4 flux in three major natural wetlands in northeastern China. The CLM-Microbe model was able to capture the seasonal variation of gross primary productivity (GPP), dissolved organic carbon (DOC), and CH4 flux. The CLM-Microbe model explained more than 40% of the variation in GPP and CH4 flux across sites. Marsh wetlands had higher CH4 flux than mountain peatlands. Ebullition dominated the CH4 transport pathway in all three wetlands. The methanogenesis dominates while methanotroph makes a minor contribution to the CH4 flux, making all wetlands a CH4 source. Sensitivity analysis indicated that microbial growth and death rates are the key factors governing CH4 emission and vegetation physiological properties (flnr) and maintenance respiration predominate GPP variation. Explicitly simulating microbial processes allows genomic information to be incorporated, laying a foundation for better predicting CH4 dynamics under the changing environment.

ABSTRACT Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to our knowledge, the integration of these factors has not been investigated in insomnia. Here, we explored the correlations across gut microbiota, serum metabolism, and inflammatory factors in insomnia. Our results showed that the composition and structure of gut microbiota and metabolism in insomnia patients were different from healthy controls. Compared to healthy controls, the relative abundances of Lactobacillus, Streptococcus, and Lactobacillus crispatus were significantly increased in insomniacs. There were five metabolic pathways in insomniacs (glycerophospholipid metabolism; glutathione metabolism; nitrogen metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis) significantly different between the two groups. Moreover, we found that IL-1β levels were significantly higher in insomnia patients while TNF-α was significantly reduced. We further identified that the changes in the level of IL-1β and TNF-α were associated with some specific bacteria and metabolites, such as Prevotella amnii, Prevotella buccalis, Prevotella timonensis, and Prevotella colorans. Mediation analysis further determined that the immune factors and metabolites could mediate the relationship between gut microbes and insomnia. IMPORTANCE Our study indicated that systematic inflammation and metabolites might be a pathway linking the gut microbiome with insomnia. These findings provide new insights and a better understanding of gut microbiota's role in insomnia as well as potential novel microbiome-related etiologies for insomnia.

BackgroundSepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis.Methods and designHere, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events.ConclusionThe findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis.Clinical trial registration[http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

The Natural Forest Protection Project (NFPP) is an ecological restoration project aimed at safeguarding natural forests, and is one of China’s six main forestry initiatives. The upper reaches of the Yangtze River represent the main distribution area of natural forests in China, and are an important area for the implementation of the NFPP. A systematic assessment of forest ecosystem changes in the upper Yangtze River region before and after implementation of the NFPP is of great scientific significance for the improvement of the project implementation effect, regional ecological protection, and further protection and restoration of natural forest resources. This study uses the NFPP area in the Yangtze River’s upper reaches as the study area; the data are primarily derived from the 1998 and 2020 forest resources category II survey data, long-term monitoring data from forest ecological stations, and public social data published by authoritative Chinese organizations. Based on the above data, we used the full index system of forest ecosystem services, continuous observation, and inventory system with the distributed measurement method to analyze the dynamic changes in forest ecosystem services in the study area in terms of three aspects: physical quality, value quality, and dominant function. The results of the study show that: (1) over the studied time scale, compared to the 1998 baseline, the physical quantities (soil erosion control, water regulation, and PM10 retention) and value of each service function of the forest ecosystem in the upper reaches of the Yangtze River project area in 2020 showed a significant increasing trend; (2) at the spatial scale, changes in forest ecosystem service functions in the upper reaches of Yangtze River under the NFPP showed significant spatial heterogeneity from 1998 to 2020; (3) in 2020, the total value of forest ecosystem services in the study area was 3,261,161,000,000 yuan/a, of which the functional value of biodiversity conservation was 1,294,426,000,000 yuan/a and the functional value of water conservation was 841,069,000,000 yuan/a, indicating that the forest ecosystem of the study area plays an important role as a “green gene pool” and “green water reservoir”; (4) the forest ecosystem service functions of the NFPP in the upper reaches of Yangtze River are intricately tied to forest resource features such as forest area, forest volume, age-group structure of arbor forest, etc., which influence the physical quantity and value of each forest ecosystem service function to varying degrees. In addition to illustrating the amazing efficiency of the natural forest preservation initiative, this study provides a scientific foundation for future natural forest resource conservation and restoration. It can serve as a reference for the project’s subsequent development as well to provide scientific foundations and guidance for the development of the natural forest protection and restoration program and to promote the protection and restoration of more natural forest resources.

The seismic records in the Cambrian southwest depression of the Tarim Basin exhibit discrepancies when compared to the actual geological setting, which is caused by the presence of multiples. Despite the application of the Radon transform, multiple interferences persist beneath the Cambrian salt in the pre-stack data, with significant variations in energy and frequency across the horizontal direction. In addition, other multiple suppression methods are also difficult to handle this problem. To address this issue, we have developed an iterative virtual event internal multiple suppression method for post-stack data. This novel algorithm extends the traditional virtual event internal multiple suppression approach, eliminating the need for data regularization and avoiding the problem of the traditional virtual events method requiring sequential extraction of primaries from relevant layers, which greatly improves computational efficiency and simplifies the implementation steps of the traditional method. Numerical experiments demonstrate the efficacy of our method in suppressing internal multiples in both synthetic and field data while preserving primary signals. When applied to real seismic data profiles, the iterative method yields structural characteristics that align more closely with sedimentary laws and reduces disparities in energy and frequency of multiples along the horizontal axis. Consequently, our method provides a robust foundation for subsequent hydrocarbon source rock prediction.

Oligotrophic marine environments are ecological funnels in marine ecosystems and are essential for maintaining the health and balance of the entire marine ecosystem. Bacterial communities are one of the most important biological populations, which can survive in low-nutrient environments and perform a variety of important ecological functions, such as decomposing and absorbing organic waste in the ocean and converting nitrogen from the atmosphere into a usable nitrogen source, thus maintaining the health of marine ecosystems. The bacterioplankton community composition and potential function were analyzed using 16S rRNA gene amplicon sequencing in oligotrophic coral reef sea areas. The diversity of the bacterial community exhibited significant differences between the four studied regions. Proteobacteria (38.58–62.79%) were the most abundant in all sampling sites, followed by Cyanobacteria (15.41–37.28%), Bacteroidota (2.39–6.67%), and Actinobacteriota (0.45–1.83%). Although bacterioplankton communities presented no difference between surface and bottom water regarding community richness and α-diversity, the bacterial community composition presented significant differences between surface and bottom water regarding β-diversity. Alteromonadales, Rhodospirllales, and Chloroplast were identified as the significantly different communities between the surface and bottom (Q value < 0.01). Bacterial community distribution in different regions was mainly affected by pH, dissolved oxygen, and nutrients. Nitrite ammonification, chitinolysis, predatory or exoparasitic, chloroplasts, chemoheterotrophy, aerobic chemoheterotrophy, phototrophic, compound degradation (mostly nutrients and pollutants), nitrogen cycle, fermentation, and intracellular parasitism were the dominant functions in the four regions.

Abstract Background Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Bacteria within biofilms are 10- to 1000-fold more resistant to antibiotics, making it challenging but imperative to develop new therapeutics that can disperse biofilms and eradicate infection. Gram-negative bacteria produce outer membrane vesicles (OMV) that play critical roles in communication, genetic exchange, cargo delivery, and pathogenesis. We have previously shown that OMVs derived from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi. Results Here, we examine the antibiofilm activity of Burkholderia thailandensis OMVs against the oral biofilm-forming pathogen Streptococcus mutans. We demonstrate that OMV treatment reduces biofilm biomass, biofilm integrity, and bacterial cell viability. Both heat-labile and heat-stable components, including 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline and long-chain rhamnolipid, contribute to the antibiofilm activity of OMVs. When OMVs are co-administered with gentamicin, the efficacy of the antibiotic against S. mutans biofilms is enhanced. Conclusion These studies indicate that bacterial-derived OMVs are highly effective biological nanoparticles that can inhibit and potentially eradicate biofilms.

Abstract Background Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). Methods However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COAD patients with prognostic information. Results A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COAD patients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells. Conclusion These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients.

Spatial heterogeneity in methane (CH4) flux requires a reliable upscaling approach to reach accurate regional CH4 budgets in the Arctic tundra. In this study, we combined the CLM-Microbe model with three footprint algorithms to scale up CH4 flux from a plot level to eddy covariance (EC) tower domains (200 m × 200 m) in the Alaska North Slope, for three sites in Utqiaġvik (US-Beo, US-Bes, and US-Brw), one in Atqasuk (US-Atq) and one in Ivotuk (US-Ivo), for a period of 2013–2015. Three footprint algorithms were the homogenous footprint (HF) that assumes even contribution of all grid cells, the gradient footprint (GF) that assumes gradually declining contribution from center grid cells to edges, and the dynamic footprint (DF) that considers the impacts of wind and heterogeneity of land surface. Simulated annual CH4 flux was highly consistent with the EC measurements at US-Beo and US-Bes. In contrast, flux was overestimated at US-Brw, US-Atq, and US-Ivo due to the higher simulated CH4 flux in early growing seasons. The simulated monthly CH4 flux was consistent with EC measurements but with different accuracies among footprint algorithms. At US-Bes in September 2013, RMSE and NNSE were 0.002 μmol m−2 s−1 and 0.782 using the DF algorithm, but 0.007 μmol m−2 s−1 and 0.758 using HF and 0.007 μmol m−2 s−1 and 0.765 using GF, respectively. DF algorithm performed better than the HF and GF algorithms in capturing the temporal variation in daily CH4 flux each month, while the model accuracy was similar among the three algorithms due to flat landscapes. Temporal variations in CH4 flux during 2013–2015 were predominately explained by air temperature (67–74%), followed by precipitation (22–36%). Spatial heterogeneities in vegetation fraction and elevation dominated the spatial variations in CH4 flux for all five tower domains despite relatively weak differences in simulated CH4 flux among three footprint algorithms. The CLM-Microbe model can simulate CH4 flux at both plot and landscape scales at a high temporal resolution, which should be applied to other landscapes. Integrating land surface models with an appropriate algorithm provides a powerful tool for upscaling CH4 flux in terrestrial ecosystems.

Fumonisin B1 (FB1) is a major fusarium mycotoxin that largely contaminates feedstuffs and foods, posing a health risk to both animals and humans. This mycotoxin can enter the human body directly through contaminated food consumption or indirectly by toxins and their metabolites. In a prior study, feed-borne FB1 is one of the leading mycotoxins in breeder eggs, leading to reduced hatchability and gizzard ulceration in chicken progenies. Currently, no effective way is available to remove FB1 from feeds and human-contaminated foods. We hypothesize that FB1 can be reduced to low risk by protocatechuic acid (PCA). To assess the ability of FB1 to be degraded in vivo, 1 ppm of FB1 was treated with PCA, or D-glucose, or silymarin, or anti-FB1 monoclonal antibody. Our study revealed that both D-glucose and PCA exhibited 53.4 and 71.43% degradation, respectively, at 80°C for 2 h, while 35.15% of FB1 detoxification was determined in the silymarin group at 60°C for 0.5 h. A dose-dependent manner was found after treatment with D-glucose or PCA at 80°C for 2 h. As for detoxification of anti-FB1 monoclonal antibody, the 1:3,000 dilution induced significant FB1 detoxification, accounting for 25.9% degradation at 25°C for 2 h. Furthermore, 50 SPF 11-day-old embryonated eggs were divided into 10 groups, with five eggs per group. Post treatment with PCA or D-glucose, or silymarin or anti-FB1 monoclonal antibody, the treated samples were inoculated into albumens and monitored daily until the hatching day. Consequently, 100% of the chickens survived in the D-glucose group and other control groups, except for the FB1 control group, while 80, 80, and 60% hatching rates were found in the PCA-treated group, the anti-FB1 monoclonal antibody-treated group, and the silymarin-treated group. Additionally, both the FB1 group and the silymarin-treated group yielded lower embryo growth than other groups did. Postmortem, lower gizzard ulceration index was determined in the PCA-treated group and the anti-FB1 monoclonal antibody-treated group compared to those of the silymarin-treated group and D-glucose-treated group. Based on the above evidence, PCA is a promising detoxification to reduce FB1 contamination in the poultry industry, contributing to the eradication of mycotoxin residuals in the food chain and maintaining food security for human beings.

In this study, the exopolysaccharide (EPS) from Lactiplantibacillus plantarum (HMX2) was isolated from Chinese Northeast Sauerkraut. Its effects on juvenile turbot were investigated by adding different concentrations of HMX2-EPS (C: 0 mg/kg, H1: 100 mg/kg, H2: 500 mg/kg) to the feed. Compared with the control group, HMX2-EPS significantly improved the growth performance of juvenile turbot. The activities of antioxidant enzymes, digestive enzymes, and immune-related enzymes were significantly increased. HMX2-EPS could also increase the secretion of inflammatory factors and enhance the immune response of turbot by regulating the IFN signal transduction pathway and exhibit stronger survival rates after the A. hydrophila challenge. Moreover, HMX2-EPS could improve the diversity of intestinal microbiota in juvenile fish, increase the abundance of potential probiotics, and reduce the abundance of pathogenic bacteria. The function of gut microbes in metabolism and the immune system could also be improved. All results showed better effects with high concentrations of HMX2-EPS. These results indicated that HMX2-EPS supplementation in the diet could promote growth, improve antioxidant activity, digestive capacity, and immunity capacity, and actively regulate the intestinal microbiota of juvenile turbot. In conclusion, this study might provide basic technical and scientific support for the application of L. plantarum in aquatic feed.

Abstract Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus that causes the disease melioidosis. B. pseudomallei expresses a number of proteins that contribute to its intracellular survival in the mammalian host. We previously demonstrated that immunization with OMVs derived from B. pseudomallei grown in nutrient-rich media protects mice against lethal disease. Here, we evaluated if OMVs derived from B. pseudomallei grown under macrophage-mimicking growth conditions could be enriched with intracellular-stage proteins in order to improve the vaccine. We show that OMVs produced in this manner (M9 OMVs) contain proteins associated with intracellular survival yet are non-toxic to living cells. Immunization of mice provides significant protection against pulmonary infection similar to that achieved with a live attenuated vaccine and is associated with increased IgG, CD4+, and CD8+ T cells. OMVs possess inherent adjuvanticity and drive DC activation and maturation. These results indicate that M9 OMVs constitute a new promising vaccine against melioidosis.

A series of new 1,4-pentadien-3-one derivatives containing 1,2,4-triazole moiety were synthesized. The structures of the synthesized compounds were charactered via 1H NMR, 13C NMR and HRMS. Antibacterial bioassays indicated that some of compounds showed potential antibacterial activities against Ralstonia solanacearum (Rs), Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri (Xac). Compounds F8 and F17 showed good in vitro antibacterial activities against Rs, with the EC50 values of 18.6 and 18.6 μg/mL, respectively, which were better than commercial agent bismerthiazol (55.2 μg/mL). Furthermore, compounds F12 and F15 showed good in vitro antibacterial activities against Xoo, with the EC50 values of 10.9 and 17.5 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Moreover, compounds F2, F9, F16 and F17 showed good in vitro antibacterial activities against Xac, with the EC50 values of 6.6, 5.4, 7.5 and 7.8 μg/mL, respectively, which were better than commercial agent bismerthiazol (54.9 μg/mL). The effect of compound F9 on Xac bacterial cell membrane rupture was observed by scanning electron microscopy (SEM). In addition, antiviral bioassays indicated that some of compounds showed excellent protection activities against tobacco mosaic virus (TMV). Compounds F5 and F15 showed good protecting activity against TMV, with the EC50 values of 108.3 and 105.4 μg/mL, respectively, which were better than commercial agent ningnanmycin (214.7 μg/mL). Microscale thermophoresis (MST) also showed that the binding of compound F2 to TMV coat protein (TMV-CP) yielded a Kd value of 1.260 ± 0.654 μmol/L, which was very close to ningnanmycin (1.058 ± 0.286 μmol/L). Similarly, the molecular docking studies for F2 and F5 with TMV-CP (PDB code: 1EI7, ID: 4QGH) indicated that compounds F2 and F5 had partially interacted with TMV-CP.

During atmospheric plasma spraying, a cooling process usually plays an important role in the coating quality, especially for the oxidation containment of metallic coatings. CuNiIn and Mo coatings were prepared using atmospheric plasma spraying with different cooling processes. The obtained coatings were characterized in terms of microstructure, microhardness and tensile strengths. The relation between the coating microstructure and their fretting fatigue behavior was emphasized. The results show that the sensitivity of Mo coatings to the cooling process is lower than CuNiIn coatings. The resistance to fretting fatigue is determined by the coating microhardness, correlated with the contents of oxides and pores. The fretting wear mechanisms of both the coatings are galling, third body abrasive wear and material transfer.

Abstract Background Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM. Results Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression. Conclusions Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.

Abstract Background There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such “functional metabolites” in ARDS using metabolomics and in vivo experiments in a mouse model. Methods Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for “functional metabolites”, which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of “functional metabolites” in the lung injury and mortality caused by the respiratory disorder. Results The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. Conclusion Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. Trial registration Chinese Clinical Trial Registry, ChiCTR1800015930 . Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4

The present study proposes a time domain model for the Vortex-induced Vibration (VIV) simulation of a catenary riser under the combination of the current and oscillatory flow induced by vessel motion. In this model, the hydrodynamic force of VIV comprises excitation force, hydrodynamic damping and added mass, which are taken as functions of the non-dimensional frequency and amplitude ratio. The non-dimensional frequency is related with the response frequency, natural frequency, lock-in range and the fluid velocity. The relatively oscillatory flow induced by vessel motion is taken into account in the fluid velocity. Considering that the added mass coefficient and the non-dimensional frequency can affect each other, an iterative analysis is conducted at each time step to update the added mass coefficient and the natural frequency. This model is in detail validated against the published test models. The results show that the model can reasonably reflect the effect of the added mass coefficient on the VIV, and can well predict the riser’s VIV under stationary and oscillatory flow induced by vessel motion. Based on the model, this study carries out the VIV simulation of a catenary riser with harmonic vessel motion. By analyzing the bending moment near the touchdown point, it is found that under the combination of the ocean current and oscillatory flow the vessel motion may decrease the VIV response, while increase the excited frequencies. In addition, the decreasing rate of the VIV under vessel surge is larger than that under vessel heave at small vessel motion velocity, while the situation becomes opposite at large vessel motion velocity.