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Abstract Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079–0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT

The pipe curtain structure method (PSM) is a novel construction method to control ground deformation strictly. Compared with the traditional pipe-roofing and pipe jacking method, the connection between pipes in large spacings using PSM is widely acknowledged as a unique construction procedure. Further study on this connection procedure is needed to resolve similar cases in that the pipes are inevitably constructed on both sides of existing piles. Cutting the steel plate during the connection procedure is the first step, which is crucial to control the safety and stability of the surrounding environment and existing structures. The deformation mechanism and limit support pressure of the cutting steel plate during the connection between pipes in large spacings are studied in this paper, relying on the undercrossing Yifeng gate tower project of Jianning West Road River Crossing Channel in Nanjing, China. A modified 3D wedge-prism failure model is proposed using the 3D discrete element method. Combined with Terzaghi loose earth pressure theory and the limit equilibrium theory, the analytical solutions for the limit support pressure of the excavation face of the cutting steel plate are derived. The modified 3D wedge-prism failure model and corresponding analytical solutions are categorised into two cases: (a) unilateral cutting scheme, and (b) bilateral cutting scheme. The analytical solutions for the two cases are verified from the numerical simulation and in-situ data and compared with the previous solutions. The comparative analysis between the unilateral and bilateral cutting schemes indicates that the bilateral cutting scheme can be adopted as a priority. The bilateral cutting scheme saves more time and induces less ground deformation than the unilateral one due to the resistance generated from the superimposed wedge. In addition, the parametric sensitivity analysis is carried out using an orthogonal experimental design. The main influencing factors arranged from high to low are the pipe spacing, the cutting size, and the pipe burial depth. The ground deformation increases with the increased cutting size and pipe spacing. The pipe burial depth slightly affects the ground deformation if the other two factors are minor. Cutting steel plates in small sizes, excavating soil under low disturbance, and supporting pipes for high frequency can effectively reduce the ground surface subsidence.

The Shigang Oilfield in the Subei Basin is characterized by low-porosity and ultra-low permeability sandstone reservoirs. The natural productivity of the oil wells is low, but hydraulic fracturing followed by water injection can improve oil production capacity. However, during the development of the oilfield, problems such as low oil recovery rates, low recovery factors, and poor development effectiveness have become apparent, exacerbating development challenges. Therefore, it is necessary to identify the reasons for inefficient development and explore strategies to enhance recovery, providing a theoretical basis for improving the development effectiveness of the Shigang Oilfield. Using methods such as whole-rock mineral composition analysis, gas-measured core porosity and permeability parameters, and core sensitivity evaluation, the micro characteristics of the reservoir were analyzed in terms of rock mineral composition, pore-throat structure, and rock sensitivity. Numerical reservoir simulations and laboratory core experiments were conducted to study the distribution characteristics of residual oil after fracturing water flooding. Strategies to enhance oil recovery were investigated through nuclear magnetic resonance online displacement experiments. The results showed that the reservoir cores exhibited typical low-porosity and ultra-low permeability characteristics, with certain velocity sensitivity and water sensitivity during development. After fracturing water flooding, residual oil in the cores was mainly distributed in pore channels with diameters ranging from 0.01 to 1 μm. The use of surfactant flooding and secondary water flooding increased the recovery rate of residual oil in the cores by 14.81%. The main reasons for inefficient development included ultra-low reservoir permeability, the development of micro pores and micro fractures, and sensitivity to velocity and water. Water injection development could cause rock mineral swelling and migration, increasing flow resistance. Therefore, after fracturing water flooding, only the recovery of residual oil along the main flow paths was significantly improved, with the overall utilization degree remaining low, and a considerable amount of residual oil still concentrated in the reservoir. It is recommended to use chemical flooding and multiple rounds of displacement to enhance the utilization of oil in medium and small pore channels, further improving the development effectiveness of the oilfield.

Abstract FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Selenium (Se), is an essential trace element in the diet of fish and aquatic animals needed for growth, thyroid hormone metabolism, antioxidant activity, and immunity. Thus, this study has evaluated the dietary selenium yeast (Se-yeast) impact on the growth performance, antioxidant capacity, and gut bacterial community of zebrafish, Danio rerio. The fish with an average weight of 0.247 g ± 0.005 were distributed in 12 glass aquariums. 30 fish per aquarium in three replicates per group were exposed to different dietary Se-yeast concentrations: 0.3 mg/kg (control), 0 mg/kg, 3 mg/kg, and 30 mg/kg for three weeks. The result indicated a higher body weight gain and specific growth rate in the 3 mg/kg group in all groups. Se significantly accumulated in the liver, muscle, gill, and gut. The antioxidant genes superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx1), and the gut marker genes: solute carrier family 15 member 1b (slc15a1b), fatty acid binding protein 2 (fabp2), cytochrome P450 family 8 subfamily B member 1 (cyp8b1), and cytochrome P450 family 3 subfamily A, polypeptide 65 (cyp3a65) were significantly expressed in the gut tissue. The 16 s rRNA sequencing showed a significant difference at phyla Proteobacteria, Fusobacteria, Firmicutes, and Actinobacteria and Cetobacterium, Aeromonas, mycobacterium, and Lactobacillus at the genus level. It was concluded that dietary Se 3 mg/kg can promote growth performance and antioxidant status, furthermore, dietary Se yeast has a significant impact on the gut microbiota of D. rerio.

BackgroundThe inflammatory response holds paramount significance in the context of intracerebral hemorrhage (ICH) and exhibits a robust correlation with mortality rates. Biological markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI) play crucial roles in influencing the systemic inflammatory response following ICH. This study aims to compare the predictive efficacy of NLR, PLR, LMR, SII, and SIRI concerning the risk of mortality in the intensive care unit (ICU) among critically ill patients with ICH. Such a comparison seeks to elucidate their early warning capabilities in the management and treatment of ICH.MethodsPatients with severe ICH requiring admission to the ICU were screened from the Medical Information Marketplace for Intensive Care (MIMIC-IV) database. The outcomes studied included ICU mortality and 30 day ICU hospitalization rates, based on tertiles of the NLR index level. To explore the relationship between the NLR index and clinical outcomes in critically ill patients with ICH, we utilized receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and multivariate logistic regression analysis.ResultsA total of 869 patients (51.9% male) were included in the study, with an ICU mortality rate of 22.9% and a 30 day ICU hospitalization rate of 98.4%. Among the five indicators examined, both the ROC curve and DCA indicated that NLR (AUC: 0.660, 95%CI: 0.617–0.703) had the highest predictive ability for ICU mortality. Moreover, this association remained significant even after adjusting for other confounding factors during multivariate analysis (HR: 3.520, 95%CI: 2.039–6.077). Based on the results of the multivariate analysis, incorporating age, albumin, lactic acid, NLR, and GCS score as variables, we developed a nomogram to predict ICU mortality in critically ill patients with ICH.ConclusionNLR emerges as the most effective predictor of ICU mortality risk among critically ill patients grappling with ICH when compared to the other four indicators. Furthermore, the integration of albumin and lactic acid indicators into the NLR nomogram enhances the ability to promptly identify ICU mortality in individuals facing severe ICH.

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

Intracerebral hemorrhage (ICH) stands as a prevalent and pivotal clinical condition. The potential cooccurrence of acute kidney injury (AKI) among afflicted individuals can profoundly influence their prognosis. In recent times, there has been a growing focus among clinical practitioners on researching the relationship between ICH and AKI. AKI occurring concurrently with ICH predominantly arises from both hemodynamic and non-hemodynamic mechanisms. The latter encompasses neurohumoral regulation, inflammatory response, oxidative stress, and iatrogenic factors such as contrast agents, dehydrating agents, antibiotics, and diuretics. Moreover, advanced age, hypertension, elevated baseline creatinine levels, chronic kidney disease, and larger hematomas predispose patients to AKI. Additionally, the current utilization of biomarkers and the development of predictive models appear promising in identifying patients at risk of AKI after ICH. This article aims to underscore the potential of the aforementioned insights to inspire novel approaches to early clinical intervention.

PurposeThe ratio of monocyte to high-density lipoprotein cholesterol (MHR) has surfaced as a novel biomarker indicative of inflammation and oxidative stress. The aim of our study was to evaluate the association between MHR and the risk of kidney stones.MethodsThis study analyzed data from individuals aged 20-79 who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The MHR was assessed as the exposure variable, while a self-reported history of kidney stones was used as the outcome variable. The independent relationship between MHR and the risk of kidney stones was thoroughly evaluated.ResultsThis study included 28,878 participants, and as the quartile range of the MHR increased, the proportion of kidney stones also rose progressively (7.20% to 8.89% to 10.88% to 12.05%, P

Abstract Phenolic compounds are industrially versatile chemicals, also the most ubiquitous pollutants. Recently, biosynthesis and biodegradation of phenols has attracted increasing attention, while phenols’ toxicity is a major issue. Here, we evolved phloroglucinol-tolerant Escherichia coli strains via adaptive evolution, and three mutations (ΔsodB, ΔclpX and fetAB overexpression) prove of great assistance in the tolerance improvement. We discover that phloroglucinol complexes with iron and promotes the generation of hydroxyl radicals in Fenton reaction, which leads to reducing power depletion, lipid peroxidation, and ferroptosis-like cell death of E. coli. Besides phloroglucinol, various phenols can trigger ferroptosis-like death in diverse organisms, from bacteria to mammalian cells. Furthermore, repressing this ferroptosis-like death improves phloroglucinol production and phenol degradation by corresponding strains respectively, showing great application potential in microbial degradation or production of desired phenolic compounds, and phloroglucinol-induced ferroptosis suppresses tumor growth in mice, indicating phloroglucinol as a promising drug for cancer treatment.

Due to stringent aircraft safety requirements and the high cost of experiments, there is a scarcity of failure samples, which creates a gap between existing diagnostic models and practical applications. To address this issue, we have developed a small-sample civil aircraft fault diagnosis method. This method combines a meta-learning approach to tackle data imbalance with a channel attention mechanism to enhance feature extraction efficiency. Specifically, our approach integrates the advantages of meta-learning and attention regularization, effectively addressing both the imbalance in training sample distribution and the need for human interaction to enhance feature representation. We then evaluated five data imbalances and introduced a fault diagnosis algorithm based on a one-dimensional convolutional network, which has been successfully applied to solve small sample yield tasks in two datasets. Additionally, we provide baseline accuracy under the same conditions for comprehensive comparison and reference. Through extensive experiments, our method achieves competitive performance and demonstrates its superiority in solving imbalanced distribution experimental configurations.

Abstract This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (ntotal = 452). In Cohort 1 (n = 83), task-based functional magnetic resonance imaging (t-fMRI) results from a region-of-interest (ROI) analysis revealed no direct correlation between amygdala reactivity to fearful and angry faces and GPT. Instead, whole-brain analyses revealed GPT to robustly negatively vary with activations in the right ventromedial prefrontal cortex (vmPFC), supramarginal gyrus, and angular gyrus in the contrast of fearful + angry faces > shapes. Moreover, task-based psychophysiological interaction (PPI) analyses showed that the high GPT group showed weaker functional connectivity of the vmPFC seed with a top-down control network and visual pathways when processing fearful or angry faces compared to their lower GPT counterparts. In Cohort 2, resting-state functional connectivity (rs-FC) analyses indicated stronger connectivity between the vmPFC seed and the top-down control network and visual pathways in individuals with higher GPT. Comparing the two cohorts, bilateral amygdala seeds showed weaker associations with the top-down control network in the high group via PPI analyses in Cohort 1. Yet, they exhibited distinct rs-FC patterns in Cohort 2 (e.g., positive associations of GPT with the left amygdala-top-down network FC but negative associations with the right amygdala-visual pathway FC). The study underscores the role of the vmPFC and its functional connectivity in understanding GPT, rather than amygdala reactivity.

Abstract Glioma is the most common primary malignant brain tumor in adults and remains an incurable disease at present. Thus, there is an urgent need for progress in finding novel molecular mechanisms that control the progression of glioma which could be used as therapeutic targets for glioma patients. The RNA binding protein cytoplasmic polyadenylate element-binding protein 2 (CPEB2) is involved in the pathogenesis of several tumors. However, the role of CPEB2 in glioma progression is unknown. In this study, the functional characterization of the role and molecular mechanism of CPEB2 in glioma were examined using a series of biological and cellular approaches in vitro and in vivo. Our work shows CPEB2 is significantly downregulated in various glioma patient cohorts. Functional characterization of CPEB2 by overexpression and knockdown revealed that it inhibits glioma cell proliferation and promotes apoptosis. CPEB2 exerts an anti-tumor effect by increasing p21 mRNA stability and inducing G1 cell cycle arrest in glioma. Overall, this work stands as the first report of CPEB2 downregulation and involvement in glioma pathogenesis, and identifies CPEB2 as an important tumor suppressor gene through targeting p21 in glioma, which revealed that CPEB2 may become a promising predictive biomarker for prognosis in glioma patients.

Abstract Lung cancer is the leading cause of cancer-related death. Lysosomes are key degradative compartments that maintain protein homeostasis. In current study, we aimed to construct a lysosomes-related genes signature to predict the overall survival (OS) of patients with Lung Adenocarcinoma (LUAD). Differentially expressed lysosomes-related genes (DELYs) were analyzed using The Cancer Genome Atlas (TCGA-LUAD cohort) database. The prognostic risk signature was identified by Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression and multivariate Cox analysis. The predictive performance of the signature was assessed by Kaplan–Meier curves and Time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the potential molecular biological function and signaling pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) were applied to estimate the difference of tumor microenvironment (TME) between the different risk subtypes. An eight prognostic genes (ACAP3, ATP8B3, BTK, CAV2, CDK5R1, GRIA1, PCSK9, and PLA2G3) signature was identified and divided patients into high-risk and low-risk groups. The prognostic signature was an independent prognostic factor for OS (HR > 1, p

Solar-induced chlorophyll fluorescence (SIF) is strongly physiologically associated with vegetation photosynthesis, and has been broadly employed to monitor gross primary productivity (GPP). However, for some understudied ecosystems, such as the alpine grasslands of the Tibetan Plateau (TP), it is highly uncertain about how SIF performs in tracking GPP. Here, by collecting eddy covariance-derived GPP and climatic data at four grassland sites in the TP, the performances of remotely sensed SIF products (CSIF and GOSIF) in estimating GPP at different time scales (8-day, monthly and growing season) were evaluated and compared against reflectance-based greenness vegetation indices (GVIs) and photochemical reflectance indices (PRIs). Moreover, the SIF-GPP relationship was further examined under different water conditions. The results showed that SIF performed best in tracking GPP variations at all temporal scales compared with GVIs and PRIs. With temporal aggregation, the SIF-GPP relationship was markedly enhanced. We further found that both determination coefficient (R2) values and slopes of the SIF-GPP relationship tended to be lower with decreasing soil water content or increasing vapor pressure deficit. This indicates SIF and GPP will be decoupled with aggravating water stress and their relationship is not universal under different water conditions. Morever, integrating soil water content with SIF improved GPP estimation, underscoring the vital role of water availability in influencing the SIF-GPP relationship. This study can boost our understanding on the variant SIF-GPP relationship and suggests that the regulation effect of water availability need be considered to improve the SIF-derived GPP estimation.

Background: Brain abscesses caused by Nocardia are rare and difficult to diagnose. Nocardia farcinica is among the most common species; however, the conventional diagnosis of N. farcinica infection consists of cerebrospinal fluid (CSF) and blood culture and Gram staining. These procedures prolong the time to diagnosis and initiating treatment. Case presentation: A 69-year-old woman with diabetes mellitus presented with headaches and dizziness persisting for 2 weeks, which was initially diagnosed as a brain abscess. Due to the unusual presentation and rapid progression of symptoms, she underwent surgical resection of the brain abscess. No pathogens were detected in blood or CSF cultures. However, metagenomic next-generation sequencing (mNGS) identified N. farcinica and Torque teno virus in pus extracted from the abscesses. The patient received appropriate antibiotic therapy and recovered fully without any residual neurological deficits. Conclusion: mNGS useful for prompt diagnosis and selection of antibiotic therapy for brain abscesses caused by Nocardia. Surgical intervention is necessary in some cases.

Abstract This study investigated the orbital morphological features that lead to fractures at different sites by comparing patients with isolated inferior wall fracture (IWF) to patients with isolated medial wall fracture (MWF). This study analyzed the orbital morphologic characteristics of all orbital fracture patients who underwent orbital computed tomography (CT) scans between January 2017 and October 2022. On CT scans, the bony structures of the orbit were measured. We investigated the bilateral symmetry of orbital. In addition, orbital morphological differences were compared between patients with fractures of the medial wall and those with fractures of the inferior wall. A total of 135 patients with orbital fractures were included in the study. Of these, 91 were isolated MWFs and 44 were isolated IWF. We confirmed the symmetry of bilateral orbits and measured the orbit of the uninjured side. No differences were found between the MWF group and the IWF group in terms of ocular prominence, horizontal orbital diameter, orbital rim angle, sagittal orbital depth, sagittal orbital depth, and angle of inferior wall inclination. The distance between the infraorbital nerve (ION) entry point and the orbital rim was significantly smaller in the inferior lateral wall fracture group than in the MWF group (11.87 ± 2.54 vs 14.90 ± 4.64, P

Abstract How the soil bacterial communities vary with elevation is context-dependent, and the effect of soil translocation between elevations on bacterial community structure and metabolic function was not fully understood yet. Here, the bacterial community composition and diversity at five elevations along a 1600–3000 m elevation gradient on a mountainside in northwest Sichuan were characterized, and the responses of soil bacterial community to simulated climate changes were further studied by soil translocation reciprocally at three elevations for 12 months. Significant differences were found in soil temperature and moisture at different elevations, but there was no observed change in bacterial alpha diversity. The relative abundance of bacterial phyla was significantly different among the five elevations except for Proteobacteria (the dominant bacterial phyla in five elevation), and most bacterial phyla correlated with soil temperature, moisture, pH and soil bulk density. The direct effect of soil properties (pH, soil nutrients and soil bulk density) on soil bacterial community was stronger than the direct effect of temperature and moisture. Soil translocation changed the relative abundance of some bacterial phyla, and taxonomic groups with significant changes were mainly non-dominant phyla rather than the dominant phyla. Metabolism was the primary function of bacterial community at all elevations, which accounted for ~ 80% of relative abundance, and soil translocation had little effect on metabolic function. These findings indicated that soil bacterial dominant taxa and soil bacterial metabolic functions are relatively stable, which contribute to the stability of the ecosystem when response to the climate change in the future.

Abstract Graves ophthalmopathy (GO) patients often undergo retrobulbar injection of glucocorticoids (GCs) as a common therapeutic approach. This study aimed to explore the impact of various patterns of extraocular muscle (EOM) enlargement on EOM changes following retrobulbar GCs injection in patients with GO. A retrospective analysis was conducted on GO patients who underwent retrobulbar GCs injections. Data pertaining to EOM diameter (EMD) and muscle diameter index (MDI) were collected from orbital computed tomography (CT) scans. The MDI change (ΔMDI) was calculated by comparing pre- and post-injection MDI values. The relationship between each pre EMD/MDI and ΔMDI was assessed using univariate and multivariate logistic regression analysis. A total of 68 patients with GO were included in this study, accounting for 118 eyes. After retrobulbar injections of GCs, 84 eyes showed a decrease in the MDI, while 34 eyes exhibited an increase in MDI. A threshold effect was observed in the relationship between medial pre EMD/MDI and ΔMDI. When the medial pre EMD/MDI was less than 0.28, a higher medial pre EMD/MDI was associated with a smaller ΔMDI (β = − 25.21, p = 0.0175). However, when the medial pre EMD/MDI was greater than 0.28, no significant association was found between pre EMD/MDI and ΔMDI. There was a negative correlation between medial + lateral pre EMD/MDI and ΔMDI (β = − 11.76, p

The performance of heat exchangers in the pressurized water test loop is a critical factor in ensuring the achievement of irradiation parameters for fuel assemblies and the safety of experimental operations. The effect of the heat exchange area margin on the heat exchangers in the pressurized water test loop for the fuel assembly during the steady-state irradiation is analyzed. Additionally, optimization methods for determining the margin of heat exchange area and corresponding design strategies are further investigated. It shows that the effect of the heat exchange area margin on the heat exchange power is less affected by the inlet temperature of the primary water and is primarily influenced by the flow rate of the primary water. A decrease in the flow rate of the primary water reduces the compensatory effect of the cooling section on power and enhances the weakening effect of the regeneration section on power. Meanwhile, the correspondence between the margin of the regeneration section and the cooling section, established based on design conditions, can be applicable when there are changes in the inlet temperature of the primary water, but it is not suitable when there are changes in the flow rate of the primary water. When the flow rate of the primary water decreases, the cooling section margin required to compensate for the decrease in power caused by the regeneration section margin will increase significantly. In addition, short-circuiting the heat exchange tubes in the regeneration section can effectively enhance the heat transfer capability. Furthermore, setting the heat exchange area margins of the regeneration and cooling sections to zero can serve as a termination condition for iterative calculations in the verification of regenerative heat exchangers under off-design conditions.

d-Lactic acid serves as a pivotal platform chemical in the production of poly d-lactic acid (PDLA) and other value-added products. This compound can be synthesized by certain bacteria, including Klebsiella pneumoniae. However, industrial-scale lactic acid production in Klebsiella pneumoniae faces challenges due to growth inhibition caused by lactic acid stress, which acts as a bottleneck in commercial microbial fermentation processes. To address this, we employed a combination of evolutionary and genetic engineering approaches to create an improved Klebsiella pneumoniae strain with enhanced lactic acid tolerance and production. In flask fermentation experiments, the engineered strain achieved an impressive accumulation of 19.56 g/L d-lactic acid, representing the highest production yield observed in Klebsiella pneumoniae to date. Consequently, this strain holds significant promise for applications in industrial bioprocessing. Notably, our genome sequencing and experimental analyses revealed a novel correlation between UTP-glucose-1-phosphate uridylyltransferase GalU and lactic acid resistance in Klebsiella pneumoniae. Further research is warranted to explore the potential of targeting GalU for enhancing d-lactic acid production.

Abstract In microbial cell factory, CO2 release during acetyl-CoA production from pyruvate significantly decreases the carbon atom economy. Here, we construct and optimize a synthetic carbon conserving pathway named as Sedoheptulose-1,7-bisphosphatase Cycle with Trifunctional PhosphoKetolase (SCTPK) in Escherichia coli. This cycle relies on a generalist phosphoketolase Xfspk and converts glucose into the stoichiometric amounts of acetylphosphate (AcP). Furthermore, genetic circuits responding to AcP positively or negatively are created. Together with SCTPK, they constitute a gene-metabolic oscillator that regulates Xfspk and enzymes converting AcP into valuable chemicals in response to intracellular AcP level autonomously, allocating metabolic flux rationally and improving the carbon atom economy of bioconversion process. Using this synthetic machinery, mevalonate is produced with a yield higher than its native theoretical yield, and the highest titer and yield of 3-hydroxypropionate via malonyl-CoA pathway are achieved. This study provides a strategy for improving the carbon yield of microbial cell factories.

Automatic Identification System (AIS) can obtain a large amount of data on ship trajectories and movement characteristics, which provides data support for ship route planning, navigation safety, and maritime traffic control. Therefore, it is of great importance to analyze and cluster the AIS data to obtain an understanding of the movement behavior of ships. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is capable of discovering arbitrarily shaped clusters and is suitable for clustering ship trajectories. However, the traditional DBSCAN algorithm suffers from the following shortcomings. First, the DBSCAN algorithm requires the input of a similarity matrix between the trajectories, and the similarity matrix obtained from the traditional Hausdorff distances does not identify the trajectory directions. Second, the DBSCAN algorithm is sensitive to the input parameters, and the clustering results obtained from different datasets with the same parameters vary widely. Finally, the DBSCAN algorithm is poor at clustering multi-density distribution datasets. To address these shortcomings, this study proposes a multi-density adaptive trajectory clustering (MDA-Traclus) algorithm, which considers the multi-density distribution trajectory dataset, adaptively determines the input parameters, and adds a trajectory direction identification mechanism to realize the clustering of trajectory clusters with different directions and different densities. Here, the classical DBSCAN algorithm, KANN-DBSCAN algorithm, and MDA-Traclus algorithm are compared and analyzed using four manually labeled trajectory datasets and a real trajectory dataset. The results show that the MDA-Traclus algorithm and KANN-DBSCAN algorithm are able to automatically determine the input parameters when clustering trajectory datasets with uniformly distributed densities and achieve the same clustering effect as the DBSCAN algorithm. When the trajectory density distribution is not uniform and the directions of the trajectory clusters are not consistent, the MDA-Traclus algorithm can effectively identify the low-density regions, differentiate the different directions of trajectories, and improve the clustering of the trajectories.

Light is one of the most important environmental factors for plant growth. In the production process of tung oil tree cultivation, due to the inappropriate growth of shading conditions, the lower branches are often dry and dead, which seriously affects the yield of tung oil trees. However, little is known about the key factors of light-induced tree photomorphogenesis. In this study, a total of 22 VfBBX family members were identified to provide a reference for candidate genes in tung tree seedlings. All members of the VfBBX family have different numbers of highly conserved B-box domains or CCT domains. Phylogenetic evolution clustered the VfBBX genes into four categories, and the highest density of members was on chromosome 6. Interspecific collinearity analysis suggested that there were six pairs of duplicate genes in VfBBX members, but the expression levels of all family members in different growth and development stages of the tung tree were significantly divergent. After different degrees of shading treatment and physiological data determination of tung tree seedlings, the differential expression level and chlorophyll synthesis genes correlation analysis revealed that VfBBX9 was a typical candidate nuclear localization transcription factor that was significantly differentially expressed in light response. This study systematically identified the VfBBX gene family and provided a reference for studying its molecular function, enhanced the theoretical basis for tung tree breeding, and identified excellent varieties.

In recent years, laser scanners integrated with Unmanned Aerial Vehicles (UAVs) have exhibited great potential in conducting power line inspections in harsh environments. The point clouds collected for power line inspections have numerous advantages over remote image data. However, point cloud-based individual power line extraction, which is a crucial technology required for power line inspections, still poses several challenges such as massive 3D points, imbalanced category points, etc. Moreover, in various power line scenarios, previous studies often require manual setup and careful adjustment of different thresholds to separate different power lines, which is inefficient for practical applications. To handle these challenges, in this paper, we propose a multi-branch network to automatically extract an arbitrary number of individual power lines from point clouds collected by UAV-based laser scanners. Specifically, to handle the massive 3D point clouds in complex outdoor scenarios, we propose to leverage deep neural network for efficient and rapid feature extraction in large-scale point clouds. To mitigate imbalanced data quantities across different categories, we propose to design a weighted cross-entropy loss function to measure the varying importance of each category. To achieve the effective extraction of an arbitrary number of power lines, we propose leveraging a loss function to learn the discriminative features that can differentiate the points belonging to different power lines. Once the discriminative features are learned, the Mean Shift method can distinguish the individual power lines by clustering without supervision. The evaluations are executed on two datasets, which are acquired at different locations with UAV-mounted laser scanners. The proposed method has been thoroughly tested and evaluated, and the results and discussions confirm its outstanding ability to extract an arbitrary number of individual power lines in point clouds.

IntroductionRock weathering is crucial in the development of soil. Yet the role of bacteria in the fine particle-forming process of purple mudstone is not fully understood, especially under nitrogen fertilization.MethodsIn this study, the particles (0.25 mm to 1 mm) of purple mudstone from Penglai Group (J3p) were selected as the test material. Two nitrogen fertilizers, i.e., urea (U) and ammonium bicarbonate (AB), and four application levels (0, 280, 560, and 840 N kg∙ha−1) with 18 replications were designed in an incubation experiment. The weathering indices and bacterial community structure of the purple mudstone particles were investigated after 120 days of incubation.ResultsThe results showed that the weathering indices of purple mudstone particles in the AB treatment were higher than that in the U treatment at the same fertilization levels and a reducing trend was observed with increasing nitrogen fertilizer levels under the same nitrogen fertilizer application types. The diversities of the bacterial community were extremely significantly altered by nitrogen fertilizer application (p

Abstract Satellite communication, especially low earth orbit satellites, an important part of the space‐air‐ground integrated network, is a promising solution to support global coverage and reliable communication. However, the originally connected links will be off, when the satellites move into polar regions. In addition, the condition of the path broken will dramatically increase with the number of satellites increasing. Thus, it is a continually considerable challenge to design an efficient and stationary routing algorithm for intra‐satellites. This paper presents a waypoint segment routing algorithm to realise persistent routes when the satellites move into polar regions. The waypoint selection problem is modelled and solved in stages. One of the source‐based routing algorithms, segment routing, is applied in low earth orbit satellite network to provide stable, efficient and reliable packets forwarding. By adding the selected waypoints into the segment list of the segment routing, the next‐snapshot broken links can be avoided. Based on the proposed waypoint segment routing algorithm, the problem of the path broken can be effectively solved. By comparing the packet loss, the delay and the delay jitter of the satellite simulation networks, the proposed algorithm is preferable to the popular optimised link‐state routing algorithm for the satellite mega‐constellation networks.

The warming-wetting climates in Chinese drylands, together with a series of ecological engineering projects, had caused apparent changes to vegetation therein. Regarding the vegetation greening trend, different remote sensing data had yielded distinct findings. It was critical to evaluate vegetation dynamics in Chinese drylands using a series of remote sensing data. By comparing the three most commonly used remote sensing datasets [i.e., MODIS, Advanced Very High Resolution Radiometer (AVHRR), and Landsat], this study comprehensively investigated vegetation dynamics for Chinse drylands. All three remote sensing datasets exhibited evident vegetation greening trends from 2000 to 2020 in Chinese drylands, especially in the Loess Plateau and Northeast China. However, Landsat identified the largest greening areas (89.8%), while AVHRR identified the smallest greening area (58%). The vegetation greening areas identified by Landsat comprise more small patches than those identified by MODIS and AVHRR. The MODIS data exhibited a higher consistency with Landsat than with AVHRR in terms of detecting vegetation greening areas. The three datasets exhibited high consistency in identifying vegetation greening in Northeast China, Loess Plateau, and Xinjiang. The percentage of inconsistent areas among the three datasets was 39.56%. The vegetation greening areas identified by Landsat comprised more small patches. Sensors and the atmospheric effect are the two main reasons responsible for the different outputs from each NDVI product. Ecological engineering projects had a great promotion effect on vegetation greening, which can be detected by the three NDVI datasets in Chinese drylands, thereby combating desertification and reducing dust storms.

In order to make full use of the absolute position information of fault signal, this paper designs a new multi-head attention (MHA) mechanism focusing on data positional information, proposes a novel MHA-based fault diagnosis method and extends it to the fault diagnosis scenario with missing information. Based on the absolute positional information and the trainable parameter matrix of the fault data, a novel attention weight matrix is generated, and the fault features are extracted by a fully connected network with the attention mechanism. By integrating the positional information into the weight matrix, the new MHA mechanism has the ability to extract more effective data features, compared with the traditional MHA method. Furthermore, the proposed method is also developed for the fault diagnosis scenarios with missing information. A special attention weight modified method is designed to reduce the impact of missing data on fault diagnosis results. In the experiment simulations, the data sampled from ZHS-2 multi-function motor flexible rotor test bed and the Tennessee- Eastman process data are utilized to test the performance of the algorithm. The results show that the proposed method can effectively extract fault features and reduce the impact of missing data.

Selenium plays a vital role in cancer prevention, antioxidation, and the growth of humans and other vertebrates. Excessive selenium can cause liver injury and metabolic disorders, which can lead to hepatic disease, but few studies have shown the effects of excessive selenium on liver development and its mechanism in zebrafish embryos. In this study, liver development and glucolipid metabolism were investigated in selenium-stressed zebrafish embryos. Under selenium treatment, transgenic fabp10a-eGFP zebrafish embryos showed reduced liver size, and wild-type zebrafish embryos exhibited steatosis and altered lipid metabolism-related indexes and glucose metabolism-related enzyme activities. In addition, selenium-stressed embryos exhibited damaged mitochondria and inhibited autophagy in the liver. An autophagy inducer (rapamycin) alleviated selenium-induced liver injury and restored the expression of some genes related to liver development and glucolipid metabolism. In summary, our research evaluated liver developmental toxicity and metabolic disorders under selenium stress, and confirmed that autophagy and oxidative stress might involve in the selenium-induced hepatic defects.

A tenon connection structure is widely used for the blade-disk connection in turbomachinery, and its ability to resist wear influences operation life. The finite element method (FEM) has been extensively applied in predicting fretting wear due to its advantage in solving problems like the non-linearity of boundary conditions. This work proposes a model that combines a modified Archard model with FEM to simulate fretting wear in multiple pairs of contact curved surfaces of the tenon connection structure. The model considers various factors, including the direction of fretting, time, load magnitude, and the application of aerodynamic load. The results indicate that the direction of fretting has a significant effect on the wear of the tenon connection structure. The wear depth of the tenon connection structure caused by axial fretting is nearly twice that of circumferential and radial fretting, and the corresponding wear depth values are 57.22, 30.85, and 24.36 µm in this study, respectively, and the rate of change in wear depth increases over time, while the contact pressure decreases initially and then increases with continuous wear. This study provides valuable insight into the impact of fretting under different working conditions on the wear of turbine tenon connection structures, which is of great significance for their wear-resistant design and life prediction.

Abstract Background Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown. Methods Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining. Results OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin–proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels. Conclusions These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC. Video Abstract

With the ever-increasing number of large-span shield tunneling projects and the extended operational time, their distinctive internal component issues are becoming more pronounced and exhibiting unique characteristics. In order to reveal the cracking mechanism of concrete on the top of the middle partition wall, based on a large-span shield tunnel section of Nanjing Metro, the crack mode, distribution characteristics, and cracking process of concrete inside tunnel structure were studied by combined field investigation and extended finite element analysis. The results showed that: (1) there were 96 cracks of concrete on the top of the middle partition wall in the interval. Based on the propagation path, number, and shape of cracks, they could be divided into type I, II, III, Y, and Z, with type-Y and type-Z being subtypes of type-I. (2) The crack started at the opposite side of horizontal differential displacement of the flue plate. The development curves of the length and end width of type-I and type-II cracks showed the significant characteristics of three stages. The relationship between crack end width and length was nonlinear, showing that 250 and 225 mm, respectively, were the critical crack lengths growing with the rapid growth of the end width of type-I and type-II cracks. (3) In type-II cracks, the propagation curves of two cracks under the same working condition were consistent, and the spacing of plate joints greatly influenced the length and slope of each stage of the curve. For type-III cracks, the first crack propagation process was basically consistent with type-I and type-II cracks, and the propagation of the other two cracks had obvious brittle characteristics.

Polymer gels have been effectively employed as a water management material for profile control and water shutoff treatments in low-middle temperature and low-middle salinity reservoirs. However, most polymer gel systems have limitations under high temperature and salinity reservoir conditions, such as short gelation time, poor strength, and long-term instability. Therefore, several researchers have developed enhanced polymer gels to satisfy the water control requirements in high temperature and salinity reservoirs. This work reviews the five main types of enhanced polymer gels that have been developed so far: nano silica-enhanced gel systems, cellulose-enhanced gel systems, graphite-enhanced gel systems, oily sludge-enhanced gel systems, and foam-enhanced polymer gel systems. Further, this article investigates the fundamental properties, strengthening and crosslinking mechanisms, reservoir application conditions, and field applications of several enhanced polymer systems. In this paper, it is found that the addition of strengthening materials can increase the bound water content in the gel network and significantly improve the temperature and salt resistance of polymer gel, so as to cope with the application of profile control and water plugging in high temperature and high salt reservoirs. Moreover, it also offers references and future research directions for enhanced polymer gel systems.

Lactate is an important bulk chemical with widespread applications and a major byproduct of other chemicals bioprocess in microbial fermentation. Lactate dehydrogenase A (LdhA) catalyzes the synthesis of lactate from pyruvate. Lysine acetylation is an evolutionarily conserved post-translational modification; however, the mechanisms underlying the regulation of LdhA function by lysine acetylation in Escherichia coli remain poorly understood. Herein, we demonstrate acetylation of E. coli LdhA occurs via enzymatic and non-enzymatic mechanisms. Further, we show carbon source type and concentration affect the lysine acetylation status of LdhA via a non-enzymatic mechanism. Lysine acetylation significantly inhibits the enzymatic activity and protein level of LdhA. The results of the present study demonstrate lysine acetylation of E. coli LdhA is irreversible. Understanding of the effects of lysine acetylation on LdhA function may provide a new perspective for regulating lactate production in microbial synthesis.

Drought plays a prominent role in affecting ecosystem stability and ecosystem productivity. Based on eddy covariance and climatic observations during 2012–2020, the Fisher discriminant analysis method was employed to accurately detect drought occurrences. Furthermore, the ecosystem water sensitivity and its resistance to drought were quantified to evaluate the ecosystem stability. The results showed that the alpine meadow suffered drought most frequently at the beginning of the growing seasons. However, drought during the peak growing seasons reduced the gross primary productivity (GPP) the most, by 30.5 ± 15.2%. In the middle of the peak growing seasons, the ecosystem water sensitivity was weak, and thus, the resistance to drought was strong, which resulted in high ecosystem stability. At the beginning and end of the peak growing seasons, the ecosystem stability was relatively weak. Ecosystem stability was positively related to the corresponding multiyear average soil water content (SWCave). However, drought occurring during high SWCave periods led to larger reductions in GPP, which indicated that the inhibitory effects of drought on ecosystems were more dependent on the occurrence time of droughts than on ecosystem stability.

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

Abstract Ecosystem trait is a standardized description of biological features of a community, and it bridges individual plants and ecosystem. Conventionally most ecosystem trait data are collected from field survey and the generated data is hard to meet the requirements as set in the concept of ecosystem trait. To a great extent, remotely piloted aircraft systems (RPAS) remote sensing, which is capable of retrieving ecosystem traits across multiple scales, can overcome constraints in field plot survey. In this study, we selected alpine grassland ecosystem on the Tibetan Plateau (TP), which is under‐studied due to scarcity of field monitoring data, as the research target. A new data framework was proposed by integrating field plot and RPAS remote sensing data to map spatial patterns of ecosystem traits for the alpine grasslands. Across four landscapes on the TP, ecosystem traits of vegetation coverage (CVC), species number (CSN), individual number (CIN), above ground biomass (AGB), organic carbon content (OC%) and total nitrogen content (TN%) were retrieved. We also calculated Shannon's Diversity Index and Shannon's Evenness Index for each plot. The results showed that RPAS‐based high spatial resolution RGB image is capable of predicting both physical and chemical ecosystem traits for alpine grasslands on the TP. Remote sensing on physical traits are overall more efficient than on chemical traits, with the highest R2 of 0.86 and 0.48 for physical trait and chemical one, respectively. The bands of Red and Green contributed more to the prediction model than band of Blue did, and the spectral mean value played a greater role than the spectral standard deviation. Based on the retrieved results, a set of spatial patterns on ecosystem traits can be revealed. This study represents an advance on ecosystem trait study and can significantly improve our understanding on ecosystem functions of the alpine ecosystem on the TP.

Water-land ecotone is a core area of wetlands which play an important role in ecological function. The information of vegetation type on the water-land ecotone is important for detecting the health of the wetland, and its protection. Seasonal flooding is a key factor in controlling the environment in water-land ecotone. Even preventing direct detection of the flooded vegetation with satellites, seasonal flooding has effects on the distribution of plants, which may provide potential information on vegetation classification with satellites. Therefore, the study induces flooding index in vegetation mapping in water-land ecotone with satellites. We applied Sentinel-1 and Sentinel-2 images to map vegetation in the Dongting Lake with random forest method. The Sentinel-1 SAR images were used to obtain the flooding index (i.e. inundation frequency), and Sentinel-2 images were applied to acquire the optical characteristic of vegetation. A comparative experiment based on whether the flooding index was added or not during vegetation mapping in the Dongting Lake was carried out to explore the role of flooding index in vegetation mapping. The results concluded that (1) seasonal flooding will hinder vegetation mapping using a single phase of optical information; (2) the classification accuracy of single phase scenario was significantly improved with the aid of flooding index especially in wet season; (3) the classification accuracy can be somewhat improved by adding flooding index for the multi-temporal scenario. The study implies that inundation frequency information can be used for vegetation mapping in water-land ecotone, especially for complex regions with insufficient cloud-free satellite images.

ABSTRACT The two-component system CpxRA can sense environmental stresses and regulate transcription of a wide range of genes for the purpose of adaptation. Despite extensive research on this system, the identification of the CpxR regulon is not systematic or comprehensive. Herein, genome-wide screening was performed using a position-specific scoring matrix, resulting in the discovery of more than 10,000 putative CpxR binding sites, which provides an extensive and selective set of targets based on sequence. More than half of the candidate genes ultimately selected (73/97) were experimentally confirmed to be CpxR-regulated genes through experimental analysis. These genes are involved in various physiological functions, indicating that the CpxRA system regulates complex cellular processes. The study also found for the first time that the CpxR-regulated genes ydeE, xylE, alx, and galP contribute to Escherichia coli resistance to acid stress, whereas prlF, alx, casA, yacH, ydeE, sbmA, and ampH contribute to E. coli resistance to cationic antimicrobial peptide stress. Among these CpxR-regulated genes, ydeE and alx responded to both stressors. In a similar way, a cationic antimicrobial peptide is capable of directly activating the periplasmic domain of CpxA kinase in vitro, which is consistent with the CpxA response to acid stress. These results greatly expand our understanding of the CpxRA-dependent stress response network in E. coli. IMPORTANCE CpxRA system is found in many pathogens and plays an essential role in sensing environmental signals and transducing information inside cells for adaptation. It usually regulates expression of specific genes in response to different environmental stresses and is important for bacterial pathogenesis. However, systematically identifying CpxRA-regulated genes and elucidating the regulative role of CpxRA in bacteria responding to environmental stress remains challenging. This study discovered more than 10,000 putative CpxR binding sites based on sequence. This bioinformatics approach, combined with experimental assays, allowed the identification of many previously unknown CpxR-regulated genes. Among the novel 73 CpxRA-regulated genes identified in this study, the role of nine of them in contributing to E. coli resistance to acid or cationic antimicrobial peptide stress was studied. The potential correlation between these two environmental stress responses provides insight into the CpxRA-dependent stress response network. This also improves our understanding of environment-bacterium interaction and Gram-negative pathogenesis.

Background: As a new style of cell death, necroptosis plays a crucial role in tumor immune microenvironment. LncRNAs have been identified to act as competitive RNAs to influence genes involved in necroptosis. Therefore, we aim to create a signature based on necroptosis-related lncRNAs to predict the prognosis and immune landscape of lung adenocarcinoma (LUAD) patients in this study.Methods: TCGA database was used to acquire RNA sequencing (RNA-Seq) data and clinical information for 59 lung normal samples and 535 lung adenocarcinoma samples. The Pearson correlation analysis, univariate cox regression analysis and least absolute shrinkage and selection operator (LASSO) cox regression were performed to construct the prognostic NRlncRNAs signature. Then we used Kaplan-Meier (K-M) analysis, time-dependent ROC curves, univariate and multivariate cox regression analysis, and nomogram to validate this signature. In addition, GO, KEGG, and GSVA were analyzed to investigate the potential molecular mechanism. Moreover, we analyzed the relationship between our identified signature and immune microenvironment, TMB, and some clinical characteristics. Finally, we detected the expression of the six necroptosis-related lncRNAs in cells and tissues.Results: We constructed a NRlncRNAs signature consisting of six lncRNAs (FRMD6-AS1, LINC01480, FAM83A-AS1, FRMD6-AS1, MED4-AS1, and LINC01415) in LUAD. LUAD patients with high risk scores had lower chance of survival with an AUC of 0.739, 0.709, and 0.733 for 1-year, 3-year, and 5-year respectively. The results based on GO, KEGG, and GSVA enrichment analysis demonstrated that NRlncRNAs signature-related genes were mainly correlated with immune pathways, metabolic-and cell growth-related pathways, cell cycle, and apoptosis. Moreover, the risk score was correlated with the immune status of LUAD patients. Patients with higher risk scores had lower ESTIMATE scores and higher TIDE scores. The risk score was positively correlated with TMB. LINC01415, FRMD6-AS1 and FAM83A-AS1 were significantly overexpressed in lung adenocarcinoma, while the expression levels of MED4-AS1 and LINC01480 were lower in lung adenocarcinoma.Conclusion: Overall, an innovative prognostic signature based on NRlncRNAs was developed for LUAD through comprehensive bioinformatics analysis, which can act as a predictor of immunotherapy and may provide guidance for clinicians.

BackgroundType 2 diabetes (T2DM) is a major risk factor for myocardial infarction. Thrombus aspiration was considered a good way to deal with coronary thrombus in the treatment of acute myocardial infarction. However, recent studies have found that routine thrombus aspiration is not beneficial. This study is designed to investigate whether intracoronary artery retrograde thrombolysis (ICART) is more effective than thrombus aspiration or percutaneous transluminal coronary angioplasty (PTCA) in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).Methods/DesignIntraCoronary Artery Retrograde Thrombolysis (ICART) vs. thrombus aspiration or PTCA in STEMI trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 286 patients with STEMI undergoing PPCI are randomly assigned to two groups: ICART and thrombus aspiration or PTCA. The primary endpoint is the incidence of >70% ST-segment elevation resolution. Secondary outcomes include distal embolization, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, and in-hospital bleeding.DiscussionThe ICART trial is the first randomized clinical trial (RCT) to date to verify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in patients with STEMI undergoing PPCI.Clinical Trial Registration[https://www.chictr.org.cn/], identifier [ChiCTR1900023849].

As an evolutionarily conserved posttranslational modification, protein lysine acetylation plays important roles in many physiological and metabolic processes. However, there are few reports about the applications of lysine acetylation in metabolic regulations. Lactate is a main byproduct in microbial fermentation, and itself also an important bulk chemical with considerable commercial values in many fields. Lactate dehydrogenase (LdhA) is the key enzyme catalyzing lactate synthesis from pyruvate. Here, we reported that Escherichia coli LdhA can be acetylated and the acetylated lysine sites were identified by mass spectrometry. The effects and regulatory mechanisms of acetylated sites on LdhA activity were characterized. Finally, lysine acetylation was successfully used to regulate the lactate synthesis. LdhA (K9R) mutant overexpressed strain improved the lactate titer and glucose conversion efficiency by 1.74 folds than that of wild-type LdhA overexpressed strain. LdhA (K154Q-K248Q) mutant can inhibit lactate accumulation and improve 3HP production. Our study established a paradigm for lysine acetylation in lactate synthesis regulation and suggested that lysine acetylation may be a promising strategy to improve the target production and conversion efficiency in microbial synthesis. The application of lysine acetylation in regulating lactate synthesis also provides a reference for the treatment of lactate-related diseases.

BackgroundOvarian-tumor (OTU) domain-containing protein 6B (OTUD6B), one of newly identified OTU deubiquitylating enzyme families, is proved to be associated with tumor progression. However, whether it plays a key role in pan-cancer still remains unknown.MethodsThe profiles of OTUD6B expression in multiple cancers were analyzed using The Cancer Genome Atlas (TCGA) database. Information of protein expression was performed based on the HPA, GeneCards, and String databases. K-M plotter and survival data analysis were used to analyze the prognostic value of OTUD6B expression, including overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). R package “clusterProfiler” was used for enrichment analysis of OTUD6B. Furthermore, we analyzed the correlation between the expression of OTUD6B, immune infiltration, and immune-related genes. Additionally, we preliminarily validated its tumorigenic effect in lung cancer cell lines.FindingsOTUD6B expression was upregulated in most cancers, such as COAD, CHOL, and LUAD, and predicted poor prognosis in most cancers in TCGA. Results showed that OTUD6B expression was positively correlated with memory CD4+ T cells, Th1 CD4+ T cells, and CD8+ T cells. In terms of the immune-related genes, OTUD6B was found to be associated with most types of genes, such as immunostimulatory genes KDR, TGFBR1, and IL-10. Moreover, for most types of tumors, the immune score was found to be negatively correlated with OTUD6B expression. In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells.ConclusionsThe study indicated that OTUD6B is an oncogene and may serve as a new potential biomarker in various tumors. OTUD6B may play a part in TIME, which could be applied as a new target for cancer therapy.

Increasing evidence showed that the dysregulation of DNA methylation regulators is a decisive feature of almost all cancer types and affects tumor progressions. However, few studies focused on the underlying influences of DNA methylation regulators-related genes (DMRegs) in immune cell-infiltration characteristics, tumor microenvironment (TME) and immunotherapy in HCC patients. In our study, the alterations of DNA methylation regulators modification patterns (DMRPs) were clustered from hepatocellular carcinoma (HCC) samples based on the expression of DNA methylation regulators as well as genetic and transcriptional features. In addition, based on molecular identification of three distinct molecular subtypes, we found that different DMRPs alterations were related to different clinicopathological characteristics, prognosis, and immune cells infiltration features. Moreover, we constructed and validated a DNA methylation regulators-related genes score (DMRegs_score) to predict the survival of HCC patients. A high DMRegs _score, which was characterized by more TP53 wild mutation, high expression of PD-1, CTLA-4, and remarkable immunity activation, was indicative of poor prognosis. Furthermore, we validated the expression of eight genes which were used for the prognostic signature in this risk score by RT-qPCR using tissues from our center. More importantly, DMRegs_score was highly correlated with targeted drug sensitivity. Additionally, we developed a highly accurate scoring system that could be used to improve the clinical applicability of DMRegs _score. In conclusion, these findings may contribute to a better understanding of DNA methylation regulators and provide new strategies for evaluating prognosis and developing more effective combination therapy for HCC patients.

Selenium is an essential micronutrient derived from daily diet to maintain the normal growth and development of vertebrates. Excessive selenium intake will induce cardiovascular toxicity, reproductive toxicity and neurotoxicity. However, there have been few studies of the toxic effects of selenium on neural development and locomotor behavior. In this study, newly fertilized zebrafish embryos were treated with selenium. As a result, selenium treatment at the concentration of 0.5 µM decreased the moving speed and distance and blunted the touch response of zebrafish embryos. TUNEL assay and immunofluorescence analysis revealed that selenium induced nervous system impairment including promoted cell apoptosis, proliferation and neuroinflammation, and decreased neurons in zebrafish embryos. RNA-seq and RT-PCR results indicated that selenium treatment significantly decreased the expression of the dopaminergic neuron, motor neuron, GABAergic neuron and neurotransmitter transport marker genes in zebrafish embryos. The expression of PPAR signaling pathway marker genes was significantly down-regulated in selenium-treated embryos. Two PPAR agonists (rosiglitazone and bezafibrate) and an anti-cancer drug (cisplatin) were tested for their effects to alleviate selenium-induced locomotor defects. Rosiglitazone and bezafibrate could restore the expression of some neural marker genes but could not fully rescue the selenium-induced locomotor behavior defects. The supplementation of cisplatin could restore the dysfunctional locomotor behavior and the abnormal expression of the PPAR and neural marker genes to almost the normal levels. In conclusion, the results of this study reveal that selenium-induced neural development and locomotor behavior defects are caused by multiple complex factors including PPAR signaling, and all the factors might be recovered by cisplatin through unknown mechanisms.

As an indispensable material for animals, plants and human beings, obtaining accurate water body information rapidly is of great significance to maintain the balance of ecosystems and ensure normal production and the life of human beings. Due to its independence of the time of day and the weather conditions, synthetic aperture radar (SAR) data have been increasingly applied in the extraction of water bodies. However, there is a great deal of speckle noise in SAR images, which seriously affect the extraction accuracy of water. At present, most of the processing methods are filtering methods, which will cause the loss of detailed information. Based on the characteristic of side-looking SAR, this paper proposed a self-adaptive thresholding approach for automatic water extraction based on an OTSU algorithm and distance block. In this method, the whole images were firstly divided into uniform image blocks through a distance layer which was produced by the distance to the orbit. Then, a self-adaptive processing was conducted for merging blocks. The OTSU algorithm was used to obtain a threshold for classification and the Jeffries–Matusita (JM) distance was calculated with the classification result. The merge processing continued until the separability of image blocks reached the maximum. Subsequently, we started from the next block to repeat the merger, and so on until all blocks were processed. Ten study areas around the world and the local Dongting Lake area were applied to test the feasibility of the proposed method. In comparison with five other global threshold segmentation algorithms such as the traditional OTSU, MOMENTS, MEAN, ISODATA and MINERROR, the proposed method obtains the highest overall accuracy (OA) and kappa coefficient (KC), while this approach also demonstrates greater robustness in the analysis of time series. The findings of this study offer an effective method to improve water detection accuracy as well as reducing the influence of speckle noise and retaining details in the image.

The Tibetan Plateau (TP) is one of the most important areas for the study of the carbon budgets of terrestrial ecosystems. However, the estimation of the net ecosystem productivity (NEP) remains uncertain in this region due to its complex topographic properties and climatic conditions. Using CO2-eddy-covariance-flux data from 1982 to 2018 at 18 sites distributed around the TP grassland, we analyzed the spatial–temporal patterns of the grassland NEP and its driving factors from 1982 to 2018 using a random forest (RF) model. Our results showed that the RF model captured the size of the carbon sink (R2 = 0.65, p < 0.05) between the observed and simulated values for the validation samples. During the observation period, the grassland acted as a carbon sink of 26.2 Tg C yr−1 and increased significantly, by 0.4 g C m−2 yr−1. On a regional scale, the annual NEP gradually increased from the northwest to the southeast, and a similar pattern was also observed in the long-term trends. Furthermore, the moisture conditions, such as the specific humidity and precipitation, were proven to be the main driving factors of the carbon flux in the southeastern areas, while the temperature predominantly controlled the carbon flux in the northwest. Our results emphasize the net carbon sink of the TP and provide a reliable way to upscale NEP from sites.

Abstract Background A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins. Methods A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D