Search

Abstract Bone marrow mesenchymal stem cells (BMMSCs) have garnered attention as promising therapeutic modalities for spinal cord injury (SCI) due to their neuroregenerative, anti-apoptotic, and functional recovery-enhancing properties. The central role of microRNAs (miRNAs) in mediating the beneficial outcomes resulting from BMMSCs in SCI has been highlighted in recent studies, suggesting that targeted modulation of specific miRNAs holds potential for augmenting SCI recovery. Our previous investigation implicated miR-202-3p in the reparative processes of injured spinal cords, although the precise mechanistic underpinnings remain elusive. In vivo, BMMSCs were administered to SCI rats, while in vitro, miR-202-3p was transfected into PC-12 cells. Motor capabilities recovery was assessed via Basso-Beattie-Bresnahan (BBB) scores and footprinting tests; the evaluation of neuronal and spinal cord tissue repair was conducted using Nissl staining, TUNEL staining, hematoxylin and eosin (HE) staining, and immunofluorescence; and the impacts of miR-202-3p on cellular autophagy, neuronal apoptosis, and relevant pathways were evaluated using Western blotting, quantitative polymerase chain reaction (qPCR), and transmission electron microscopy (TEM). Functionally, BMMSCs utilized miR-202-3p to improve motor recovery in SCI rats. Histopathologically, they contributed to the repair of damaged spinal cords and the regeneration of nerve axons. At the molecular level, BMMSCs stimulated autophagy and suppressed neuronal apoptosis by regulating the AMPK, MAPK, and PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that BMMSCs coordinate miR-202-3p to inhibit mTOR activation via the AMPK, MAPK, and PI3K/AKT pathways, thereby promoting TFEB dephosphorylation, modulating autophagy and neuronal apoptosis, and ultimately fostering functional recovery post-SCI.

A reusable reentry vehicle requires a thermal protection structure with high strength and heat resistance for repeated traveling between the Earth and space. In this study, various transition modes of TiC/Ti6Al4V graded materials were designed and fabricated by direct energy deposition, and then ablation tests were conducted to simulate the service environment. The influence of microstructure morphology on the heat resistance of the graded materials was revealed by analyzing the changes in the internal microstructure, element distribution, and microcrack. Compared with Ti6Al4V titanium alloy, TiC/Ti6Al4V graded materials show almost no mass loss or ablation pits, indicating a significant improvement in heat resistance. The Ti6Al4V titanium alloy exhibited macroscopic cracks up to 700 μm in length on the surface after the ablation test; as a contrast, the surface area of the TiC/Ti6Al4V graded materials exhibited fine microcracks, and there were no significant changes in the internal structure. The improvement in the heat resistance of TiC/Ti6Al4V graded materials is attributed to the combined effects of the interface heat resistance between the TiC and Ti6Al4V and the change of heat conduction path within the matrix.

Abstract Background Quantitative mapping of the brain’s metabolism is a critical tool in studying and diagnosing many conditions, from obesity to neurodegenerative diseases. In particular, noninvasive approaches are urgently required. Recently, there have been promising drug development approaches for the treatment of disorders related to glucose metabolism in the brain and, therefore, against obesity-associated diseases. One of the most important drug targets to emerge has been the Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R). GLP and GLP-1R play an important role in regulating blood sugar and maintaining energy homeostasis. However, the macroscopic effects on brain metabolism and function due to the presence of GLP-1R are unclear. Methods To explore the physiological role of GLP-1R in mouse brain glucose metabolism, and its relationship to brain function, we used three methods. We used deuterium magnetic resonance spectroscopy (DMRS) to provide quantitative information about metabolic flux, fluorodeoxyglucose positron emission tomography (FDG-PET) to measure brain glucose metabolism, and resting state-functional MRI (rs-fMRI) to measure brain functional connectivity. We used these methods in both mice with complete GLP-1R knockout (GLP-1R KO) and wild-type C57BL/6N (WT) mice. Results The metabolic rate of GLP-1R KO mice was significantly slower than that of WT mice (p = 0.0345, WT mice 0.02335 ± 0.057 mM/min, GLP-1R KO mice 0.01998 ± 0.07 mM/min). Quantification of the mean [18F]FDG signal in the whole brain also showed significantly reduced glucose uptake in GLP-1R KO mice versus control mice (p = 0.0314). Observing rs-fMRI, the functional brain connectivity in GLP-1R KO mice was significantly lower than that in the WT group (p = 0.0032 for gFCD, p = 0.0002 for whole-brain correlation, p

Objective Bone transport has become the gold standard for treating large segmental tibial bone defects. The technique for application the Ilizarov circular fixator (ICF) has a long learning curve and is associated with many complications. There are few clinical studies on bone transport via the Taylor spatial frame (TSF). The main purpose of this study was to compare the radiological and clinical and outcomes of bone transport by using the TSF and the ICF. Methods There were 62 patients included in this retrospective study from June 2011 to June 2021 and distributed to two groups according to the fixation method: a TSF group consisting of 30 patients and an ICF group consisting of 32 patients. Demographic information, surgical duration, external fixation times, external fixation index, final radiographic results, complications, and clinical outcomes were recorded and examined. The clinical outcomes were assessed using the ASAMI criteria during the most recent clinical visit. Then, statistical analysis such as independent‐samples t tests or chi‐Square test was performed. Results The mean surgical duration in the TSF group was 93.8 ± 7.3 min, which was shorter than that in the ICF group (109.8 ± 1.4 min) (p 0.05). The external fixation index was 1.4 ± 0.2 m/cm and 1.5 ± 0.1 m/cm in the two groups. Moreover, there was no significant difference between the two groups. At the last follow‐up visit, the medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) in the TSF group were 88.1 ± 12.1° and 80.9 ± 1.3°, respectively. The MPTA and PPTA in the ICF group were 84.4 ± 2.4° and 76.2 ± 1.9°, respectively. There were statistically significant differences between the two groups (all p 0.05). Conclusion No statistically significant difference was found in clinical outcomes between the use of Taylor spatial frame and Ilizarov circular fixator for treating large segmental tibial bone defects. However, TSF is a shorter and simpler procedure that causes fewer complications and improves limb alignment.

Visual Attention Prediction (VAP) is widely applied in GIS research, such as navigation task identification and driver assistance systems. Previous studies commonly took color information to detect the visual saliency of natural scene images. However, these studies rarely considered adaptively feature integration to different geospatial scenes in specific tasks. To better predict visual attention while driving tasks, in this paper, we firstly propose an Adaptive Feature Integration Fully Convolutional Network (AdaFI-FCN) using Scene-Adaptive Weights (SAW) to integrate RGB-D, motion and semantic features. The quantitative comparison results on the DR(eye)VE dataset show that the proposed framework achieved the best accuracy and robustness performance compared with state-of-the-art models (AUC-Judd = 0.971, CC = 0.767, KL = 1.046, SIM = 0.579). In addition, the experimental results of the ablation study demonstrated the positive effect of the SAW method on the prediction robustness in response to scene changes. The proposed model has the potential to benefit adaptive VAP research in universal geospatial scenes, such as AR-aided navigation, indoor navigation, and street-view image reading.

Human visual attention is the basis of target recognition, change detection and classification in remote sensing images. However, the human visual attention of remote sensing images during target detection remains uninvestigated. In this study, we simultaneously collected eye tracking and electroencephalography (EEG) data of 40 experts during target detection in 1000 remote sensing images. We quantified their attention in different phases of target detection (i.e., target search, selection, and identification) from their eye movements and brain activities. The eye-tracking results indicated that hue and lightness were crucial visual features that guided visual search for remote sensing images. The size of the target also affected the allocation of human attention resources. Particularly, participants tended to miss the targets that were smaller than 3.9 % of the whole image area. The fixation event-related potentials (FRPs) in temporal and parietal brain regions further distinguished the attention of targets and distractors, which could be attributed to the process of memory and processing. Our findings offer new visual and neural evidence for human attention in target detection of remote sensing images, which not only contribute to the performance of attention-based algorithms in remote sensing interpretation, but also provide an empirical basis for guiding human–machine intelligent fusion.

Abstract Background It’s difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs. Methods A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit. Results There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P

This technology is highly suitable for detecting and tracking multi-skeletal targets in the field of aerial refueling. The paper presents a target feature responder based on K-means clustering, used for categorizing samples and training models. It employs a decision function to optimize the localization region across various classifier detection and tracking algorithms for targets. Additionally, a state judgment module scores the classifiers based on target state and depth information, which allows for adaptive selection of the classifier. To address the issue of missing target information, the method incorporates a stereo-vision-based mechanism to complete the localization region. This approach effectively handles challenges related to target appearance deformation, significant scale variations, motion blur, and occlusions.

N-acetyltransferase 10 (NAT10) is acknowledged as a tumor promoter in various cancers due to its role as a regulator of acetylation modification. Tumor-associated macrophages (TAMs) play a pivotal role in the tumor microenvironment (TME). However, the intercellular communication between esophageal squamous cell carcinoma (ESCC) cells and TAMs involving NAT10 remains poorly understood. This study aimed to elucidate the regulatory mechanism of NAT10 in modulating macrophage lipid metabolism and polarization. Experimental evidence was derived from in vitro and in vivo analyses. We explored the association between upregulated NAT10 in ESCC tissues, macrophage polarization, and the therapeutic efficacy of PD-1. Furthermore, we investigated the impact of methyltransferase 3 (METTL3)-induced m6A modification on the increased expression of NAT10 in ESCC cells. Additionally, we examined the role of exosomal NAT10 in stabilizing the expression of fatty acid synthase (FASN) and promoting macrophage M2 polarization through mediating the ac4C modification of FASN. Results indicated that NAT10, packaged by exosomes derived from ESCC cells, promotes macrophage M2 polarization by facilitating lipid metabolism. In vivo animal studies demonstrated that targeting NAT10 could enhance the therapeutic effect of PD-1 on ESCC by mediating macrophage reprogramming. Our findings offer novel insights into improving ESCC treatment through NAT10 targeting.

Introduction: Congenital bronchial atresia (CBA), as a rare developmental abnormality of the lung, is usually asymptomatic and is accidently discovered in most cases. Currently, no standardized guidelines for the treatment or management of CBA have been established. Case presentation: A 22-year-old male soldier was referred to Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University due to chest tightness and shortness of breath after repeated strenuous activities. Contrast-enhanced computed tomography (CT) revealed an 18mm × 11mm solitary, well-circumscribed, and solid nodule with no enhancement in the right upper lobe (RUL), and emphysematous changes distributed throughout the RUL. A flexible bronchoscopic examination showed extrinsic compression stenosis in the bronchial opening of the right middle lobe (RML). After three-dimensional (3D) reconstruction CT and a multidisciplinary consultation, a diagnosis of CBA in the anterior segment (B3) of RUL was established. Subsequently, thoracoscopic right upper lobectomy was performed and resulted in an improved respiratory capacity 6 months after surgery. To date, the patient has good quality of life without any complication. Conclusion: This study underscores the role of bronchoscopy, 3D reconstruction CT, and a multidisciplinary consultation in the diagnosis of CBA, and highlights that a thoracoscopic intervention should be considered in such case.

Laser melting deposition (LMD) is an additive manufacturing technology that involves complex thermodynamic and kinetic characteristics in the molten pool. A perspective on the thermal-fluid dynamic behavior in the molten pool is essential for investigating the microstructure morphology and solidification characterization. In this study, a three-dimensional transient thermal-fluid coupling model is proposed for describing thermal-fluid dynamic behavior within the molten pool during laser melting deposition of TiC/Ti6Al4V functionally graded materials. The simulated temperature distribution and deposition layer morphology agree well with the experimental results. The simulation results indicate that the heat accumulation phenomenon generated during the LMD process can exacerbate the penetration effect of the molten pool. The solidified deposition layer will be remelted to form a large cross-layer molten pool, and the molten metal in the remelted zone will move from the lower layer to the upper layer driven by the Marangoni convection. Furthermore, the unmelted TiC particles and the in-situ generated TiC particles can decrease the free energy of the molten pool, induce heterogeneous nucleation, and promote the growth of equiaxed crystals.

Abstract As deep gas-condensate reservoirs are explored, the problem of paraffin deposition is becoming more prominent. Therefore, this paper collects condensate samples from representative paraffin deposition gas-condensate wells and analyzes basic physical properties. The cold plate deposition device is employed to study paraffin deposition behavior under well conditions and to divide the critical regions for paraffin deposition in gas-condensate wells. The experimental apparatus, such as the crude oil dynamic paraffin deposition rate tester, is utilized to investigate the preventive effect of paraffin dispersants and paraffin crystal modifier. The results show that there is significant phase change behavior in gas-condensate wells and gas phase is dominant form, but there is also phase evolution. It can be identified from the experiments that paraffin deposition is mainly located in the 1000 ~ 1500 m region, and a paraffin deposition identification chart has been established. The maximum deposition rate could reach 15.50 mm/year, which matched the temperature and pressure conditions of 45 ℃ and 70 MPa. The preventive effect of paraffin crystal modifiers greatly exceeds that of paraffin dispersants, with paraffin prevention rates of 85–95% at the optimal concentrations of 0.25–0.50 wt.%. The dissolving paraffin rate can reach 0.0169 g/min. It decreases the paraffin appearance temperature approximately 40% and significantly changes the paraffin crystal morphology. Increased deposition surface area of the cold plate structural design describes the paraffin deposition. This diagram facilitates the reliable identification of paraffin deposition areas and the deposition rates in the wellbore during production. The optimum amounts of BZ and PI paraffin inhibitors are quantified. This study provides a comprehensive understanding of the paraffin deposition behavior, and scientific basis and guidance for the selection of paraffin inhibitors in gas-condensate wells.

Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

Summary: This study was designed to explore the roles of CREB3L4 in the pathogenesis and drug resistance of hepatocellular carcinoma (HCC). The proliferation of HCC lines was determined in the presence of CREB3L4 over-expression and silencing. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay were performed to screen the potential target of CREB3L4 on mTORC1. Xenografted tumor model was established to define the regulatory effects of CREB3L4 in the tumorigenesis. Then we evaluated the roles of CREB3L4 in chemosensitivity to sorafenib treatment. CREB3L4 significantly induced the HCC cell proliferation by modulating the activation of mTROC1-S6K1 signaling pathway via binding with RHEB promoter. Moreover, CREB3L4 dramatically inhibited the chemosensitivity to sorafenib treatment via up-regulating RHEB-mTORC1 signaling. CREB3L4 promoted HCC progression and decreased its chemosensitivity to sorafenib through up-regulating RHEB-mTORC1 signaling pathway, indicating a potential treatment strategy for HCC through targeting CREB3L4.

Abstract The heterogeneity of neuroblastoma directly affects the prognosis of patients. Individualization of patient treatment to improve prognosis is a clinical challenge at this stage and the aim of this study is to characterize different patient populations. To achieve this, immune-related cell cycle genes, identified in the GSE45547 dataset using WGCNA, were used to classify cases from multiple datasets (GSE45547, GSE49710, GSE73517, GES120559, E-MTAB-8248, and TARGET) into subgroups by consensus clustering. ESTIMATES, CIBERSORT and ssGSEA were used to assess the immune status of the patients. And a 7-gene risk model was constructed based on differentially expressed genes between subtypes using randomForestSRC and LASSO. Enrichment analysis was used to demonstrate the biological characteristics between different groups. Key genes were screened using randomForest to construct neural network and validated. Finally, drug sensitivity was assessed in the GSCA and CellMiner databases. We classified the 1811 patients into two subtypes based on immune-related cell cycle genes. The two subtypes (Cluster1 and Cluster2) exhibited distinct clinical features, immune levels, chromosomal instability and prognosis. The same significant differences were demonstrated between the high-risk and low-risk groups. Through our analysis, we identified neuroblastoma subtypes with unique characteristics and established risk models which will improve our understanding of neuroblastoma heterogeneity.

Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.

Identifying the influence of heavy precipitation and ecological water replenishment (EWR) on groundwater resources is essential for groundwater resources management and risk prevention. This study innovatively developed a groundwater resource analysis and prediction model integrated with the water level fluctuation method, correlation analysis, and machine learning method under the influence of heavy precipitation and EWR. Water level fluctuation method results showed that compared with January 1, 2021, the groundwater resources of the study area increased 4.46 × 108 m3 on August 28. Compared with small flow of EWR, heavy precipitation was the main contributor to the rise in the groundwater level. Correlation analysis found that elevation, specific yield, and permeability coefficient show positive correlations with groundwater resource recharge. Machine learning results showed that among the water level prediction models of 35 monitoring wells, extreme gradient boosting (XGB) and random forest (RF) performed best in 30 wells and five wells, respectively. The increase in groundwater storage predicted deviated from the actual value by only 0.6 × 107 m3 (prediction bias of 1.3%), indicating that the model prediction performance was good under the heavy precipitation condition. This study can help to better understand the change trend of groundwater resources under the conditions of heavy precipitation and EWR. HIGHLIGHTS Through hydrology, statistics, and machine learning, groundwater changes under the dual effects of heavy precipitation and ecological water replenishment are studied.; A machine learning model is developed to predict the groundwater level and storage under heavy precipitation scenarios.; XGB and RF models well predicted the groundwater change the next day, and the prediction deviation was only 1.3%.;

Abstract Influentials play a key role in enhancing information diffusion on social media. However, how personal influence varies across multiple domains is rarely addressed. This study introduces a concept called Domain-Relevance of Influence to describe the relation between influence and domains, and establishes a methodological framework with a sample of 8,520,933 Weibo users to explore the cross-domain characteristics of influence. The results show that generalists with cross-domain attributes possess significantly higher influence than specialists in most domains, whereas in a single domain such as sports or technology, specialists and generalists can possess comparable influence. We further show that influence is positively associated with cross-domain capability in overall domains, but not necessarily in each single domain. This study contributes to better understanding of the influence variation across domains for influence enhancement, and provides a big data-based methodological basis for cross-domain communication research.

Atmospheric volatile organic compounds (VOCs), such as olefins and aromatics, released from synthetic chemical pesticide sprays can increase regional air pollution, public health risks, and food security risks. However, significant uncertainties remain regarding the measurement methods and chemical profiles of VOC emissions. Using an agricultural city, Changchun City in Northeast China, as a case study, we quantified real-time concentration and composition data based on online monitoring instruments for the year 2023. This study optimized data collection methods for emission factors and activity levels and developed a high-precision emission inventory of VOCs in pesticides at the city scale. The emission factors for VOCs from the seven categories of pesticides were estimated as follows: 78 g/kg (nicosulfuron and atrazine, oil-dispersible [OD] and suspension emulsion [SE], respectively), 4 g/kg (chlorpyrifos and indoxair conditioningarb, suspension concentrate [SC]), 5 g/kg (fluopicolide and propamocarb hydrochloride, SC), 217 g/kg (MCPA-dimethylammonium, aqueous solution [AS]), 34 g/kg (glyphosate, AS), 575 g/kg (beta-cypermethrin and malathion, emulsifiable concentrate [EC]), and 122 g/kg (copper abietate, emulsion in water [EW]), depending on the pesticide formulation components and formulation types. The orchard insecticide exhibited the highest emission factors among all pesticides owing to its emulsifiable concentrate formulation and 80% content of inactive ingredients (both factors contribute to the high content of organic solvents in the pesticide). The major components of VOC emissions from pesticide spraying were halocarbons (27–44%), oxygenated VOCs (OVOCs) (25–38%), and aromatic hydrocarbons (15–28%). The total VOC emissions from pesticide spraying in the Changchun region accounted for 10.6 t, with Yushu City contributing 28% of the VOC emissions and Gongzhuling City and Dehui City contributing 18.7% and 16.0%, respectively. Herbicides were the main contributors to VOC emissions because of their high emission factors and extensive use in fields (used for spraying maize and rice, the main crops in Changchun City). May and June exhibited the highest VOC emissions from pesticide application, with May accounting for 57.0% of annual pesticide emissions, predominantly from herbicides (95.1%), followed by insecticides (4.9%). June accounted for 30.1% of the annual pesticide emissions, with herbicides being the largest contributor of VOC emissions. An emission inventory of VOC with a monthly scale and spatial grid resolutions of 0.083° and 0.5° in 2023 was developed. These emission factors and inventories of pesticide applications provide valuable information for air quality modeling. This study also provides an important scientific basis for enhancing regional air quality and mitigating the environmental impact of pesticide use in major grain-producing areas.

Carbon dots-based phosphorescent composites have excellent room-temperature phosphorescent properties. However, the development of carbon dots-based phosphorescent materials that are excited by visible light and have adjustable colors remains a challenge. Here, we report on phosphorescent composites based on multicolored fluorescent carbon dots (CDs) and polyacrylamide (PAM) with four phosphorescent colors (blue, green, yellow and red). The phosphorescence of CDs@PAM composites is mainly derived from the C=O bonds of CDs. Electron transition of n-π* in the C=O bonds facilitates the intersystem crossover that are necessary to generate phosphorescence. In addition, the hydrogen bond actions between the amide groups of PAM polymer and the functional groups on CDs surface also promote the intersystem crossover and inhibit the non-radiative relaxation of triple states (T1) in CDs@PAM. Meanwhile, the PAM matrix provides a rigid protective environment (hydrogen bond mesh structure) that inhibits vibrations, rotations and collisions of the CDs' luminescent clusters (C=O), avoiding the rapid decay of phosphorescence. Four kinds of CDs based phosphorescence materials can produce brilliant phosphorescence under the excitation of visible light (flashlight). Finally, their colorful phosphorescent colors were used to achieve a naked-eye observable anti-counterfeit pattern, demonstrating the potential application of these materials.

The crosstalk between tumor cells and macrophages under hypoxic conditions has been acknowledged as a pivotal determinant in the progression of colorectal cancer (CRC). Previous research has underscored the significance of exosomes derived from hypoxic tumor cells in facilitating tumor progression through inducing the polarization of macrophages towards the M2-like phenotype. The precise influence of hypoxic macrophage-derived exosomes (HMDEs) on the progression of CRC has not yet been fully elucidated. The objective of this study was to investigate the role of HMDEs in the progression of CRC. We discovered that there was an elevated release of exosomes derived from macrophages in hypoxic conditions. Additionally, the hypoxia-induced macrophage-derived exosomes played a crucial role in promoting the progression of CRC. We have also demonstrated that HMDEs have the ability to induce cell cycle transition and inhibit cell apoptosis, thereby promoting the growth of CRC cells. Furthermore, the underlying molecular mechanisms of these effects have been identified. The overexpression of Hif-1α results in its direct interaction with distinct regions (-521− -516 bp and -401− -391 bp) of the Hsp90 promoter during hypoxic circumstances. This binding event led to the overexpression of Hsp90 and the subsequent elevation of Hsp90 protein levels within HMDEs. Importantly, the crucial interaction between Hsp90 and Lats1 resulted in the deactivation of Lats1 and the inhibition of Yap phosphorylation. Ultimately, this series of events lead to the deactivation of the Hippo signaling pathway. Our in vivo and in vitro studies presented compelling evidence for the crucial role of hypoxic macrophage-derived exosomal Hsp90 in promoting CRC progression through the inhibition of the Hippo signaling pathway. These findings represented a significant advancement in our comprehension of the complex interplay between macrophages and CRC cells under hypoxic conditions.

Combustion of herb residues (HRs) for heat recovery is a good way for their utilization, but there exists such a problem as high concentration NOx emission in flue gas. The alcohol extracted herb residue (AEHR), one special type of HRs, was chosen as the object and was subjected to immediate combustion in a fluidized bed reactor to investigate the characteristics of its resulting NOx emission. The results showed that, most of the NOx in the flue gas was produced from the char nitrogen (CN); as the fuel water content increased, the NOx emission concentration exhibited a trend of first decreasing and then increasing; and a properly low combustion temperature inhibited the NOx emission upon the premise of ensuring full combustion. Air staging combustion was adopted to effectively control NOx: the NOx emission concentration in the flue gas was reduced to 296 mg·m−3 and the NOx emission reduction rate reached 46.51 % compared to conventional combustion. Co-combustion by blending wasted activated coke (WAC) into the AEHR helped both stabilize the combustion state and reduce further the NOx emission. When the blending ratio of WAC fell within a proper range of 20–30 %, the NOx emission concentration in the flue gas was as low as 231.4 mg·m−3. In addition to the dilution effect of the combustion flue gas of the blended WAC, the local reducing atmosphere caused by its incomplete combustion as well as its strong absorbability and catalytical effect was accountable for the further decrease of the NOx emission concentration.

Wasted tofu rich in protein was subject to hydrothermal pretreatment (HTPT) under different conditions (at 120, 140, 160 and 180 ℃; for 0, 30, 60 and 90 min) followed by biochemical methane potential (BMP) tests, and 140 ℃ and 0 min were found to be respectively the best temperature and duration for HTPT of tofu in terms of its biogas production. Under the under the optimal conditions (140 ℃, 0 min) the accumulative methane yield reached up to 510.9 mL·(gVS)-1, which was 26.98 % higher than that without HTPT (402.3 mL·(gVS)-1). The start-up process of continuous anerobic digestion (AD) of the tofu before and after hydrothermal treated (HT) at the optimal HTPT conditions (140 ℃, 0 min) was examined, to investigate and compare how their consequent AD responded to HTPT. It was found that, for start-up of continuous AD, the HT tofu delivered more balanced nutrients and thus led to more stable AD and quicker biogas production. Unavoidably, HTPT generated products refractory to biodegradation, to slightly decrease the total biogas production. During AD of HT tofu some weak ammonia-tolerant microbes, such as methylotrophic methanogens, survived and played indispensable roles. Analyses of living microbial community structure indicated that, some hydrolytic acidification bacteria intolerant to ammonia nitrogen (such as Proteobacteria) were always active and appeared at high proportion. The viable methylotrophic methanogens, e. g. RumEn M2, took obvious responsibilities in start-up of the AD for HT tofu.

This paper presents a novel motor topology, called the End-Winding Flux Machine (EWM), which explores the potential function of end-windings in rotating electric machines. By introducing an axial-radial flux stator into the end-windings, a hybrid flux machine known as the End-Winding Hybrid Flux Machine (EHFM) is created, establishing an additional radial-axial flux circuit alongside the conventional radial-flux machine. The machine characteristics of the EHFM are validated through analytical calculations and transient 3-D finite-element method (FEM). Experimental investigations are conducted on a prototype EHFM, and the tested data is compared with FEM results. The EHFM exhibits enhanced torque performance compared to the benchmark motor within the same input current and armature winding specifications. These findings demonstrate the effectiveness of the proposed design and its potential for improving end-wingding utilization and torque performance in electric machines.

Developing a rapid and quantitative method to accurately evaluate the physiological abilities of living cells is critical for tumor control. Many experiments have been conducted in the field of biology in an attempt to measure the proliferation and movement abilities of cells, but existing methods cannot provide real-time and objective data for label-free cells. The quantitative imaging technique, including an automatic segmentation algorithm for individual label-free cells, has been a breakthrough in this regard. In this study, we develop a combined automatic image processing algorithm of CellPose and watershed segmentation for the long-term and real-time imaging of label-free cells. This method shows strong reliability in cell identification regardless of cell densities, allowing us to obtain accurate information about the number and proliferation ability of the target cells. Additionally, our results also suggest that this method is a reliable way to assess real-time data on drug cytotoxicity, cell morphology, and cell movement ability.

Supervised learning methods excel in traditional relation extraction tasks. However, the quality and scale of the training data heavily influence their performance. Few-shot relation extraction is gradually becoming a research hotspot whose objective is to learn and extract semantic relationships between entities with only a limited number of annotated samples. In recent years, numerous studies have employed prototypical networks for few-shot relation extraction. However, these methods often suffer from overfitting of the relation classes, making it challenging to generalize effectively to new relationships. Therefore, this paper seeks to utilize a diffusion model for data augmentation to address the overfitting issue of prototypical networks. We propose a diffusion model-enhanced prototypical network framework. Specifically, we design and train a controllable conditional relation generation diffusion model on the relation extraction dataset, which can generate the corresponding instance representation according to the relation description. Building upon the trained diffusion model, we further present a pseudo-sample-enhanced prototypical network, which is able to provide more accurate representations for prototype classes, thereby alleviating overfitting and better generalizing to unseen relation classes. Additionally, we introduce a pseudo-sample-aware attention mechanism to enhance the model’s adaptability to pseudo-sample data through a cross-entropy loss, further improving the model’s performance. A series of experiments are conducted to prove our method’s effectiveness. The results indicate that our proposed approach significantly outperforms existing methods, particularly in low-resource one-shot environments. Further ablation analyses underscore the necessity of each module in the model. As far as we know, this is the first research to employ a diffusion model for enhancing the prototypical network through data augmentation in few-shot relation extraction.

Recent years have seen a rise in interest in document-level relation extraction, which is defined as extracting all relations between entities in multiple sentences of a document. Typically, there are multiple mentions corresponding to a single entity in this context. Previous research predominantly employed a holistic representation for each entity to predict relations, but this approach often overlooks valuable information contained in fine-grained entity mentions. We contend that relation prediction and inference should be grounded in specific entity mentions rather than abstract entity concepts. To address this, our paper proposes a two-stage mention-level framework based on an enhanced heterogeneous graph attention network for document-level relation extraction. Our framework employs two different strategies to model intra-sentential and inter-sentential relations between fine-grained entity mentions, yielding local mention representations for intra-sentential relation prediction and global mention representations for inter-sentential relation prediction. For inter-sentential relation prediction and inference, we propose an enhanced heterogeneous graph attention network to better model the long-distance semantic relationships and design an entity-coreference path-based inference strategy to conduct relation inference. Moreover, we introduce a novel cross-entropy-based multilabel focal loss function to address the class imbalance problem and multilabel prediction simultaneously. Comprehensive experiments have been conducted to verify the effectiveness of our framework. Experimental results show that our approach significantly outperforms the existing methods.

In this study, we aim to investigate the effect of different reconstruction techniques on computer-aided system (CAD) pulmonary nodules in low-dose CT. A prospective collection of 380 patients with low-dose chest CT pulmonary nodules was performed. Filtered back projection, quantum noise reduction, 3D adaptive iteration, and cloud iterative techniques were used to reconstruct the original data. The average signal-to-noise ratio (SNR) of each technique was measured. Compared with the contrast-to-noise ratio (CNR), we analyzed the sensitivity and false-positive number of the lung nodules by CAD in each group of techniques. The SNR and CNR are sequentially improved according to the filtered back projection, quantum noise reduction, three-dimensional adaptive iteration, and cloud iterative technique (P

The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells are critical in glucose homeostasis. Here the authors show that the Ca2+ oscillations of α and β cells are phase-locked, and that the oscillation pattern is tuned by paracrine interactions between α and β cells.

Abstract Drug resistance is responsible for castration-resistant prostate cancer (CRPC)-associated mortality. While ATP binding cassette subfamily C member 5 (ABCC5) has been reported to regulate multiple drug resistance, its drug-efflux function may not be the main reason underlying resistance to enzalutamide, an androgen receptor inhibitor. Here, we aimed to determine whether the non-drug efflux function of ABCC5 affects enzalutamide resistance. The ABCC5 expression data in patients with prostate cancer (PCa) were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus, and their correlation with disease prognosis was analyzed. Immunohistochemical staining was performed on a cohort of 80 patient samples. Proliferation of enzalutamide-resistant 22RV1 and C4-2B cells was investigated using CCK-8, EdU, and colony formation assays. The effect of ABCC5 silencing on enzalutamide resensitization was evaluated in vitro and in vivo. Functional assays indicated that ABCC5 depletion resensitized enzalutamide-resistant cells to inhibit cell growth and impeded xenograft tumor proliferation. Mechanistically, luciferase and ChIP assays confirmed that P65 regulated AR expression and activity by binding to its promoter, while ABCC5-mediated resistance effected by AR-V7 (one of the widely studied AR splicing variants that meditate AR antagonist resistance) upregulation could be reversed by P65 knockdown. Furthermore, activation of the NF-κB pathway reversed the effects of ABCC5 knockdown by extra AR-V7 expression. Thus, ABCC5 might be a novel target for enzalutamide-resistant CRPC treatment.

Abstract Oncogene-induced tumorigenesis results in the variation of epigenetic modifications, and in addition to promoting cell immortalization, cancer cells undergo more intense cellular stress than normal cells and depend on other support genes for survival. Chromosomal translocations of mixed-lineage leukemia (MLL) induce aggressive leukemias with an inferior prognosis. Unfortunately, most MLL-rearranged (MLL-r) leukemias are resistant to conventional chemotherapies. Here, we showed that hydroxyurea (HU) could kill MLL-r acute myeloid leukemia (AML) cells through the necroptosis process. HU target these cells by matrix metallopeptidase 2 (MMP2) deficiency rather than subordinate ribonucleotide reductase regulatory subunit M2 (RRM2) inhibition, where MLL directly regulates MMP2 expression and is decreased in most MLL-r AMLs. Moreover, iron chelation of HU is also indispensable for inducing cell stress, and MMP2 is the support factor to protect cells from death. Our preliminary study indicates that MMP2 might play a role in the nonsense-mediated mRNA decay pathway that prevents activation of unfolding protein response under innocuous endoplasmic reticulum stress. Hence, these results reveal a possible strategy of HU application in MLL-r AML treatment and shed new light upon HU repurposing.

BackgroundEsophageal cancer is one of the deadliest malignancies in the world, and 5-year overall survival (OS) of esophageal cancer ranges from 12% to 20%. Surgical resection remains the principal treatment. The American Joint Commission on Cancer (AJCC) TNM (tumor, node, and metastasis) staging system is a key guideline for prognosis and treatment decisions, but it cannot fully predict outcomes. Therefore, targeting the molecular and biological features of each patient’s tumor, and identifying key prognostic biomarkers as effective survival predictors and therapeutic targets are highly important to clinicians and patients.MethodsIn this study, three different methods, including Univariate Cox regression, Lasso regression, and Randomforest regression were used to screen the independent factors affecting the prognosis of esophageal squamous cell carcinoma and construct a nomogram prognostic model. The accuracy of the model was verified by comparing with TNM staging system and the reliability of the model was verified by internal cross validation.ResultsPreoperative neutrophil lymphocyte ratio(preNLR), N-stage, p53 level and tumor diameter were selected to construct the new prognostic model. Patients with higher preNLR level, higher N-stage, lower p53 level and larger tumor diameter had worse OS. The results of C-index, Decision Curve Analysis (DCA), and integrated discrimination improvement (IDI) showed that the new prognostic model has a better prediction than the TNM staging system.ConclusionThe accuracy and reliability of the nomogram prognostic model were higher than that of TNM staging system. It can effectively predict individual OS and provide theoretical basis for clinical decision making.

Pea is a conventional grain-feed-grass crop in Tibet and the only high-protein legume in the region; therefore, it plays an important role in Tibetan food and grass security. Zinc finger-homeodomain (ZF-HD) belongs to a family of homozygous heterotypic cassette genes, which play an important role in plant growth, development, and response to adversity stress. Using a bioinformatics approach, 18 PsZF-HD family members were identified. These genes were distributed across seven chromosomes and two scaffold fragments, and evolutionary analysis classified them into two subgroups, MIF and ZHD. The MIF subgroup was subdivided into three subclasses (PsMIFⅠ–III), and the ZHD subgroup was subdivided into five subclasses (ZHDⅠ–V). The PsZF-HD members were named PsMIF1–PsMIF4 and PsZHD1–PsZHD14. Twelve conserved motifs and four conserved domains were identified from PsZF-HD family, of which MIF subgroup only contained one domain, while ZHD subgroup contained two types of domains. In addition, there were significant differences in the three-dimensional structures of the protein members of the two subgroups. Most PsZF-HD genes had no introns (13/18), and only five genes had one intron. Forty-five cis-acting elements were predicted and screened, involving four categories: light response, stress, hormone, and growth and development. Transcriptome analysis of different tissues during pea growth and development showed that PsZHD11, 8, 13, 14 and MIF4 were not expressed or were individually expressed in low amounts in the tissues, while the other 13 PsZF-HDs genes were differentially expressed and showed tissue preference, as seen in aboveground reproductive organs, where PsZHD6, 2, 10 and MIF1 (except immature seeds) were highly expressed. In the aerial vegetative organs, PsZHD6, 1, and 10 were significantly overexpressed, while in the underground root system, PsMIF3 was specifically overexpressed. The leaf transcriptome under a low-nitrogen environment showed that the expression levels of 17 PsZF-HDs members were upregulated in shoot organs. The leaf transcriptome analysis under a low-temperature environment showed stress-induced upregulation of PsZHD10 and one genes and down-regulation of PsZHD6 gene. These results laid the foundation for deeper exploration of the functions of the PsZF-HD genes and also improved the reference for molecular breeding for stress resistance in peas.

As a new type of flexible regulation resource, energy storage systems not only smooth out the fluctuation of new energy generation but also track the generation scheduling combined with new energy power to enhance the reliability of new energy system operations. In recent years, installing energy storage for new on-grid energy power stations has become a basic requirement in China, but there is still a lack of relevant assessment strategies and techno-economic evaluation of the size determination of energy storage systems from the perspective of new energy power stations. Therefore, this paper starts from summarizing the role and configuration method of energy storage in new energy power stations and then proposes multidimensional evaluation indicators, including the solar curtailment rate, forecasting accuracy, and economics, which are taken as the optimization targets for configuring energy storage systems in PV power stations. Lastly, taking the operational data of a 4000 MWPV plant in Belgium, for example, we develop six scenarios with different ratios of energy storage capacity and further explore the impact of energy storage size on the solar curtailment rate, PV curtailment power, and economics. The method proposed in this paper is effective for the performance evaluation of large PV power stations with annual operating data, realizes the automatic analysis on the optimal size determination of energy storage system for PV power stations, and verifies the rationality of the principle for configuring energy storage for PV power stations in some regions of China.

IntroductionObesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive.MethodsWe performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG.ResultsCompared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro. Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro. Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway.ConclusionThe downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.

ObjectiveTo investigate the effects of sleeve gastrectomy (SG) on diabetes-related cognitive decline (DCD) in rats with diabetic mellitus (DM).Methods and methodsForty Wistar rats were randomly divided into control (CON) group (n=10), diabetes mellitus (DM) group (n=10), sham operation (SHAM) group (n=10) and SG group (n=10). DM model was established by high-fat diet (HFD) combined with intraperitoneal injection of streptozocin (STZ). Behavioral evaluation was given using Morris water maze test and Y-maze. In addition, PET-CT, TUNEL assay, histological analysis, transmission electron microscopy (TEM), immunohistochemistry (IHC) and Western blot analysis were used to evaluate the alleviating effects and potential mechanisms of SG on DCD in DM rats.ResultsCompared with the sham group, SG induced significant improvement in the metabolic indices such as blood glucose and body weight. Besides, it could attenuate the insulin resistance compared with SHAM group. In addition, SG could improve the cognitive function of DM rats, which were featured by significant decrease in the escape latency (P

ObjectiveTo identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection.MethodsSerum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone.ResultsTRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram.ConclusionWe suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.

The development of global energy internet (GEI) poses greater challenges to long-distance power energy supply and demand balance and sustainable supply reliability. Different types of energy storage technologies are the preferred means to solve the power and electricity balance, which are essential parts of GEI development. The requirements and configuring of energy storage are closely related to the characteristics and goals of specific application scenarios. Through literature research and demonstration projects, the configuration methods and performance requirements of energy storage technologies in three typical application scenarios of GEI were analyzed. The suggestions on energy storage types, power of energy storage configuration and discharge time range suitable for different applications were given. Aiming at the characteristics of large-scale clean energy and long-distance transmission of the GEI, a specific energy storage access topology was proposed, which provided a solution for the functional verification of simulated energy storage access to GEI applications.

Chemoresistance against 5-fluorouracil (5-FU) is a major issue for colorectal cancer (CRC) patients. Increasing evidence for the roles of CD147 in glycolipid metabolic reprogramming and chemoresistance of tumor cells has emerged in recent years. However, whether CD147 contributes to 5-FU resistance in CRC and the role of abnormal glycolipid metabolism in this process remain poorly understood. We analyzed CD147 expression in primary tumor samples of CRC patients and found that upregulated CD147 correlated with decreased 5-FU chemosensitivity and an unfavorable prognosis of CRC patients. Moreover, in vivo and in vitro experiments confirmed that CD147 regulates glycolipid metabolism through two separate pathways. Mechanistically, CD147 upregulates HIF-1α-mediated glycolysis by activating the PI3K/AKT/mTOR pathway and CD147 also attenuates PPARα-mediated fatty acid oxidation by activation of the MAPK pathway. Most importantly, we found that CD147 confers 5-FU resistance in CRC via these glycolipid metabolic signatures. Our results demonstrated that CD147 is a potential 5-FU resistance biomarker for CRC patients and a candidate therapeutic target to restore 5-FU sensitivity of 5-FU-resistant CRC by remodeling glycolipid metabolism.

AbstractWith the development of high-pressure and high-temperature condensate gas wells, the wellbore blockage problems have become increasingly serious. Hence, selecting appropriate treatment technology plays a crucial role in solving the wellbore blockage problems. This study presents a comprehensive literature review on understanding the blockage type, mechanism, and treatment of the high-temperature and high-pressure condensate gas wells. The causes, endangerments, mechanisms, influences, and preventive technologies of the 4 wellbore blockage types are presented. The significant aspects of the treatment technology, such as the principle, type, advantage and disadvantage, adaptability, limitation, and future research direction of the treatment technologies, are thoroughly discussed. The breakthrough solid autogenetic heat treatment technology has been selected to remove hydrate blockage. The present review highlights the current state in the industry, future position, and strategies for the researchers to follow. Finally, the advantages and disadvantages and future research directions of specific treatment technology are presented on the removing effect, cost, and environmental aspects.

Abstract Background Hexokinase domain component 1 (HKDC1) plays an oncogenic role in certain types of cancer, such as lymphoma, liver cancer, and breast cancer. Previous bioinformatics study revealed that HKDC1 was significantly upregulated in lung adenocarcinoma (LUAD). However, its biological functions and potential mechanism in LUAD have not been studied. Methods We performed bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and a series of functional assays in vitro and in vivo to investigate the roles of HKDC1 in LUAD. Results We discovered that HKDC1 was highly expressed in LUAD tissues and cell lines, and the positive expression of HKDC1 was correlated with aberrant clinicopathological characteristics in LUAD patients. Furthermore, HKDC1 could serve as a prognostic predictor for LUAD patients. Overexpression of HKDC1 promoted proliferation, migration, invasion, glycolysis, EMT and tumorigenicity, whereas knockdown of HKDC1 produced the opposite functional effects. Mechanistically, HKDC1 could regulate the AMPK/mTOR signaling pathway to perform its biological function. Conclusions Our findings suggest that HKDC1 plays an oncogenic role in LUAD. Targeting this gene may provide a promising therapeutic target to delay LUAD progression.

Abstract Background Esophageal squamous cell carcinoma with tumor thrombus in the arch of the azygos vein has not been reported to date. Neoadjuvant chemotherapy can decrease the stage in patients with advanced preoperative tumor staging, regaining surgical opportunities and significantly prolonging progression-free survival and overall survival. Herein, we present a case of esophageal squamous cell carcinoma accompanied by tumor thrombus in the arch of the azygos vein, and the patient underwent radical surgery after neoadjuvant chemotherapy. Case presentation A 63-year-old male with esophageal squamous cell carcinoma was found to have tumor thrombus formation in the arch of the azygos vein. Four courses of neoadjuvant chemotherapy with the TP regimen (paclitaxel plus nedaplatin) were given. Reexamination revealed a significant reduction in tumor and tumor thrombus volume. Therefore, McKeown radical resection for esophageal cancer and removal of the tumor thrombus in the arch of the azygos vein were performed. Postoperative pathology suggested complete remission of the esophageal tumor and the presence of small focal cancer tissues in the arch of the azygos vein. Conclusion We report a case of esophageal squamous cell carcinoma with tumor thrombus formation in the azygos vein. We conducted radical resection after 4 rounds of neoadjuvant chemotherapy, and the pathological results revealed complete remission of the tumor. We report our experience addressing this rare case, and we hope to find the underlying mechanism of tumor thrombus formation and whether it has any effects on prognosis in our future study.

BackgroundEarly screening of clinically significant prostate cancer (csPCa) may offer opportunities in revolutionizing the survival benefits of this lethal disease. We sought to introduce a modified prostate health index density (mPHI) model using imaging indicators and to compare its diagnostic performance for early detection of occult onset csPCa within the prostate-specific antigen (PSA) gray zone with that of PHI and PHID.Methods and ParticipationBetween August 2020 and January 2022, a training cohort of 278 patients (total PSA 4.0–10.0 ng/ml) who were scheduled for a prostate biopsy were prospectively recruited. PHI and PHID were compared with mPHI (LDTRD×APD×TPV×PHI) for the diagnosis performance in identifying csPCa. Pathology outcomes from systematic prostate biopsies were considered the gold standard.ResultsThis model was tested in a training cohort consisting of 73 csPCa, 14 non-clinically significant prostate cancer(non-csPCa), and 191 benign prostatic hyperplasia (BPH) samples. In the univariate analysis for the PSA gray zone cohort, for overall PCa, the AUC of mPHI (0.856) was higher than PHI (0.774) and PHID (0.835). For csPCa, the AUC of mPHI (0.859) also surpassed PHI (0.787) and PHID (0.825). For detection of csPCa, compared with lower specificities from PHI and PHID, mPHI performed the highest specificity (76.5%), by sparing 60.0% of unnecessary biopsies at the cost of missing 11 cases of csPCa. The mPHI outperformed PHI and PHID for overall PCa detection. In terms of csPCa, mPHI exceeds diagnostic performance with a better net benefit in decision curve analysis (DCA) compared with PHI or PHID.ConclusionsWe have developed a modified PHI density (mPHI) model that can sensitively distinguish early-stage csPCa patients within the PSA gray zone.Clinical Trial RegistrationClinicalTrials.gov, NCT04251546.

Diabetic cardiomyopathy (DCM) is characterized by impaired diastolic and systolic myocardial performance and is a major cause of morbidity and mortality in patients with diabetes. Surgical bariatric procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes (T2DM) and have benefits with myocardial function. Maintaining cardiac mitochondrial homeostasis is a promising therapeutic strategy for DCM. However, whether SG surgery affects mitochondrial function and its underlying mechanism remains unclear. This study aimed to investigate the effect of SG surgery on mitochondrial homeostasis and intracellular oxidative stress in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose and high fat-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a remarkably metabolic benefit of SG, including a reduced body weight, food intake, blood glucose levels, and restored glucose tolerance and insulin sensitivity post-operatively. Also, SG ameliorated the pathological cardiac hypertrophy, myocardial fibrosis and the dysfunction of myocardial contraction and diastole, consequently delayed the progression of DCM. Also, SG restored the mitochondrial dysfunction and fragmentation through the AMPK signaling activation mediated nuclear receptor subfamily 4 group A member 1 (NR4A1)/DRP1 suppression in vivo. H9c2 cardiomyocytes showed that activation of AMPK could reverse the mitochondrial dysfunction somehow. Collectively, our study provided evidence that SG surgery could alleviate mitochondrial dysfunction in DCM. Moreover, AMPK-activated NR4A1/DRP1 repression might act as a significant reason for maintaining mitochondrial homeostasis in the myocardium, thus contributing to morphological and functional alleviation of DCM.

Background: Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined.Methods: Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group.Results: Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway.Conclusion: These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the most difficult subtype of esophageal cancer to treat due to the paucity of effective targeted therapy. ESCC is believed to arise from cancer stem cells (CSCs) that contribute to metastasis and chemoresistance. Despite advances in diagnosis and treatment, the prognosis of ESCC patients remains poor. Methods In this study, we applied western blot, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, RNA-Seq analysis, luciferase reporter assay, Chip-qPCR, bioinformatics analysis, and a series of functional assays to show the potential role of LEF1 in regulating esophageal CSCs. Results We found that the overexpression of LEF1 was associated with aberrant clinicopathological characteristics and the poor prognosis of ESCC patients. In addition, the elevated expression of LEF1 and OV6 was significantly associated with aberrant clinicopathological features, and poor patient prognosis. Moreover, the overexpression of LEF1 was observed in esophageal CSCs purified by the magnetic sorting of adherent and spheroidal ESCC cells. The increased level of LEF1 in CSCs facilitated the expression of CSC markers, stem cell-like properties, resistance to chemotherapy, and tumorigenicity and increased the percentage of CSCs in ESCC samples. Conversely, the knockdown of LEF1 significantly diminished the self-renewal properties of ESCC. We showed that LEF1 played an important mechanical role in activating the TGF-β signaling pathway by directly binding to the ID1 gene promoter. A positive association between LEF1 and ID1 expression was also observed in clinical ESCC samples. Conclusion Our results indicate that the overexpression of LEF1 promotes a CSC-like phenotype in and the tumorigenicity of ESCC by activating the TGF-β signaling pathway. The inhibition of LEF1 might therefore be a novel therapeutic target to inactivate CSCs and inhibit tumor progression.

BackgroundLung cancer is the leading cause of death from cancer, and lung adenocarcinoma (LUAD) is the most common form. Despite the great advances that has been made in the diagnosis and treatment for LUAD, the pathogenesis of LUAD remains unclear. In this study, we aimed to identify the function of circKEAP1 derived from the exon of KEAP1 in LUAD.MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The levels and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR (qRT-PCR). Subsequently, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, the dual luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its host gene, which activated the KEAP1/NRF2 signal pathway, and finally suppresses the tumor progress. Our findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a novel method for the treatment of LUAD.

Gastric cancer (GC), characterized by uncontrolled growth, is a common malignant tumor of the digestive system. The Wnt signaling pathway plays an important role in the tumorigenesis and proliferation of GC. Many studies on this signaling pathway have focused on its intracellular regulatory mechanism, whereas little attention has been given to extracellular regulatory factors. Dickkopf-1 (Dkk1) is a secretory glycoprotein, and it can bind inhibit activation of the Wnt pathway. However, the regulation and mechanism of DKK1 in the proliferation of GC remain unclear. FOXC1 plays an important role in organ development and tumor growth, but its role in GC tumor growth remains unknown. In this study, we found that the FOXC1 is highly expressed in patients with GC and high expression of FOXC1 correlates to poor prognosis. In addition, we found that the Wnt signaling pathway in GC cells with high FOXC1 expression was strongly activated. FOXC1 negatively regulates DKK1 expression by binding to its promoter region, thereby promoting the activation of Wnt pathway. FOXC1 can also form a complex with unphosphorylated β-catenin protein in the cytoplasm and then dissociates from β-catenin in the nucleus, thereby promoting the entry of β-catenin into the nucleus and regulating expression of c-MYC, which promotes the proliferation of GC cells. Our study not only reveals the function and mechanism of FOXC1 in GC, but also provides a potential target for clinic GC treatment.

This study points out that families' support of perseverance in creative efforts will increase children's originality of creative drawing through children's persistence in information searching. Data analysis based on 134 Chinese young children's creative drawings and survey supports the above hypothesis. Moreover, children's exposure to COVID-19 pandemic positively moderates the relationship between supporting perseverance and children's search persistence, such that high exposure to COVID-19 pandemic will increase the positive relationship between support of perseverance and search persistence. And children's prosocial motivation inhibits the influence of search persistence on originality. Contributions to the theory of children's creativity are discussed.

The boom in social media with regard to producing and consuming information simultaneously implies the crucial role of online user influence in determining content popularity. In particular, understanding behavior variations between the influential elites and the mass grassroots is an important issue in communication. However, how their behavior varies across user categories and content domains and how these differences influence content popularity are rarely addressed. From a novel view of seven content domains, a detailed picture of the behavior variations among five user groups, from the views of both the elites and mass, is drawn on Weibo, one of the most popular Twitter-like services in China. Interestingly, elites post more diverse content with video links, while the mass possess retweeters of higher loyalty. According to these variations, user-oriented actions for enhancing content popularity are discussed and testified. The most surprising finding is that the diverse content does not always bring more retweets, and the mass and elites should promote content popularity by increasing their retweeter counts and loyalty, respectively. For the first time, our results demonstrate the possibility of highly individualized strategies of popularity promotions in social media, instead of a universal principle.