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Abstract Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c+ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c+ cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c+ cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.

Abstract Background Patient involvement is crucial to the success of kidney transplants. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward postoperative self-management among kidney transplant recipients. Methods A web-based cross-sectional study was conducted in Ruijin Hospital (Shanghai, China) between March 24, 2023, and April 15, 2023 in kidney transplant recipients. A questionnaire was designed to collect data about the characteristics of the participants and their KAP toward postoperative self-management. KAP scores were calculated based on participants' responses, using predefined scoring criteria tailored to evaluate each dimension of KAP effectively. Results A total of 483 valid questionnaires were collected, including 189 (39.13%) participants aged between 46 and 60 years. The mean score of knowledge, attitude and practice were 23.44 ± 4.87 (possible range: 0–28), 43.59 ± 2.65 (possible range: 10–50), 52.52 ± 4.64 (possible range: 0–58), respectively. The multivariate analysis showed knowledge scores (OR = 1.15, 95% CI = 1.10–1.20, p

Abstract Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Abstract Background This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). Methods We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal–Wallis test and Mann–Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. Results We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal–Wallis test and Mann–Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. Conclusions There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Abstract Chloroplast genomes, pivotal for understanding plant evolution, remain unexplored in Rutaceae, a family with key perennial crops like citrus. Leveraging next-generation sequencing data from 509 Rutaceae accessions across 15 species, we conducted a de novo assembly of 343 chloroplast genomes, unveiling a chloroplast variation map highlighting the heterogeneous evolution rates across genome regions. Notably, differences in chloroplast genome size primarily originate from large single-copy and small single-copy regions. Structural variants predominantly occurred in the single-copy region, with two insertions located at the single-copy and inverted repeat region boundary. Phylogenetic analysis, principal component analysis, and population genetic statistics confirmed the cohesive clustering of different Citrus species, reflecting evolutionary dynamics in Citrus diversification. Furthermore, a close chloroplast genetic affinity was revealed among Atalantia (previously regarded as primitive citrus), Clausena, and Murraya. Zanthoxylum formed a distinct group with heightened genetic diversity. Through expanding our analysis to include 34 published chloroplast genomes, we explored chloroplast gene selection, revealing divergent evolutionary trends in photosynthetic pathways. While Photosystem I and Photosystem II exhibited robust negative selection, indicating stability, the Nicotinamide adenine dinucleotide (NADH) dehydrogenase pathway demonstrated rapid evolution, which was indicative of environmental adaptation. Finally, we discussed the effects of gene length and GC content on chloroplast gene evolution. In conclusion, our study reveals the genetic characterization of chloroplast genomes during Rutaceae diversification, providing insights into the evolutionary history of this family.

Abstract Background Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. Methods C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. Results CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. Conclusions Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

The patterns of material accumulation in buildings and infrastructure accompanied by rapid urbanization offer an important, yet hitherto largely missing stock perspective for facilitating urban system engineering and informing urban resources, waste, and climate strategies. However, our existing knowledge on the patterns of built environment stocks across and particularly within cities is limited, largely owing to the lack of sufficient high spatial resolution data. This study leveraged multi-source big geodata, machine learning, and bottom-up stock accounting to characterize the built environment stocks of 50 cities in China at 500 m fine-grained levels. The per capita built environment stock of many cities (261 tonnes per capita on average) is close to that in western cities, despite considerable disparities across cities owing to their varying socioeconomic, geomorphology, and urban form characteristics. This is mainly owing to the construction boom and the building and infrastructure-driven economy of China in the past decades. China’s urban expansion tends to be more “vertical” (with high-rise buildings) than “horizontal” (with expanded road networks). It trades skylines for space, and reflects a concentration–dispersion–concentration pathway for spatialized built environment stocks development within cities in China. These results shed light on future urbanization in developing cities, inform spatial planning, and support circular and low-carbon transitions in cities.

Basalt fiber-reinforced polymer (BFRP) has high mechanical strengths as a repairing material but exhibits low ductility. This paper investigates the damage process of reinforced concrete beams repaired using BFRP sheets, aimed at understanding the underlying mechanisms of achieving structural ductility when BFRP sheets are used. The damage process was assessed using digital image correlation (DIC) and acoustic emission (AE) techniques applied to monitor surface and internal damages of three full-scale concrete beams subjected to four-point bending. A beam was first loaded to crack, then repaired with BFRP sheets, and finally reloaded to failure. Surface strain fields and cracks were monitored using a DIC method, and cracking events were monitored using AE sensors deployed at different positions of the beams. The AE signals were analyzed to assess the damage process. The test results indicated that (1) tensile cracks predominated throughout the loading process; (2) the BFRP sheets hindered the widening of cracks and promoted the generation of fine cracks; and (3) the development of concrete cracks promoted interfacial debonding at steel-concrete and BFRP-concrete interfaces. A combination of different types of cracks and interfacial debonding helped the repaired beam achieve ductile flexural behaviors.

Abstract In China, coal miners are the primary workforce in coal mining, and among all patients with occupational diseases, 90% suffer from pneumoconiosis. Therefore, the psychological problems resulting from the dual pressures of occupational stress and the high risk of occupational diseases among coal miners are significant factors that affect the development of physical and mental health and even production safety. The Crown–Crisp Experience Index (CCEI) is a multidimensional questionnaire that assesses the psychological state of patients. This study aims to test reliability and validity of Chinese version of the CCEI questionnaire using factor analysis, and apply it to coal miners. We recruited a total of 900 participants from different occupational stages in coal mining, including active miners, Coal Workers’ Pneumoconiosis (CWP) patients, and retired miners, to evaluate the reliability and validity of the Chinese version of the CCEI questionnaire. A questionnaire survey was conducted on three groups of 1000 individuals each, including active coal miners, retired coal miners, and pneumoconiosis patients, to determine the detection rate of psychological problems in each group. An analysis was performed for each group to explore the primary factors influencing anxiety. The exploratory factor analysis yielded six principal components that accounted for a total of 79.389% of variances. The confirmatory factor analysis showed that the Chi-square freedom ratio (χ 2 /df) was 1.843, the root mean square error approximation was less than 0.044, and the comparative fit index was 0.938 and Tucker–Lewis index (TLI) was 0.934. The Cronbach's alpha coefficient was 0.948, and the scale-level content validity index (S-CVI) was 0.88. Effective questionnaires were obtained from 98.5%, 96.9%, to 91.0% of pneumoconiosis patients, active miners, and retired miners, respectively, with the incidence rates of psychological problems being 21%, 35.8%, and 13.6%, respectively. Compared with retired miners, active miners showed higher levels of psychological problems in the dimensions of depressive symptoms, free-floating anxiety and somatic symptoms, whereas pneumoconiosis patients had higher levels of psychological problems in the dimensions of phobic anxiety and somatic symptoms. This study demonstrates that the Chinese version of the CCEI is highly reliable and valid and can be used as a screening tool to measure patients' anxiety and fear levels in coal minders. Miners face distinct psychological challenges at different stages and require targeted screening and interventions.

The surging accumulation of trajectory data has yielded invaluable insights into urban systems, but it has also presented challenges for data storage and management systems. In response, specialized storage systems based on non-relational databases have been developed to support large data quantities in distributed approaches. However, these systems often utilize storage by point or storage by trajectory methods, both of which have drawbacks. In this study, we evaluate the effectiveness of segmented trajectory data storage with HBase optimizations for spatio-temporal queries. We develop a prototype system that includes trajectory segmentation, serialization, and spatio-temporal indexing and apply it to taxi trajectory data in Beijing. Our findings indicate that the segmented system provides enhanced query speed and reduced memory usage compared to the Geomesa system.

Abstract Objective To identify risk factors for infection complications in patients with gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) and nodal DLBCL (N-DLBCL) during treatment, respectively. Methods Total 51 GI-DLBCL patients and 80 N-DLBCL patients were included after retrieving clinical data from a single medical center in the past ten years. Logistic regression analysis was utilized to analyze patients’ data, including baseline demographics, treatments and laboratory values, to determine independent risk factors of infection in these patients. Results Total 28 of 51 patients (54.9%) in the GI-DLBCL group and 52 of 80 patients (65%) in the N-DLBCL group were observed infection events during treatment. A multivariate logistic regression model revealed that Ann-arbor stage IV (P = 0.034; odds ratio [OR]: 10.635; 95% confidence interval [CI]: 1.152-142.712), extra-nodal lesions ≥ 2 (P = 0.041; OR: 23.116; 95%CI: 1.144-466.949) and high serum lactate dehydrogenase (LDH) at the time of diagnosis (LDH > 252U/L; P = 0.033; OR: 6.058; 95%CI: 1.159–31.659) were independent risk factors for the development of infection in patients with GI-DLBCL after systemic treatment. In the N-DLBCL group, high serum C-reactive protein (CRP) (P = 0.027; OR: 1.104; 95%CI: 1.011–1.204) and a low platelet count (P = 0.041; OR: 0.991; 95%CI: 0.982-1.000) at routine blood tests just before infection occurred were identified as significant risk factors related to infection events during treatment. Conclusions Discordant independent risk factors induced infection may be present during the treatment in patients with GI-DLBCL and N-DLBCL. Close monitoring these risk factors is likely an effective strategy to prevent microbial infections in these patients.

Abstract Increasing evidence suggests that chronic inflammation plays an important role in the pathogenesis of age-related macular degeneration (AMD); however, the precise pathogenic stressors and sensors, and their impact on disease progression remain unclear. Several studies have demonstrated that type I interferon (IFN) response is activated in the retinal pigment epithelium (RPE) of AMD patients. Previously, we demonstrated that human RPE cells can initiate RNA-mediated type I IFN responses through RIG-I, yet are unable to directly sense and respond to DNA. In this study, we utilized a co-culture system combining primary human macrophage and iPS-derived RPE to study how each cell type responds to nucleic acids challenges and their effect on RPE barrier function in a homotypic and heterotypic manner. We find that DNA-induced macrophage activation induces an IFN response in the RPE, and compromises RPE barrier function via tight-junction remodeling. Investigation of the secreted cytokines responsible for RPE dysfunction following DNA-induced macrophages activation indicates that neutralization of macrophage-secreted TNFα, but not IFNβ, is sufficient to rescue RPE morphology and barrier function. Our data reveals a novel mechanism of intercellular communication by which DNA induces RPE dysfunction via macrophage-secreted TNFa, highlighting the complexity and potential pathological relevance of RPE and macrophage interactions.

The retinal pigment epithelium (RPE) is essential to maintain retinal function, and RPE cell death represents a key pathogenic stage in the progression of several blinding ocular diseases, including age-related macular degeneration (AMD). To identify pathways and compounds able to prevent RPE cell death, we developed a phenotypic screening pipeline utilizing a compound library and high-throughput screening compatible assays on the human RPE cell line, ARPE-19, in response to different disease relevant cytotoxic stimuli. We show that the metabolic by-product of the visual cycle all-trans-retinal (atRAL) induces RPE apoptosis, while the lipid peroxidation by-product 4-hydroxynonenal (4-HNE) promotes necrotic cell death. Using these distinct stimuli for screening, we identified agonists of the aryl hydrocarbon receptor (AhR) as a consensus target able to prevent both atRAL mediated apoptosis and 4-HNE-induced necrotic cell death. This works serves as a framework for future studies dedicated to screening for inhibitors of cell death, as well as support for the discussion of AhR agonism in RPE pathology.

BackgroundWhile dietary factors have shown an association with Parkinson’s disease (PD), the available data remains a subject of ongoing debate and controversy.AimWe sought to evaluate potential relationships between dietary consumption of nutrients and micronutrients and risk of PD in a large sample.MethodsCross-sectional data were retrospectively analyzed for 10,651 adults aged 40–80 years that had been collected in the US between 2007 and 2016 as a component of the nationwide National Health and Nutrition Examination Survey. Aspects of dietary intake were compared between those who reported having specific PD medication regimens or not when they completed the survey, and potential associations between diet and risk of PD were explored using binomial logistic regression. We employed Propensity Score Matching (PSM) to minimize the impact of potential confounding factors, thus enhancing the reliability of the results. Additionally, subgroup analysis based on gender and age was conducted to investigate these relationships.ResultsHigher dietary intake of iron was linked to greater PD risk [odds ratio (OR) 1.065, 95% confidence interval (CI) 1.019–1.114, p = 0.006], whereas risk decreased with higher intake of vitamin K (OR 0.999, 95% CI 0.998–1.000, p = 0.024) or vitamin C (OR 0.998, 95% CI 0.996–0.999, p = 0.039). Even after applying PSM, the connection between dietary iron intake and dietary vitamin C intake with PD risk remained substantial. Subgroup analysis results revealed a significant positive association between dietary intake of iron from food and the PD risk, which was evident among individuals under 60 years of age and among males.ConclusionThe intake of micronutrients can influence risk of PD, which should be verified and explored further in prospective samples with other dietary habits and ethnic backgrounds.

Machine learning has exhibited high efficiency in designing concrete. However, collecting the dataset for training machine learning models is challenging. To address this challenge, this paper develops an approach to collect concrete design data automatically based on information extraction techniques. The approach enables machine learning models to automatically track, extract, and learn knowledge embedded in data from relevant publications. The approach has been incorporated into AI-assisted design of low-carbon cost-effective ultra-high-performance concrete (UHPC) via integrating the capabilities of automatically collecting and processing data, predicting UHPC properties, and optimizing UHPC properties regarding the material cost, carbon footprint, and compressive strength. A self-updating mechanism is imparted to continuously learn available data. Such a mechanism enables the self-updatable automatic discovery of low-carbon cost-effective UHPC. The results showed increasing prediction accuracy and optimization performance of the proposed approach over time when more knowledge was learned from new data, therefore accelerating the design of UHPC.

Abstract Renal cancer is a common malignancy of the urinary system, and renal clear cell carcinoma (RCCC) is the most common pathological type. Transmembrane channel-like (TMC) protein is an evolutionarily conserved gene family containing 8 members, however there is still a lack of comprehensive analysis about TMC family members in RCCC. In this study, we analyzed the expression of TMC family members in RCCC from TCGA and investigated the prognosis values and immune infiltration of TMC family members in RCCC. We found that TMC2, TMC3, TMC5, TMC7 and TMC8 were significantly related with overall survival (OS) of RCCC patients. TMC3, TMC6, and TMC8 was positively correlated with the degree of immune infiltration in RCCC. TMC2, TMC6, TMC7, and TMC8 were positively correlated with immune checkpoint genes, whereas TMC4 was negative. According to KEGG and GO analysis, almost all TMCs except TMC4 were involved in the immune response. Thus, we may regard the TMC family members as novel biomarkers to predict potential prognosis and immunotherapeutic response in RCCC patients.

Objective To summarize the clinical and imaging features of patients with posterior cortical atrophy (PCA). Methods and Results Five patients with PCA admitted in West China Hospital, Sichuan University from April to June 2021 were included. All of them showed spatial perception disorder, simultaneous agnosia, miscalculation, agraphia, structural apraxia, environmental agnosia. Apraxia of dressing and agnosia of left and right were found in 3 cases. One case had facial agnosia, visual ataxia and object perception disorder. Cerebrospinal fluid (CSF) biomarker determination: amyloid β⁃protein 42 (Aβ42) decreased in 3 cases, the ratio of Aβ42/amyloid β⁃protein 40 (Aβ40) decreased significantly in 2 cases, the content of total tau protein (t ⁃ tau) increased in all 5 cases, phosphorylated tau 181 protein (p ⁃ tau181) increased in 3 cases. Neuropsychological tests showed that: 1) Five patients all had different degrees of cognitive dysfunction and impairment of activities of daily living, as well as impairment of visuospatial ability, visual memory and attention. 2) Three cases had anxiety and depression, language and executive function were impaired in 3 cases, and verbal memory was impaired in 2 cases. Head MRI examination all indicated different degrees of parieto ⁃ occipital ⁃temporal cortical atrophy. Hypometabolism in posterior regions involving parietal and temporal cortex was observed in one case with 18F⁃FDG PET. Three cases completed the visual field examination, including 5 cases of binocular vision loss, one case of complete visual field defect, 2 cases of partial visual field defect. Except one case lost to follow⁃up, other 4 cases were followed up for 20-22 months. Two cases of cognitive function, visuospatical ability decline, of which one case could not take care of themselves most of the life. Cognitive function and visuospatial ability improved in one case. There was no significant change in cognitive function and visuospatial ability in one case. Conclusions PCA should be considered in patients with relatively early⁃onset of agnosia, visual field defect and visuospatial impairment. Comprehensive neuropsychological tests related to visual function, brain MRI, 18F⁃FDG PET and CSF biomarkers would be helpful for accurate diagnosis.

Abstract In China, among all patients with occupational diseases, 90% have pneumoconiosis. The disease, which leads to psychological problems, seriously affects patients’ lives. The Crown-Crisp Experience Index (CCEI) is a multidimensional questionnaire to assess patients’ psychological conditions. Yet there is no Chinese version of CCEI. This study, therefore, aims to develop a Chinese CCEI, in line with standard localization procedures, by translating, back-translating, and culturally adapting the original English version. The final Chinese version comprises 47 items in six dimensions. The reliability and validity of the Chinese CCEI were tested by analyzing the data collected from 1,000 pneumoconiosis patients from an occupational disease prevention and treatment hospital. A rank sum test was carried out to compare the phobic anxiety (PHO) between pneumoconiosis patients and retired miners. The results of exploratory factor analysis show six principal components, which explain a total of 78.246% variances. Confirmatory factor analysis shows that the Chi-square freedom ratio (χ 2 /df) were less than 3, the root mean square error approximation (RMSEA) were less than 0.05, comparative fit Index(CFI) and incremental fit index (IFI) were greater than 0.9, average variance extracted(AVE) in six dimensions were less than 0.5, residual variances(CR) were greater than 0.8, Cronbach’s alpha coefficient 0.839, Omega ω coefficient 0.889, and S-CVI 0.88. The PHO of pneumoconiosis patients was significantly higher than that of retired miners exemplified by a statistical difference (P

Abstract High-performance fiber-reinforced cementitious composites (HPFRCC) exhibit benefits in improving infrastructure resilience but often compromise sustainability due to the higher upfront cost and carbon footprint compared with conventional concrete. This paper presents a framework to improve bridge resilience and sustainability through optimizing HPFRCC. This research considers ultra-high-performance concrete and strain-hardening cementitious composite, both featuring high mechanical strengths, ductility, and damage tolerance. This paper establishes links between bridge resilience, bridge sustainability, mechanical properties of HPFRCC, and mixture design. The investigated mechanical properties include the first crack stress, the ultimate tensile strength, and the ultimate tensile strain. With the established links, sustainability is maximized while resilience is retained by optimizing HPFRCC mixtures. The framework is implemented into a case study of a bridge that collapsed during construction. Results show that use of HPFRCC enhances resilience, and HPFRCC mixtures can be engineered to minimize the material cost and carbon footprint while retaining high resilience.

Polysaccharide of Tetrastigma hemsleyanum (THP) exert antioxidant, antibacterial, lipid-lowering, and anti-inflammatory properties, especially some evidences have highlighted the efficiency of it as an anti-tumor agent. However, as a biological macromolecule with bidirectional immune regulation, the immunological enhancement effects of THP on macrophages and its underlying mechanisms are still largely unknown. In the present study, THP was prepared and characterized, and then the effect of THP on Raw264.7 cell activation was investigated. Structural characteristics of THP showed that the average molecular weight was 370.26 kDa, and the main monosaccharide composition was galactose, glucuronic acid, mannose, and glucose at a ratio of 31.56: 25.15: 19.44: 12.60, with high viscosity causing by relative high uronic acid. For immunomodulatory activity investigation, THP promoted the production of NO, IL-6 and TNF-α, as well as the expression of IL-1β, MCP-1, iNOS and COX-2, which were almost completely inhibited by TLR4 antagonist. Further study showed that THP could activate NF-κB and MAPK signaling pathways, and thus enhanced the phagocytic activity of Raw264.7 macrophages. In conclusion, the present study provided evidences that THP could be served as a new immunomodulator in both functional foods and the pharmaceutical field.

Abstract Metabolic remodeling is the fundamental molecular feature of malignant tumors. Cancer cells require sufficient energy supplies supporting their high proliferative rate. MTHFD2, a mitochondrial one-carbon metabolic enzyme, is dysregulated in several malignancies and may serve as a promising therapeutic candidate in cancer treatment. Here, our data confirmed that MTHFD2 gene and protein was upregulated in the cancerous tissues of LUAD patients and was correlated with a poor survival in LUAD. MTHFD2 was involved in lung cancer cell proliferation, migration, and apoptosis by mediating its downstream molecules, such as DNA helicases (MCM4 and MCM7), as well as ZEB1, Vimentin and SNAI1, which contributed to tumor cell growth and epithelial-to-mesenchymal transition (EMT) process. Moreover, we identified that miRNA-99a-3p appeared to be an upstream mediator directly regulating MTHFD2 and MCM4 expression. Moreover, specific inhibition of MTHFD2 functions by siRNA or a chemical compound, improved anti-tumor sensitivities induced by pemetrexed in LUAD. Taken together, our study revealed the underlying molecular mechanisms of MTHFD2 in regulating cell proliferation and identified a novel therapeutic strategy improving the treatment efficacies in LUAD.

Large-scale and dynamic surface water mapping is crucial for understanding the impact of global climate change and human activities on the distribution of surface water resources. Remote sensing imagery has become the primary data source for surface water mapping due to its high spatiotemporal resolution and wide coverage. However, the reliability of current water products during flood seasons is limited due to the influence of clouds on optical remote sensing images. Moreover, annual and seasonal surface water mapping cannot capture intra-month variations of water bodies. To address these challenges, we proposed a high spatiotemporal surface water mapping framework on Google Earth Engine that combines multi-source remote sensing data. Our framework can generate 10 m spatial resolution surface water maps at a 15-day time step. We classified water bodies using Sentinel-2 images and a classification tree algorithm, and then used Sentinel-1 data to compensate for cloudy and missing data areas in Sentinel-2 images, resulting in seamless cloud-unaffected surface water maps. We evaluated the effectiveness of our proposed framework in six floodplains around the world, and experimental results demonstrate that the water maps generated by our framework outperform existing public datasets and our framework has great potential for hydrological applications. Our proposed framework can capture the details of surface water dynamics with higher spatial and temporal resolution and is free from cloud influence, which is necessary for water resources management, flood monitoring, and disaster response.