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A typical heterogeneous structure with ultrafine grains embedded in coarse grains is obtained by partial recrystallization annealing, which exhibits excellent cryogenic mechanical properties. Researches reveal that the hard domains, high-density GND pile-ups, and multi-axial stress states of heterogeneous structures provide nucleation positions and critical stresses for triggering twinning, meanwhile, nanotwins can refine the hard domain grains to improve the heterogeneity of heterogeneous structures during cryogenic plastic deformation. Therefore, the heterostructure-twinning interaction is identified as the key factor in realizing the excellent cryogenic strength-ductility synergy of the heterostructured CoCrFeMnNi high-entropy alloy. Besides, the nucleation and propagation of generous microcracks at single-order twin boundaries induced by the excellent twinning activity result in the rapid fracture of the heterostructured samples, whereas the microcracks can hardly be observed nearby high-order nanotwins, which indicates that generating more high-order nanotwins is a promising guiding scheme to prepare the heterostructured materials with superior cryogenic mechanical properties.

The steel/copper bimetallic structures inherit both the excellent thermal/electrical conductivity of copper alloys and the mechanical strength of steel, making it valuable for applications in heat exchangers, injection molds and the power industry. Laser powder bed fusion (LPBF) is a promising manufacturing method for the fabrication of steel/copper bimetallic structures, but the inhomogeneous heterogeneous interfaces still need to be subsequently processed to further enhance their mechanical properties. In this investigation, an attempt was made to optimize the interfacial microstructure of steel/copper bimetallic structures fabricated by the LPBF process through annealing treatment to improve their interfacial strength. As a result, the annealing treatment increased the interfacial bonding strength of the steel/copper bimetallic structure by 28% and without reducing the elongation. This is attributed to the elemental homogenization and internal stress release during heat treatment, as well as the mechanically interlocked structure of fine crystals embedded in coarse crystals formed by Cu/Fe interdiffusion at the boundary of the steel/fusion zone. However, no significant phase transitions were identified in the heterogeneous interface. A suitable heat treatment process can diffusely distribute the Cu/Fe immiscible phase and maintain fine grains. This work discusses in detail the microstructure evolution under different annealing treatments as well as the underlying mechanisms for the improvement of mechanical properties, providing a simple and effective method for post-treatment reinforcing the heterogeneous interface of 316L/CuSn10 bimetallic structure fabricated by LPBF.

The small modular PWR (SMPWR) usually adopts integral design. Under severe accident, the system responses are different from those large PWRs. It is necessary to study the severe accident behavior of the SMPWR. A MELCOR model is developed for SMPWR and its steady-state results are in good agreement with the design values. Severe accidents induced by secondary pipeline break accidents are simulated, and no pressure relief measures are taken to keep the primary loop under high pressure. The mitigation effects of passive containment air cooling system (PAS) and passive cavity injection system (PCIS) are evaluated under different cases. The results show that under high pressure conditions, PCIS can effectively cool the lower head. The earlier the PCIS operates, the more significant the mitigation effect can be. In addition, PAS can effectively reduce the peak pressure and temperature in the containment. This study can provide a reference for the formulation of severe accident management guidelines on SMPWRs.

Background: Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies. Methods: Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy. Results: Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy. Conclusions: Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy.

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects, resulting in radiation-induced skin injury (RSI). Premature cellular senescence, caused by oxidative stress and/or DNA damage from chemical or physical agents, leads to the decrease of cellular proliferation and physiological function. Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury. Atopic dermatitis and RSI have similar inflammatory symptoms. The treatment of tacrolimus (TAC) in atopic dermatitis may be associated with premature cellular senescence. TAC can prevent the onset of cellular senescence by inactivating the p38 mitogen-activated protein kinase (p38 ​MAPK). The activation of p38 ​MAPK can induce the senescence-associated secretory phenotype (SASP) by enhancing the transcriptional activity of nuclear factor kappa-B (NF-κB), which ultimately leads to premature cellular senescence. FK506 binding protein 51 (FKBP51) exhibits resistance to ionizing radiation, but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study. This review discusses the mechanism of cellular senescence in RSI and the role of TAC in both dermatitis and RSI.

Urban form contributes to crime prevention. However, most studies not only simplify the relationship between urban form and crime, they also fail to reflect the geographic structure of urban areas. This study first measured a comprehensive multidimensional urban form indicator for 1486 counties in the United States, which was used to characterize the size and geospatial structure of urban areas. Specifically, it described urban form as consisting of three components: 1) size and population distribution; 2) built environment; and 3) landscape environment. Then, generalized additive mixed models were then used to explore linear or nonlinear associations between urban form indicators and different crime types (violent and property crime). This study's main findings were that 1) the relationship between urban form and crime is not only linear but may also be nonlinear; 2) urban size, fragmentation, connectivity, forest mixing, and shrub mixing are associated with all crime types; 3) population distribution and agricultural mixing are associated with violent crime; and 4) urban patch complexity and water mixing are associated with property crime. Overall, the results of this study can provide guidance for long-term planning of urban geographic structures, contributing to the safe and sustainable development of urban areas.

Summary: Seed oil is synthesized in the embryo, which is surrounded by the seed coat. However, the genetic and molecular mechanisms of how seed coat development affects seed oil content (SOC) remains less studied. Through genome-wide association studies in Brassica napus accessions, we identify BnaA09.MYB52 transcription factor as a candidate gene underlying ZS11_qSCC.A09. Knocking out BnaMYB52 results in a 7.7%–8.2% reduction in seed coat content (SCC) but a 12.3%–13.4% increase in SOC, whereas overexpression of BnaA09.MYB52 leads to the opposite effects. Intriguingly, BnaA09.MYB52 has predominant expression in seed coat during seed development. BnaA09.MYB52 activates the expression of PMEI14 and BAN. Mutant analyses indicate that the SOC is increased by 4.3%–7.7%, while seed coat thickness shows a 12.9%–22.8% reduction in the ban and pmei14 mutants. Thus, our findings identify the molecular mechanism of MYB52-BAN/PMEI14 modules regulating SCC and SOC and provide a potential target for oil content improvement in B. napus.

Tree mycorrhizal associations have substantial consequences for soil organic carbon (SOC), but it remains unclear how nutrient availability will regulate the performance of arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) trees, and then consequently affect SOC sequestration in tropical forest soils. This study characterized the performances of AM and ECM trees, SOC content, and soil microbial functions under variable soil nitrogen (N) and phosphorus (P) content across an intact tropical rainforest based on the spatial dataset from a 60-ha dynamic plot and fitted statistical models to examine the mycorrhizal and nutrient controls on SOC stocks. ECM trees showed a better performance in soils containing higher N in total or in NH4+ forms and enhanced SOC content via increases in both species richness and basal area, which led to an increase in SOC as soil N content evaluated. AM trees had a greater basal area at N-richer (i.e., available N and NH4+) niches while a higher species richness under higher soil P levels (i.e., total and available P). The AM tree community patterns had inconsistent regulations on SOC, with basal area showing a positive while species richness exerting a negative effect on SOC content. Such counteracting effects from AM trees might attenuate SOC accumulation along the P gradient, resulting in a positive trend in SOC with soil total N:P ratios. As soil available P increased, species richness of AM trees increased, which was accompanied by a higher abundance of pathogens while a lower abundance of AM fungi. This indicated a decreased dependence of AM trees on mycorrhizal P acquisition, accompanied by the high susceptibility of roots to pathogen attacks, which may promote AM tree diversity. The performances of ECM trees were positively related to ECM fungi abundance, offering ECM trees a competitive P strategy and pathogen resistance. Summarily, our results suggest that both the basal area and species richness of mycorrhizal trees act as significant regulators for SOC sequestration along soil N or P gradient in tropical forests. Such findings provide a mechanistic understanding of soil C dynamics during vegetation changes under the rising global stoichiometric imbalance between N and P.

RAS proteins, as pivotal signal transduction molecules, are frequently mutated and hyperactivated in various human cancers, closely associated with tumor cell proliferation, survival, and metastasis. Despite extensive research on RAS targeted therapies, developing effective RAS inhibitors remains a significant challenge. Natural products, endowed with unique chemical structures and diverse biological activities through long-term natural selection, have emerged as a vital resource for discovering novel RAS-targeted therapeutic drugs. This review focuses on the latest advancements in targeting RAS with natural products and categorizes these natural products based on their mechanisms of action. Additionally, we discuss the challenges faced by these natural products during clinical translation, including issues related to pharmacokinetics. Strategies such as combination therapy, structural optimization, and drug delivery systems are anticipated to enhance efficacy and overcome these challenges.

Glacial lakes (GLs), which serve as natural reservoirs, are also prospective sources of risk, and their risk levels are continuously increasing as a result of global climate warming. Nevertheless, GLs are situated in mountainous and valley regions, which are distinguished by their complex terrain and unpredictable weather conditions. This leads to restricted availability of optical imagery as a consequence of the frequent cloud cover. Synthetic Aperture Radar (SAR), however, encounters issues with geometric distortion. This paper introduces an unsupervised method based on geometric distortion detection (without orbit state information) and historical positioning using dual-orbit SAR imagery to research GL extraction effectively. This method detects low-quality pixels from dual-orbit SAR imagery through geometric distortion. It extracts GLs using a majority voting integration of unsupervised classification algorithms constrained by historical GL center points. The Southeastern Tibetan Plateau (SETP) was chosen as a representative region for the study, and experiments were conducted from July to August 2018 using dual-orbit Sentinel-1 imagery. A total of 600 refined samples were used for comparative verification. The results demonstrate that this method is capable of reliably identifying the active and passive geometric distortions in SAR imagery. The fusion of dual-orbit SAR based on geometric distortion can effectively enhance the classification performance of remote sensing imagery and achieve the acquisition of GL water storage area during the flood season. The geometric distortion rate was reduced from 29.9% to 7.9% after fusion correction, and the accuracy, recall rate, precision, Intersection over Union (IoU), and F1-Score were 0.989, 0.900, 0.908, 0.825, and 0.904, respectively. This serves as a reference for research that investigates the mechanisms of glacier-GL-climate change.

ABSTRACT: Background: It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard. Objective: The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction. Methods: From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model. Results: Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval. Conclusions: Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.

To address the sustainability challenges of mining, nations and regions have enacted restrictive policies aimed at enhancing ecological environment quality. This study focuses on a typical open-pit lime mine in Yongdeng County, Gansu Province, as a case study to investigate the environmental changes throughout the full life cycle of the mine, from before the start of mining, through peak mining, to the final stage of ecological recovery. Employing the Remote Sensing Ecological Index (RSEI) derived from Landsat satellite imagery spanning 1990 to 2023, we conducted a comprehensive analysis utilizing the Sen + Mann-Kendall method. The results revealed that on the temporal dimension, a non-monotonic trend comprising an initial ascent, a descent, and a subsequent ascent in the ecological environment quality of the study area over the three-decade period. from a spatial perspective, the mining zone regions consistently exhibited a poor ecological state, contrasting with the generally better condition observed in non-mining regions. These results can provide reference for the ecological environment governance of open-pit mines.

Lycopi herba, a traditional Chinese medicinal plant, has long been valued for its aerial parts. however, its roots, which are often discarded as non-medicinal waste, actually contain flavonoid compounds that possess potential medicinal values such as anti-inflammatory, antioxidant, and anti-tumor activities. Despite this, studies on the extraction, purification, and biological activity assessment of total flavonoids from L. herba roots (TFLHR) remain inadequate. Our study aimed to optimize the extraction and purification processes for TFLHR and evaluate their anti-proliferative effects on human fibroblast-like synoviocytes (HFLS-RA), which are key pathological cells in rheumatoid arthritis. By utilizing ultrasound-assisted extraction combined with response surface methodology (RSM), we optimized the extraction conditions, achieving a total flavonoid content of 90.484 ± 0.974 mg/g under the optimal settings: a liquid–solid ratio of 48:1 mL/g, 13 min of ultrasound treatment, 70 % ethanol, and an extraction temperature of 43°C. Subsequently, macroporous resin chromatography was employed for flavonoid purification, with AB-8 resin exhibiting the highest performance, achieving adsorption and desorption rates of 79.64 ± 1.51 % and 88.61 ± 1.02 %, respectively. By further refining the purification conditions through RSM, the purity of flavonoids was increased to 63.9 ± 1.86 %. Through ultra performance liquid chromatography tandem-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) analysis, 74 flavonoid compounds across 15 categories were identified. Further activity studies demonstrated that purified TFLHR exhibited significant concentration-dependent anti-proliferative effects on HFLS-RA cells. This study not only provides a scientific basis for the comprehensive utilization of L. herba root resources but also highlights the potential medicinal value of TFLHR in the treatment of rheumatoid arthritis, laying a foundation for future research into its specific mechanisms and clinical applications.

Summary: Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice. Notably, AR expression in the liver of female mice is up to three times higher than that in their male littermates, accounting for the more pronounced response to glucagon in females. Mechanistically, hepatic AR promotes energy metabolism and enhances lipid breakdown for liver glucose production in response to glucagon treatment through the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/estrogen-related receptor alpha (ERRα)-mitochondria axis. Overall, our findings highlight the crucial role of hepatic AR in mediating glucagon signaling and the sexual dimorphism in hepatic glucagon sensitivity.

The association between spindle metrics and sleep architecture differs during N2 vs. N3 sleep, the underlying neural mechanism is not clearly illustrated. Here, we tested the discrepancy in spindle-related brain activation between N2 and N3 within healthy college students (dataset 1: n = 27, 59 % females, median age 23 years), using simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI). To assess the replicability of the finding, we repeated the analysis among normal adults (independent dataset 2: n = 30, 50 % females, median age 32 years). The finding from dataset 1 indicated significantly increased blood-oxygen level-dependent signal in the right middle temporal gyrus during N2 compared with N3, which was well replicated in dataset 2. Furthermore, correlation analysis was performed to explore the association between this spindle-related brain activation and N2, N3 sleep duration during EEG-fMRI. We conducted the correlation analysis in N2 and N3, respectively. The negative association between spindle-related brain activation in the right middle temporal gyrus and sleep duration was only observed in N2. Our findings emphasize the unique role of spindle-related brain activation in the right middle temporal gyrus during N2 in shortening N2 sleep duration.

Self-passivating W-11.4Cr-0.6Y (in wt.%) alloy is a plasma-facing candidate armour material in fusion power plants. In the present work, the as-sintered material, fabricated via ball milling and field-assisted sintering, was annealed at 1000 °C for varying durations to induce phase decomposition. This process leads to the transformation of the initially homogeneous microstructure into two distinct phases: the W-rich phase (αW, Cr) and the Cr-rich phase (αCr, W). Cr-rich phases preferentially form at grain boundaries, where yttrium oxides are also located, and gradually coarsen to the submicron range with increasing annealing time. The chemical compositions of both phases remain relatively stable after 75 h of annealing. The Cr content in (αW, Cr) is 18.6 at.% at 75 h and 17.8 at.% at 100 h. Compared to the as-sintered state, the 100 h-annealed material exhibits significant softening at room temperature and demonstrates increased flexural strength across all tested temperatures, but lower fracture toughness at elevated temperatures. The oxidation behavior of the 100 h-annealed material under humid air at 1000 °C reveals two stages in its TGA curve: inital growth of the inner oxide layer followed by subsequent development of the protecting chromia layer. In contrast, the as-sintered material exhibits a continuous, linear mass increase throughout the oxidation process. These findings present promising prospects of the decomposed microstructure for first wall applications.

Summary: Skilled forelimb patterning is regulated by the corticospinal tract (CST) with support from brainstem regions. When the CST is lesioned, there is a loss of forelimb function; however, if indirect pathways remain intact, rehabilitative training can facilitate recovery. Following spinal cord injury, rehabilitation is thought to enhance the reorganization and plasticity of spared supraspinal-propriospinal circuits, aiding functional recovery. This study focused on the roles of cervical propriospinal interneurons (PNs) and rubrospinal neurons (RNs) in the recovery of reaching and grasping behaviors in rats with bilateral lesions of the CST and dorsal columns at C5. The lesions resulted in a 50% decrease in pellet retrieval, which normalized over four weeks of training. Silencing PNs or RNs after recovery resulted in reduced retrieval success. Notably, silencing both pathways corresponded to greater functional loss, underscoring their parallel contributions to recovery, alongside evidence of CST fiber sprouting in the spinal cord and red nucleus.

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO2 nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses. Specifically, the systemic circulation and tumoral accumulation of Cu, causing irreversible cuproptosis, work in conjunction with Mn2+, resulting in the repolarization of tumor-associated macrophages (TAMs) and amplification of the activation of the cGAS-STING pathway by damaged DNA fragments in the nucleus and mitochondria. This further stimulates antitumor immunity and ultimately reprograms the tumor microenvironment (TME) to inhibit tumor growth. Overall, ESCu@HM as a nanoreactor for cuproptosis and immunotherapy, not only improves the dual antitumor mechanism of ES and provides potential optimization for its clinical application, but also paves the way for innovative strategies for cuproptosis-mediated colorectal cancer (CRC) treatment.

Graphene and its derivatives are widely used in various fields due to their unique two-dimensional lamellar structure. This study aims to synthesize ultra-large graphene oxide (GO) sheets from natural flake graphite and investigate the factors influencing their size. Using a two-intercalation method based on the modified Hummers' method, we address the challenge of intercalating large-diameter graphene oxide by employing a secondary intercalation technique. Three different approaches were explored to control the size of the produced GO sheets. The results revealed that the completeness of the expansion graphite structure after initial intercalation significantly influenced the final GO sheet size, with more complete expansion leading to larger sheets. Optimal processing conditions were identified, involving soaking natural flake graphite in a mixed solution (H2SO4:H2O2 = 4:1), followed by drying at 60 °C for 24 h. Under these conditions, ultra-large GO sheets were predominantly monolayer with an average size of 220.99 μm and a maximum size of 438 μm. These monolayer GO sheets can be chemically reduced to graphene, making them promising for applications in transparent conductive films, optoelectronic devices, and aligned graphene composites.

Background: Identifying modifiable environmental determinants of health is important for improving the resilience of populations to infectious disease. We examined the association between residential greenspace and COVID-19 morbidity and mortality using a Danish Nationwide Cohort, and estimate the potential health benefits of greening initiatives. Methods: We followed all Danish adults aged 50 or older (N = 2,111,233) using the Danish National COVID-19 Surveillance System for COVID-19 incident infection, hospitalization and mortality, from 1 March 2020 to 26 April 2021. Greenspace was characterized using Normalized Difference Vegetation Index (NDVI) at 300x300m grid-cell level and linked to residential addresses. We used Cox regression to assess the association between greenspace and COVID-19 morbidity and mortality, and applied effect modification analyses to identify the most susceptible groups by sociodemographic status and comorbidity. Following a health impact assessment (HIA), we also estimated the preventable burden of disease attributable to greenspace under different counterfactual scenarios. Results: During an average of 14 months follow-up, 62,880 participants were infected with SARS-CoV-2, of whom 8,759 were hospitalized, and 2,382 died, with COVID-19. We observed a negative association between residential greenspace and COVID-19 morbidity and mortality, with hazard ratios (95 % confidence interval) of 0.98 (0.97, 0.99) for SARS-CoV-2 infection, 0.97 (0.94, 0.99) for COVID-19 hospitalization, and 0.96 (0.91, 1.01) for COVID-19 mortality per interquartile range (0.08 unit) increase in NDVI. Stronger associations were observed in the elderly, those with lower SES, and major chronic diseases than their corresponding groups. Regarding the HIA, we estimated that increasing greenspace around residences up to WHO recommended levels would have prevented 8–14 % of COVID-19 events during the first 14 months, with the largest benefits among those with the lowest income, education, or without employment. Conclusion: Greening initiatives in urban areas could help prevent COVID-19, and likely other infectious disease, with socially disadvantaged groups benefiting most.

The SB203580 inhibitor, a blocker of the p38MAPK pathway, has been widely studied for bioimmune applications. To investigate its immune effect of Vibrio parahaemolyticus on Pinctada fucata martensii, the key genes, PmMKK6 and PmCREB, downstream of the p38MAPK pathway were cloned, and their expression analyzed following V. parahaemolyticus infection and after a postinfection injection of SB203580 inhibitor. The effects of the SB203580 inhibitor on P. f. martensii were also determined by enzyme activity and enzyme-linked immunosorbent assay (ELISA) protein quantification, as well as liver body index and histological observation. The full-length cDNA sequences of the two genes, PmMKK6 and PmCREB, were successfully cloned. And the expression of PmMKK6 and PmCREB was upregulated at different times after injection with Vibrio parahaemolyticus and showed a significant difference compared to the VC group ( P < 0.05). Significant changes in acid phosphatase (ACP) and alkaline phosphatase (AKP) enzyme activities as well as p38 protein content were also observed (all P < 0.05). The significant changes in protein expression and activity that occurred after injection of the inhibitor were also consistent with the molecular regulatory mechanisms (P < 0.05). The hepatopancreas showed significant edema and histocellular damage after infection, with an increased mortality rate compared to the control group, whereas the edematous phenotype of the hepatopancreas was alleviated after injection of the inhibitor, and damaged cells were filled with connective tissues. Vibrio parahaemolyticus stimulation activated the immunoregulatory p38MAPK pathway in P. f. martensii, while the SB203580 inhibitor successfully blocked the p38MAPK pathway, reducing the immune response to V. parahaemolyticus and providing immunoprotection to P. f. martensii. This study therefore provides insight into the mechanism of the p38MAPK pathway in the immune response process of P. f. martensii.

Rubus fructus, the dried fruit of Rubus chingii Hu, is a versatile medicinal and edible plant. In this review, we used “Rubus chingii” or “Fupengzi” as the keyword and collected relevant information from classical Chinese herbal texts, PubMed, Web of Science, China National Knowledge Infrastructure database, and patent websites. An ethnopharmacological survey shows that R. chingii Hu belongs to a class of Rubus plants known for nourishing the kidneys and liver, consolidating essence, reducing urine, and improving vision. R. chingii is rich in flavonoids, phenolic compounds, terpenes, amino acids, and vitamins. Currently, ellagic acid and kaempferol-3-O-rutinoside are used as quality markers of R. chingii. Modern medical research indicates that it has multiple functional activities, including antioxidation/anti-aging, blood glucose regulation, immune enhancement, growth promotion, reproductive support, regulation of intestinal flora, and improvement of gastrointestinal function. Due to its numerous health benefits, various health products such as canned foods, fruit wine, fruit vinegar, beverages, teas, jams, and other foods have been developed worldwide. In summary, this review provides a comprehensive and up-to-date overview of the ethnopharmacology, phytochemistry, quality control, functions, and food application of R. chingii, contributing to the advancement of health food and medical development related to this plant.

Rapid isolation and precise quantification of target cancer cells are crucial for precision medicine applications. Conventional fluorescence-based methods require bulky optical instrumentation and specialized expertise. Recent advances in label-free microfluidic techniques have attempted to overcome these limitations but often suffer from reduced reliability and throughput when integrating multiple functions. Here, we demonstrate an electroactive microfluidic platform that integrates functions of selective concentration, particle focusing, and single-cell level quantification without introducing additional complex physical microstructures. Our device employs the dielectrophoresis (DEP) effect combined with an interdigitated cell sorter to achieve selective cell concentration. For quantification and characterization, the device leverages the impedimetric Coulter principle to achieve precise particle counting and characterization at single-cell resolution. To address the inherent tradeoff between sensitivity and throughput in the traditional Coulter counter, we utilize the tilted interdigitated electrode configuration excited by an amplitude-modulated (AM) Positive DEP (pDEP) signal instead of the commonly employed narrow channel or sheath flow to realize the effective focusing and alignment of the cell stream. The focusing module is combined with our side-counter design to detect cells. The performance of our device and its embedded modules has been verified with mixed breast cancer and blood model cell lines, where high consistency between optical and electrical detection has been demonstrated. We expect the integration of the proposed AM-pDEP focusing approach and the corresponding microfluidic design for cell sorter and on-chip flow cytometry would offer an alternative engineering solution to the stream-based on-chip single-cell analysis where reliable cell focusing and single-cell sensing are required.

The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants (e.g., hydrogen peroxide (H2O2) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnOx ((MnII)1(MnIII)2.1(MnIV)2.6O9.35), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen (1O2) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1O2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H2O2-mediated 1O2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnOx nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1O2 inducing, and stimulated H2O2 conversion into highly toxic 1O2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment.

Baccaurea ramiflora has an unstable ripening period. Herein, five typical periods of fruit ripening of ‘LR’ Baccaurea ramiflora were analyzed by non-targeted metabolomics techniques. The results showed that ripening started 73 days after flowering and reached the ripening criterion at 93 days, a total of 451 differential metabolites were identified for the five periods. KEGG enrichment pathway showed that significant changes in citric acid were significantly correlated with changes in the downstream substance spermine (R2 = 0.9068, y = −5.49 + 0.66×), while citric acid (R2 = 0.9982) and spermine (R2 = 0.9841) were negatively correlated with the sugar-acid ratio. Citric acid was the main component of titratable acid and spermine (R2 = 0.9991) was positively correlated with titratable acid. We speculated that citric acid is a key taste marker for fruit ripening in ‘LR’ B. ramiflora. The results of the study provide new metabolic evidence for flavor changes and scientific basis for their quality improvement and exploitation in B. ramiflora.

Study region: The Yangtze River basin. Study focus: Clean water scarcity is one of the major constraints for human sustainable development. Previous diagnosis of water scarcity has focus on fluctuations in the amount of water needed by humans, while ignoring the imbalance between water supply and demand that is exacerbated by changes in water quality under the context of climate change. This study proposes a diagnosis framework for clean water scarcity analysis under future climate projections by combining climate and socioeconomic projections, hydrological system, environmental requirement and human water withdrawal simulations, and water quality projections. This framework is demonstrated in analyzing the clean water scarcity for near (2031–2060) and far (2070–2099) futures. New hydrological insights for the region: The results show that by the end of this century, the clean water stress index will decrease substantially, and the number of people potentially threatened by clean water scarcity is expected to decrease from 294.8 million to 159.1 million. Clean water scarcity is expected to ease as freshwater resources increase in the future. Based on scenario simulations, the results further reveal that mitigation measures for clean water scarcity are mainly affected by natural factors in near and far futures. These findings support that the proposed framework can provide a new perspective for assessing and explaining the multifaceted influences of climate change on clean water scarcity.

Summary: Background: This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. Methods: We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Findings: Higher exposures to NOx (HR = 1.20, 95% CI 1.05–1.38), NO2 (HR = 1.19, 95% CI = 1.03–1.36), PM2.5 (HR = 1.19, 95% CI = 1.05–1.36) and combined air pollution score (HR = 1.26, 95% CI = 1.11–1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. Interpretation: We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Funding: Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546).

Probabilistic linguistic term sets (PLTSs) provide a flexible tool to express linguistic preferences, which allow decision-makers to label linguistic information with different probabilities. In this paper, a method based on a PLTS is proposed to address multi-criteria decision-making problems (MCDM). We develop the theory of PLTSs and put forward a novel best–worst method (BWM), termed PL-BWM, based on PLTS. Our method fully reflects the preference information of decision-makers and accurately provides the importance level of the criteria. The combined weight of the criteria is obtained by merging PL-BWM-based subjective weights and similarity minimization-based objective weights. Upon introducing a three-way decision system to improve the TODIM method, a novel three-way TODIM method is proposed and showcased on an optimal new energy vehicle selection problem. The effectiveness and accuracy of the proposed method are verified by sensitivity analysis and comparative analysis. Our approach paves the way for new developments in solving MCDM problems and for novel applications in otherwise difficult ranking problems.

Synthetic Aperture Radar (SAR) data, known for its high spatial resolution and all-weather observation capabilities, holds immense promise in soil moisture monitoring. The Water Cloud Model (WCM) is widely applied in soil moisture inversion using SAR data. However, the optical vegetation indices employed in traditional WCM cannot synchronize with SAR data, and the polarimetric scattering information contained in current SAR vegetation indices is incomplete, consequently compromising the accuracy of SAR-based soil moisture retrieval. Therefore, this study proposes a method for soil moisture retrieval over cropland using a novel dual-polarization SAR vegetation index. The method initially combines SAR data covariance elements with backscatter information to establish a polarization scattering contrast parameter (mcp). Then, based on mcp and incorporating the degree of polarization, a polarization scattering correlation contrast parameter (Rcp) is defined. Rcp integrates the distinctive features of scattering differences and polarization states. Building on Rcp, a novel dual-polarization SAR vegetation index (DRVIs) is introduced. Ultimately, DRVIs are utilized in the WCM to achieve surface soil moisture retrieval in cropland. This research conducts experiments in four crop cover areas of the Carman test site in Canada, namely soybean, wheat, canola, and corn. Under VV and VH polarizations, the overall correlation coefficients between measured in-situ data and SSM estimates reach 0.89 and 0.84, respectively. Compared to SSM estimates based on NDVI and LAI products, SSM estimates based on DRVIs exhibit a notable improvement in accuracy, with enhancements of approximately 7.2 % and 12.7 %, respectively. This novel DRVIs is poised to expand the utilization of SAR data in monitoring vegetation growth and soil moisture retrieval.

Monitoring sensors in complex engineering environments often record abnormal data, leading to significant positioning errors. To reduce the influence of abnormal arrival times, we introduce an innovative, outlier-robust localization method that integrates kernel density estimation (KDE) with damping linear correction to enhance the precision of microseismic/acoustic emission (MS/AE) source positioning. Our approach systematically addresses abnormal arrival times through a three-step process: initial location by 4-arrival combinations, elimination of outliers based on three-dimensional KDE, and refinement using a linear correction with an adaptive damping factor. We validate our method through lead-breaking experiments, demonstrating over a 23% improvement in positioning accuracy with a maximum error of 9.12 mm (relative error of 15.80%)—outperforming 4 existing methods. Simulations under various system errors, outlier scales, and ratios substantiate our method’s superior performance. Field blasting experiments also confirm the practical applicability, with an average positioning error of 11.71 m (relative error of 7.59%), compared to 23.56, 66.09, 16.95, and 28.52 m for other methods. This research is significant as it enhances the robustness of MS/AE source localization when confronted with data anomalies. It also provides a practical solution for real-world engineering and safety monitoring applications.

Study region: China Study focus: There is usually a teleconnection between large-scale climate indices and runoff. Among multiple large-scale climate indices, Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO) have received increased attention due to their long periodicities and low-frequency variability. However, the short observations limit the study of runoff response to AMO and PDO. Taking Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) as study periods and focusing on summer runoff in China, this study aims to investigate 1) the major time scales at which AMO/PDO affects runoff, and 2) the individual and coupled effects of AMO and PDO on runoff by using last millennium climate model simulations. New hydrological insights for the region: AMO and PDO have stronger correlations with summer runoff at interdecadal time scales than at interannual time scales during MCA and LIA. For individual effects during MCA, the positive AMO phase can cause positive summer runoff anomalies in eastern China, northern China, and southern Qinghai-Tibet Plateau, while PDO has the opposite effect. The results during LIA are similar to those during MCA. For coupled effects during MCA, when the AMO phase is positive, the influence of PDO on runoff is much smaller than AMO. During LIA, the synergistic effects on summer runoff are shown by the in-phase AMO and PDO in southern China and the southern Qinghai-Tibet Plateau.

Study region: Xiangjiang and Hanjiang River basins in the Yangtze River basin, a humid subtropical inland region of central-southern China. Study focus: The general precipitation predictive skills of the mainstay numerical models are still rather limited beyond 10 days, further deteriorating the performance of sub-monthly streamflow prediction. This study proposes a sub-monthly streamflow prediction framework for organically combining stochastic weather generator (SWG) and monthly precipitation prediction to generate ensemble sub-monthly precipitation for streamflow prediction. The SWG-based schemes are then compared with the common numerical hydrometeorology ensemble streamflow prediction over two river basins in China. New hydrological insights for the region: Results show that the numerical streamflow predictions exhibit a less accurate deterministic performance than the SWG-based framework with the climatology scheme over sub-monthly horizon, with leadtime-averaged mean absolute relative error dropping from 19.9 % to 8.3 %, and 21.8–11.1 % for Xiangjiang and Hanjiang river basins, respectively. In addition, the more restrictive parametric adjustment procedure with adjusted precipitation amounts can bring added values and further improve the accuracy of SWG-based daily streamflow prediction for sub-monthly leadtimes. In terms of the probabilistic prediction performance, the SWG-based methods yield approximately equivalent results with the numerical hydrometeorology streamflow prediction, with leadtime-averaged Continuous Ranked Probability Skill Score of the scheme with modified parameters of precipitation amounts being 0.51 and 0.56 for Xiangjiang and Hanjiang River basins, respectively. Furthermore, the SWG-based schemes are more suitable for predicting high-flow events during the flood season, with a significantly smaller Brier Score. However, there are little improvements in probabilistic prediction performance when transition probabilities of precipitation occurrence are progressively modified.

The interfacial adhesion plays a key role in the mechanical, electrical and corrosion properties of composites. For the high strength-conductive CuCrZr/CuZrAl metallic glass composites, the interface between the two phases suffered from excessive oxide film due to the strong affinity to oxygen of the Zr element. The rare earth particles Sc/Y are introduced into CuCrZr-30 wt% CuZrAl metallic glass composites to control the interface oxide layer and promote the properties of the composites. The incorporated Sc/Y particles trigger significant grain refinement effect in the CuCrZr matrix, which is enhanced with the increasing Sc/Y content. Sc particles offers a more pronounced grain refinement effect compared to the Y particles, yielding a more positive impact on the strength of the composites. With 1.5 wt% Sc added, the strength of the composites reaches up to 1180 MPa, while maintaining 24.8 % IACS. Moreover, the in-situ generation of rare earth oxides (Sc2O3/Y2O3) effectively enhances the interface bonding between the CuZrAl metallic glass and the CuCrZr matrix, improving the corrosion resistance of composites. This suggests a viable approach to construct dual-phase multiscale structure in the Cu-based composites with optimized interfaces and multiple strengthening effect.

As a typical alkaline hazardous waste, municipal solid waste incineration fly ash is used for CO2 storage and cement supplementary material, contributing to carbon emission reduction and hazardous waste management. This study proposed a new idea of using ultrasonic accelerated carbonated fly ash (UFA) to modify CO2 mineralization cured cement, aimed at recycling FA while enhancing cement performance. Incorporating small amounts of UFA (5% and 10%) significantly improved the mechanical properties of cement paste, with the optimal inclusion of 10% UFA yielding a compressive strength of 50.23 MPa—higher than that of pure cement (41.04 MPa). The UFA contributed to pore filling and acts as a nucleation site for CO2 mineralization, forming stable flaky calcite and thus enhancing the microstructure. Conversely, higher UFA contents (20% and 50%) reduced performance due to a dilution effect that impaired the hydration product structure. Kinetic analysis via the Avrami-Erofeev model revealed that CO2 diffusion and crystal growth primarily control the mineralization reaction. The 50%UFA cement paste exhibited the greatest carbon fixation depth, with a carbon sequestration capacity of 186 g-CO2/kg-PC. This was attributed to its enhanced porosity and pore size, which facilitated CO2 diffusion. The 10%UFA cement paste, which had the highest compressive strength, also achieved a carbon sequestration capacity of 158 g-CO2/kg-PC, surpassing the 144 g-CO2/kg-PC of the pure cement paste. Moreover, the proposed UFA-modified CO2 mineralization cement displayed a low risk of heavy metal leaching under alkaline or acidic environment.

Fish gut-liver health and gut microbial disorders have restricted the sustainable development of aquaculture. Rare earth elements are neglected potential trace elements in intensive farming. The aim of the study was to explore the effects of novel organic rare earths on growth performance, gut-liver health, and gut microbiota of golden pompano via supplementation of 0.2 g/kg novel organic rare earths in the diet. Firstly, the novel organic rare earths can effectively enhance the WG and SGR, and increase the CR of golden pompano, indicating that the novel organic rare earths could enhance growth performance. Meanwhile, dietary supplementation of novel organic rare earths alleviated liver inflammation by decreasing the expression of hepatic pro-inflammatory cytokines and elevating that of anti-inflammatory cytokines. In addition, the novel organic rare earths enhanced the tight junctions between intestinal epithelial cells to maintain the integrity of the intestinal barrier and reduced intestinal inflammation. Finally, the novel organic rare earths altered the composition (enrichment of beneficial bacteria), diversity and the ratio of ‘Functional Group 2/Functional Group 1’ of gut microbiota, which may contribute to the enhancement in growth of golden pompano. In conclusion, our study found that novel organic rare earths enhanced the growth performance of golden pompano and gut-liver health, altered the structure and function of the gut microbiota to alleviate microbiota imbalance. Thus, this study provides insights into the link between gut microbiota and host health and growth, and helps to promote the utilization of novel organic rare earths as dietary additive in fish culture.

Lithium-ion batteries (LIBs) are widely regarded as established energy storage devices owing to their high energy density, extended cycling life, and rapid charging capabilities. Nevertheless, the stark contrast between the frequent incidence of safety incidents in battery energy storage systems (BESS) and the substantial demand within the energy storage market has become increasingly prominent. Firstly, despite the escalating demand for energy density in BESS, in-depth understanding of thermal runaway (TR) in large-capacity LIBs and the associated risks posed by battery venting gases (BVG) remains elusive. Secondly, the absence of consensus regarding the selection of fire extinguishing agents and the development of fire suppression strategies for BESS has resulted in prevailing technological inadequacies in active suppression measures. This manuscript comprehensively reviews the characteristics and associated influencing factors of the four hazard stages of TR, TR propagation, BVG accumulation, and fire (BVG combustion and explosion), particularly focusing on the spatial characteristics of energy storage. Combining the above analysis, the suppression mechanisms, effects, and applicable hazard stages of extinguishing agents are analyzed, and the positive effects of fire suppression strategies are discussed. Additionally, the experimental research, mathematical calculation and numerical simulation methods pertaining to the combustion and explosion characteristics are summarized, alongside offering corresponding research suggestions and prospects aimed at fostering advancements in BESS safety.

Bacillus velezensis TCS001 is a novel biocontrol bacterium with broad-spectrum antifungal activity and plant growth-promoting effects, holding great potential for development in agricultural production. This study optimized the fermentation conditions for B. velezensis TCS001 through single-factor experiments combined with response surface methodology, and developed a formulation for TCS001 suspension concentrate (TCS001-SC). The efficacy of TCS001-SC to promote the growth of strawberries and to prevent and control strawberry anthracnose was evaluated. The optimal liquid fermentation condition for TCS001 was determined to be 2.89 % soluble peanut cake powder, 3.0 % glucose, 3.0 % soluble starch, 0.002 % FePO4, 0.006 % KCl, 0.6 % NaCl, 0.05 % MgCl2·6H2O, 0.3 % K2HPO4, 0.15 % KH2PO4, 0.05 % CaCO3, 0.005 % MnSO4, a working volume of 31 % (77.5 mL/250 mL), a rotation speed of 173 r/min, a cultivation temperature of 28°C, an inoculum volume of 1.0 %, and a pH of 7.0. The 15 L fermenter upscale culture achieved a spore count of 9.46 × 109 CFU/mL, which was 2.01 times the spore count of 4.7 × 109 CFU/mL before optimization, and a preliminary TCS001-SC was developed with the fermented broth as the main component. Agar plate confrontation tests showed that TCS001 had antifungal activity against five types of anthracnose fungi, with inhibition rates ranging from 70.3 % to 87.2 %. TCS001-SC could promote the growth of strawberries and induce a rapid defense enzyme response in their leaves, enhancing the plant's resistance to pathogens. After treatment, individual strawberry plants showed significant increases in the number of leaves, fresh weight of stems and leaves, root fresh weight, leaf area, plant height, and the content of POD, SOD, CAT enzymes, GA, IAA, and ABA compared to the control.Additionally, it shows good prevention and control effects against strawberry anthracnose, with a control efficacy of 60.45% after five spray treatments at a concentration of 2 × 107 CFU/mL, which is not significantly different from the efficacy of commercial microbial agents such as Bacillus subtilis wettable powder, subsequent field trials will be conducted to determine its potential as a microbial pesticide. This study provides important support for the future industrial production and application of the strain TCS001.

Optic nerve injury induces the loss of retinal ganglion cells and optic nerve atrophy. Our previous study demonstrated the neuroprotective effects of Citrus in the optic nerve crush (ONC) injury model. To explore the underlying neuroprotective mechanism, we focus on the changes in gene expression profile pre- and post-Citrus treatment in the ONC injury model. The results suggested that the Citrus regulated the chemokine signaling pathway and P53 signaling pathway, etc. Four genes were identified as potential target genes (Melk, Mki67, Ccnb1, and Cenpf). Subsequent qRT-PCR and western blot confirmed that Citrus regulated cell apoptosis and inflammation-related gene expression, and inhibited P53 activation-induced cell death. The present study demonstrated that the neuroprotective effect of Citrus was achieved through the regulation of the P53/BCL-2/BAX pathway and the expression regulation of four critical genes, which provide novel therapeutic targets for the therapy of optic nerve injury.

Current condition monitoring of three-phase inverters is mainly for DC-link capacitance, with little attention paid to AC-side parameters, and some of these methods require the addition of DC current sensors or changes in operating conditions. In fact, the AC side inductance degrades with use. In particular, the neutral inductors of three-phase four-wire inverters need to be condition-monitored because of the high failure rate due to the long term exposure to huge ripples. To address the above problems, this paper proposes a zero-sequence current injection method, which can take into account both the AC and DC sides, satisfy the parameter identification of “large capacitance and small inductance”, and does not need to add additional sensors or sampling circuits. Then, the zero-sequence components are extracted by a high-order band-pass filter and a recursive least squares filter. Next, the extracted components are processed by the proposed adaptive forgetting factor recursive least square observer to obtain the recognized parameter values. The speed and accuracy of parameter identification are greatly accelerated by the adaptive processing of the forgetting factor. The three-phase simultaneous identification and back-propagation iteration for the neutral inductor improves the identification accuracy and speed. Finally, a three-phase four-wire experimental platform is built. The experimental results show that the proposed method is still effective under different types of loads and load fluctuation.© 2017 Elsevier Inc. All rights reserved.

Bursaphelenchus xylophilus is a pathogenic nematode responsible for pine wilt disease, which can cause the demise of pine trees and discoloration of trunks. As rotenone is an important botanical pesticide, its impact on B. xylophilus was investigated through RNA-seq to understand the response mechanism of nematode. The bioassay results yielded the 12-h LC30 (1.35 mg L−1) and LC50 (2.60 mg L−1) values for rotenone. Differential gene expression analysis identified 172 and 614 differentially expressed genes (DEGs) in B. xylophilus exposed to two different concentrations of rotenone (1.35 and 2.60 mg L−1). To validate these findings, the expression patterns of 10 DEGs were confirmed through RT-qPCR. Additionally, all DEGs were categorized into eight gene expression profiles using STEM. Notably, the gene ontology (GO) processes of ''single-organism process,'' ''metabolic process,'' and ''catalytic activity'' were prominently enriched in rotenone-treated samples, suggesting a role for metabolic and catalytic pathways in the nematode's response to rotenone stress. KEGG pathways related to ''carbon metabolism,'' ''drug metabolism-cytochrome P450,'' and ''metabolism of xenobiotics by cytochrome P450'' were similarly enriched, indicating potential mechanisms for detoxification resistance and oxidative stress resistance. The analysis pointed to the pivotal roles of detoxification- and oxidoreduction-related genes, as well as signal transduction-related genes, in enabling B. xylophilus to adapt to rotenone exposure. These insights could markedly enhance our understanding of nematode resistance mechanisms and potentially inform the development of more effective rotenone-based strategies for controlling B. xylophilus.

NLRP3 inflammasome activation in macrophages is involved in paraquat-induced acute lung injury (ALI). MANF exerts an inhibitory effect against inflammation and cell death. The aim of this study was to investigate the role of MANF in paraquat-stimulated alveolar macrophages and the potential mechanism. Paraquat-induced ALI mouse model was established by intraperitoneally injection of 30 mg/kg of paraquat. The lung pathological changes were observed by hematoxylin and eosin staining. The expression of MANF/DDX3X/NLRP3/Caspase-1 in mice lung macrophages was evaluated by double immunofluorescence staining and western blot. NLRP3 inflammasome activation and pro-inflammatory cytokines (IL-1β and IL-18) in paraquat-stimulated macrophage transfected with MANF overexpression plasmid (pcDNA3.1-MANF) or siRNA-MANF were measured by Western blot. The protein–protein interaction of MANF/DDX3X/NLRP3 was verified by Co-immunoprecipitation. As a result, MANF/DDX3X/NLRP3/Caspase-1 were upregulated in alveolar macrophages of paraquat-induced ALI in mice. In paraquat-stimulated alveolar macrophages, upregulation of MANF and DDX3X were also observed, accompanied by NLRP3 inflammasome activation. In addition, overexpression of MANF inhibited NLRP3 inflammasome activation in paraquat-stimulated alveolar macrophages. In contrast, knockdown of MANF aggravated NLRP3 inflammasome activation. Co-immunoprecipitation results revealed that DDX3X could bind to MANF and NLRP3, but MANF could not bind to NLRP3 in paraquat-stimulated alveolar macrophages. Furthermore, Co-immunoprecipitation of truncated three fragments of DDX3X confirmed MANF can interact with the helicase core of DDX3X which is the binding site for NLRP3. Taken together, MANF exerted a protective effect against paraquat-induced cytotoxicity by inhibiting the NLRP3 inflammasome activation in macrophages via competitive binding to the helicase core of DDX3X.

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.

The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60℃, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2–) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2– were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09–0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %–22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.

This study evaluates the application of supercritical carbon dioxide chelation extraction technology for treating heavy metal ions (Zn2+ and Cr3+) in drilling fluid waste. Through a combination of experimental and molecular dynamics simulation methods, the influence of extraction parameters (temperature, pressure, duration, and chelating agents) on the extraction efficiency are investigated. Findings show that increased duration and pressure significantly improve extraction efficiency, while temperature has a complex effect, initially increasing efficiency but plateauing and slightly decreasing at higher temperatures. The optimum extraction condition with pressure of 220 bar, temperature 348.15 K and an extraction duration of 70 min using ethylene diamine tetraacetic acid (EDTA) as the chelating agent has been determined. Importantly, molecular simulation analysis revealed that citric acid outperforms EDTA in terms of Zn2+ and Cr3+ aggregation by forming larger aggregates with greater numbers of molecules while reducing overall aggregate count. Furthermore, optimization of extraction pressure in the EDTA system shows potential benefits. These results suggest that supercritical carbon dioxide chelation extraction technology has strong potential for environmentally friendly and reliable waste management in the drilling industry. This study represents a significant step forward in developing sustainable solutions for heavy metal removal from drilling fluid waste.

Grass carp hemorrhagic disease is caused by the grass carp reovirus (GCRV). The disease spreads rapidly and has a high fatality rate, which seriously affects grass carp culture. Moreover, the molecular mechanisms underlying grass carp hemorrhagic disease remain unclear. To decipher the effects of GCRV on grass carp tissues, resistant grass carp A (GA) and susceptible grass carp B (GB) were selected through GCRV treatment, and control grass carp C (GC) was also established. The gill, liver, and muscle tissues exhibited different onset symptoms under the influence of GCRV by histological observation. We selected muscle samples with significant differences in symptoms for Illumina RNA sequencing. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed 3512, 3074, and 1853 differentially expressed genes between ''GC vs. GB,'' ''GC vs. GA,'' and ''GA vs. GB,'' respectively. Additionally, 40 differential immune-related genes and 28 differential interferon-stimulating genes (ISGs) related to the interferon (IFN) pathway were identified. The expression of immunogene-related genes of GB and GA, such as MDA5, IL-34, NF-KB, TRIM25, SOCS3, CEBPB, and BCL2, and genes associated with the JAK-STAT signaling pathway, such as IRF4, STAT1, STAT3, JAK 1, and JAK 2, was significantly upregulated. The IFN and JAK-STAT signaling pathways were closely related to anti-GCRV infection. The transcriptome data and predicted immune genes and ISGs in this study provide novel insights into the treatment of GCRV.

Background: The gut microbiota thrives in a complex ecological environment and its dynamic balance is closely related to host health. Recent studies have shown that the occurrence of various diseases including prostate inflammation is related to the dysregulation of the gut microbiome. Objective: This review focus on the mechanisms by which the gut microbiota induces prostate inflammation and benign prostatic hyperplasia and its therapeutic implications. Materials and methods: Publications related to gut microbiota, prostate inflammation, and benign prostatic hyperplasia (BPH) until April 2023 were systematically reviewed. The research questions were formulated using the Problem, Intervention, Comparison/Control, and Outcome (PICO) frameworks. Results: Fifteen articles covering the relationship between the gut microbiota and prostate inflammation/BPH, the mechanisms by which the gut microbiota influences prostate inflammation and BPH, and potential therapeutic approaches targeting the gut microbiota for these conditions were included. Conclusion: Short-chain fatty acids (SCFAs), which are metabolites of the intestinal microbiota, protect the integrity of the intestinal barrier, regulate immunity, and inhibit inflammation. However, dysregulation of the gut microbiota significantly reduces the SCFA content in feces and impairs the integrity of the gut barrier, leading to the translocation of bacteria and bacterial components such as lipopolysaccharide, mediating the development of prostate inflammation through microbe-associated molecular patterns (MAMPs).

Essential oils with β-caryophyllene, citral, and linalool as key compounds often exhibit some anti-anxiety like effects in aromatherapy. However, evidence of the effect of these three compounds through human inhalation remains limited. It is worth exploring their potential anxiolytic effect through the olfactory pathway, and finding out whether the three compounds lead to different physiological responses. A total of 48 subjects were randomly assigned to three odor (β-caryophyllene, citral, and linalool) inhalation groups and one control (odorless jojoba oil) group. Stress stimulation was induced using n-back and mental arithmetic tasks. The odor was administered before the task test session. Assessments including the State-Trait Anxiety Inventory (STAI), electroencephalogram (EEG) activities, facial expressions, several physiological indicators, and a self-report scale of subjective perception of the odor environments were carried out. The changes before and after inhalation, as well as the inter-group differences, were analyzed. Both β-caryophyllene and citral inhalation led to a significant decrease in anxiety levels, while only β-caryophyllene resulted in a notable reduction across both sub-scales of STAI. Following the odor inhalation, heart rate significantly decreased in all three groups, with the β-caryophyllene group exhibiting the most pronounced decline. While the systolic blood pressure of the linalool group demonstrated a statistically significant difference. Regarding facial expressions, β-caryophyllene significantly increased the ratio of 'Happiness' and decreased the ratio of ‘Fear'. In the non-task state, citral reduced the power of frontal alpha, delta, and theta waves while β-caryophyllene had a similar effect. All odor inhalation groups showed increased delta and theta waves after the task compared with the control group, with the β-caryophyllene group having notably lower frontal beta waves. β-Caryophyllene and citral exhibited good anti-anxiety effects. Subjects receiving different odors showed different EEG and physiological responses, indicating the differences in emotional regulation ways among the three compounds.

Air blast fireball of the composite explosive is an important way to destroy the target and effectively determines the damage effect. Herein, based on the effect of aluminum powder content on the explosion reaction kinetics of HMX-based aluminized explosives, the cylindrical charges with positive gradient structure (PGS) and negative gradient structure (NGS) were designed and prepared to control the structure and size of air blast fireball. The PGS cylinders exhibited lateral shuttle-shaped flame/fireball and the width of the fireball was 3.901 m, which was increased by about 14% compared with homogeneous cylinders. The NGS cylinders led to the vertical shuttle-shaped flame/fireball that the height of the air blast fireball reached 4.049 m, and had longer durations of the fireball. The numerical fitting results show that the lateral shuttle-shaped flame/fireball and vertical shuttle-shaped flame/fireball gradually changed into spherical-like flame/fireball with an increase from 0 to 30 wt% of outer and inner layer HMX content, respectively. The vertical shuttle flame/fireball gradually changed into a spherical-like flame/fireball with the increase of HMX content. This is a feasible way to regulate the shape and size of the air blast fireball through gradient adjusting the distribution of HMX and Al, which could provide an effective strategy to improve the damage effect.

Both ambient fine particulate matter (PM2.5) and aging are important urban concerns. However, the associations between PM2.5 constituents and the acceleration of aging (AA) remain unclear. We included 16,051 adults (aged 25–80 years) with 19,252 medical observations in Taiwan during 2008−2017. 2-year average PM2.5 and its five major constituents were assessed using a two-stage machine learning model at a resolution of 1 km2. AA was determined by the difference between the Klemera–Doubal biological age and chronological age. A linear mixed model (LMM) with inverse probability weights was used to examine the associations between AA and air pollution. In a semi-randomized study design, we applied a post-matching LMM to assess the impacts of changes in air pollution exposure on AA. Each interquartile range increase in ambient PM2.5, SO4-2, NO3–, NH4+, organic matters (OM), and black carbon (BC) was associated with a 0.20 (95 %confidence interval [CI]: 0.17–0.24), 0.19 (0.15–0.23), 0.14 (0.11–0.18), 0.21 (0.17–0.24), 0.22 (0.19–0.26) and 0.25 (0.21–0.28) year increase in AA, respectively. BC was generally associated with the greatest increase in AA as compared to other constituents. We did not find evident thresholds in their concentration–response associations. Participants exposed to increased levels of PM2.5, SO4-2, NO3–, NH4+, OM, and BC experienced an increase in AA of 0.11 (−0.07–0.29), 0.20 (0.02–0.39), 0.15 (−0.02–0.33), 0.12 (−0.07–0.31), 0.24 (0.07–0.41), and 0.30 (0.07–0.52) years, respectively, compared to those exposed to decreased/unchanged levels. Long-term exposure to ambient PM2.5 and its constituents may accelerate biological aging among Chinese adults. Exposed to increased levels may further aggregate the aging process. This study suggests that reducing exposure to air pollution is beneficial, even for residents within moderately-to-highly polluted regions, such as Taiwan. Rigorous regulation of PM2.5 and its constituents may prevent the acceleration of biological age.