Search

Abstract The interaction between lattice vibrations and electrons plays a key role in various aspects of condensed matter physics — including electron hydrodynamics, strange metal behavior, and high-temperature superconductivity. In this study, we present systematic investigations using Raman scattering and angle-resolved photoemission spectroscopy (ARPES) to examine the phononic and electronic subsystems of the topological superconductor candidate 2M-WS2. Raman scattering exhibits an anomalous nonmonotonic temperature dependence of phonon linewidths, indicative of strong phonon–electron scattering over phonon–phonon scattering. The ARPES results demonstrate pronounced dispersion anomalies (kinks) at multiple binding energies within both bulk and topological surface states, indicating a robust and mode-selective coupling between the electronic states and various phonon modes. These experimental findings align with previous calculations of the Eliashberg function, providing a deeper understanding of the highest superconducting transition temperature observed in 2M-WS2 (8.8 K) among all transition metal dichalcogenides as induced by electron–phonon coupling. Furthermore, our results may offer valuable insights into other properties of 2M-WS2 and guide the search for high-temperature topological superconductors.

Abstract Background Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. Methods We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. Results Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. Conclusions Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

W–Cu composite powders prepared via the wet chemical method in the form of W-coated Cu contributed greatly to the materials' density and the homogeneity. The powders were modified to prepare large quantities of W–Cu composites with excellent properties via metal injection molding (MIM). In this study, the precursors’ reaction process, the formation mechanism of W-coated Cu, and MIM process were systematically investigated. Results showed that W–Cu composite powders in this coating form could ensure the homogeneity of W and Cu and reduce Cu loss during sintering. In addition, W–Cu composites that fulfill the performance specifications for electronic packaging have been effectively synthesized through MIM employing the novel polyoxymethylene (POM)-based binders. Regarding thermal properties, the W–15Cu composites exhibit an impressive thermal conductivity of 212 W/(m·K) and a minimal coefficient of thermal expansion at 7.01 ppm/°C. These characteristics outperform those of other materials documented in related literature. This study provided a useful referential value to the combination of W–Cu composites in scientific research and engineering applications.

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Recent studies have demonstrated that bitter taste receptors are distributed not only in oral cavity but also in non-gustatory systems, such as the respiratory, digestive, reproductive and cardiovascular systems. The physiological role of bitter taste receptors is to recognize bitter substances or bacterial secretions, to trigger the immune response and to maintain the internal environmental homeostasis. In addition, oral bitter taste receptors are expressed not only in taste buds, perceiving bitter taste, but also in many other parts of periodontal tissues, which is the potential treatment target for oral infectious diseases. This review summarized the expression and distribution of oral bitter taste receptors which was off the taste buds and their roles in regulating oral inflammation and oral bacteria, discussed the effects of genetic polymorphism of bitter taste receptor 38 subtype(TAS2R38)on innate immunity and its relationship with the susceptibility of dental caries and periodontal, aimed to provide novel ideas for the better prevention and treatment of dental caries and periodontal diseases.

Abstract Background CAR-T cell therapy represents a novel approach for the treatment of hematologic malignancies and solid tumors. However, its implementation is accompanied by the emergence of potentially life-threatening adverse events known as cytokine release syndrome (CRS). Given the escalating number of patients undergoing CAR-T therapy, there is an urgent need to develop predictive models for severe CRS occurrence to prevent it in advance. Currently, all existing models are based on decision trees whose accuracy is far from meeting our expectations, and there is a lack of deep learning models to predict the occurrence of severe CRS more accurately. Results We propose PrCRS, a deep learning prediction model based on U-net and Transformer. Given the limited data available for CAR-T patients, we employ transfer learning using data from COVID-19 patients. The comprehensive evaluation demonstrates the superiority of the PrCRS model over other state-of-the-art methods for predicting CRS occurrence. We propose six models to forecast the probability of severe CRS for patients with one, two, and three days in advance. Additionally, we present a strategy to convert the model's output into actual probabilities of severe CRS and provide corresponding predictions. Conclusions Based on our findings, PrCRS effectively predicts both the likelihood and timing of severe CRS in patients, thereby facilitating expedited and precise patient assessment, thus making a significant contribution to medical research. There is little research on applying deep learning algorithms to predict CRS, and our study fills this gap. This makes our research more novel and significant. Our code is publicly available at https://github.com/wzy38828201/PrCRS . The website of our prediction platform is: http://prediction.unicar-therapy.com/index-en.html .

This study focuses on conducting friction-stir processing (FSP) on 3 mm thick LA141 alloy using different tools. Under low heat input conditions of 600 rpm and 200 mm/min, the use of the WC-Co cemented carbide tool successfully produced a defect-free stir zone. This stir zone exhibited an ultrafine grain structure resulting from continuous dynamic recrystallization. Additionally, the stir zone introduced massive grain boundaries, nanoscale MgAlLi2 particles, and stacking faults. The stir zone displayed a favorable balance of strength and ductility. The enhanced strength is attributed to the inhibitory effect of nanoscale MgAlLi2 particles, grain boundaries, and Lomer-Cottrell locks on dislocation movement. The improved work hardening ability and ductility can be attributed to the increase in stacking faults, Lomer-Cottrell locks, and deformation twins during deformation. Furthermore, the stir zone showed improved corrosion resistance, characterized by lower corrosion current density and larger polarization resistance. This improvement in corrosion resistance can be attributed to multiple factors. These include the reduced defect density, refined and evenly distributed MgLiAl2 particles that weakened galvanic corrosion effects, and the presence of more stable Li2CO3 and Al2O3 compounds that resulted in a compact and protective film.

Objective: Conducting research on fast, accurate, and non-destructive prediction methods for the shelf life of prepackaged instant beef had great significance for ensuring the safety of the shelf life of product. Methods: Using prepackaged instant beef as the analysis object, the T2 relaxation time of low field nuclear magnetic resonance (NMR) proton was collected from the sample, and a quantitative analysis model for the moisture content of instant beef was established. A prediction model for the shelf life of prepackaged instant beef was established based on the sensory acceptance of the sample. Results: The lateral relaxation time of the low-field nuclear magnetic resonance spectrum of prepackaged instant beef could better reflect the quality changes of spaceflight instant beef with the extension of storage time. A water content prediction model for instant beef was established, with a prediction error of less than 4%. The correlation coefficient (r) of the modeling set was 0.9405, the corrected standard deviation (RMSECV) was 34.5, and the relative analysis error (RPD) was 3.1. Ten samples stored for a certain period of time but not involved in modeling were predicted to be close to the end of shelf life. The correlation between the predicted results and the measured values was 0.99, and the error range of the predicted results was 0.7% to 9.9%. The RMSEP was 13.6. The accuracy of the prediction model met the accuracy requirements of shelf life prediction. Conclusion: Low field nuclear magnetic resonance technology would have potential application in predicting the shelf life of prepackaged instant beef products.

ABSTRACT: Two trials were conducted to draw the phase-response curve of productive and immunological variables in heat-exposed layer chickens at different ages (71 to 130 d, and 211 to 270 d). Birds were acclimated to the following conditions for 60 d: constant optimal ambient temperature at 24°C and high ambient temperature at 34°C for 8 h/d (10:00–18:00). Data collection and biochemical measurements were performed every 10 d. In both age ranges, high temperature favored the innate immunity (P < 0.01) at the cost of performance (P < 0.05) during a given period, including the relative abundance of B and T-helper lymphocytes, lymphocyte proliferation ratio (B and T lymphocytes), and serum immunoglobulin contents (IgG and IgM) in the peripheral blood, as well as splenic expression of inflammation-related genes (iNOS, TLR-4, TNF-α, IL-6, and INF-γ). Compared with laying hens, growing pullets showed a time-delayed activation of immune response following heat challenge, and had no immunosuppression up to the end of exposure. Overall, the immune system of layer birds has a trade-off with production tissues in a hot environment, and exhibits distinct age-range-specific responses of acclimatization.

Previous researches reported that burdock (Arctium lappa L.) root had lipid-lowering effects. The potential mechanisms needed to be further clarified. In this study, the effects and mechanisms of polyphenols (ALP) and polysaccharides (ALS) of burdock on hyperlipidemia rats were explored. The results revealed that ALP and ALS significantly inhibited the development of hyperlipidemia and reduced lipid levels in serum and liver. Meanwhile, ALP significantly decreased the activity of intestinal esterase enzyme. ALP and ALS significantly improved the imbalance of the microbiota by increasing the diversity of the intestinal microbiota and the abundance of the microbiota that produced short-chain fatty acids, and thus increased the content of acetic acid in short-chain fatty acids in the feces of hyperlipidemic rats. These results revealed that burdock played a lipid lowering effects by regulating intestinal dysbiosis due to hyperlipidemia, and ALP and ALS were the bioactive components of these effects.

IntroductionTo evaluate the preoperative health-related quality of life (HRQoL) and influencing factors of HRQoL in patients undergoing thyroidectomy based on patient-reported outcomes.Materials and methodsPatients who were diagnosed and treated in Sichuan Cancer Hospital from February 2022 to December 2022 and were scheduled to undergo thyroidectomy were included. Each participant completed the basic information questionnaire and patient-reported outcome assessment scales before surgery. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30), the Thyroid Cancer-Specific Quality of Life (THYCA-QoL), and the Hamilton Anxiety Scale (HAMA). The Wilcoxon rank sum test or the Kruskal-Wallis test was used to analyze the association between patient characteristics and HRQoL, and the variables with statistical significance were included in multiple linear regression analysis.Results450 patients were included in the study. According to the analysis of the THYCA-QoL scores, the psychological subscale was the most complained about. Anxiety was the most common symptom of the HAMA. Factors associated with worse general QoL on the EORTC QLQ-C30 included nondiagnostic/unsatisfactory fine-needle aspiration (FNA) result. Planned lateral neck dissection and nondiagnostic/unsatisfactory FNA result were influential factors for preoperative anxiety. Males and longer sleep duration were associated with better thyroid cancer-specific QoL, better general QoL, and less anxiety.ConclusionThe preoperative HRQoL of patients undergoing thyroidectomy was generally good. Females, insufficient sleep duration, planned lateral neck dissection, and nondiagnostic/unsatisfactory FNA result were associated with worse preoperative HRQoL.

The relationship between bacteria and tumors has been the hot spot of clinical research in recent years. Pseudoglutamicibacter cumminsii is an aerobic Gram-positive bacterium commonly found in soil. Recent studies have identified P. cumminsii in patients with cutaneous and urinary tract infections. However, little is known on its pathogenesis as well as involvement in other clinical symptoms. In this study, we first report the isolation of P. cumminsii in blood of an epithelial mesothelioma patient. The clinical and laboratory characteristics of P. cumminsii were first described and evaluated. The pure colony of P. cumminsii was then identified using automated microorganism identification system and mass spectrum. The whole genome of the newly identified strain was sequenced with third generation sequencing (TGS). The assembled genome was further annotated and analyzed. Whole genomic and comparative genomic analysis revealed that the isolated P. cumminsii strain in this study had a genome size of 2,179,930 bp and had considerable unique genes compared with strains reported in previous findings. Further phylogenetic analysis showed that this strain had divergent phylogenetic relationship with other P. cumminsii strains. Based on these results, the newly found P. cumminsii strain was named P. cumminsii XJ001 (PC1). Virulence analysis identified a total of 71 pathogenic genes with potential roles in adherence, immune modulation, nutrition/metabolism, and regulation in PC1. Functional analysis demonstrated that the annotated genes in PC1 were mainly clustered into amino acid metabolism (168 genes), carbohydrate metabolism (107 genes), cofactor and vitamin metabolisms (98 genes), and energy metabolism (68 genes). Specifically, six genes including yodJ, idh, katA, pyk, sodA, and glsA were identified within cancer pathways, and their corresponding homologous genes have been documented with precise roles in human cancer. Collectively, the above results first identified P. cumminsii in the blood of tumor patients and further provide whole genomic landscape of the newly identified PC1 strain, shedding light on future studies of bacteria in tumorigenesis.

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

Abstract Urbanization alters the thermal and dynamic environment of the local climate system, resulting in significant impacts on precipitation in both urban and adjacent areas. Nevertheless, there remains a significant gap in our understanding of urbanization‐induced effects on asymmetrical, symmetrical, and other precipitation patterns in urban agglomerations (UAs) with divergent background climates and geographic regions at different timescales. Specifically, this asymmetrical change pattern is characterized by an increase in heavy (or light) rainfall and a decrease in light (or heavy) rainfall. Here, we assessed the effects of urbanization on precipitation patterns across 18 UAs situated in diverse background climates and geographical areas in China at different timescales. The results demonstrate that urbanization predominantly alters precipitation patterns in UAs located in the humid region. Specifically, urbanization amplified asymmetrical changes in Yangtze River Delta, Pearl River Delta, Beibu Gulf, Middle Yangtze River, and Guanzhong, but exacerbated symmetrical changes in precipitation in some regions such as Chengdu‐Chongqing. Notably, the urbanization effect demonstrates greater significance at the hourly scale, as exemplified in the Yangtze River Delta, Pearl River Delta, and Middle Yangtze River, where the urban impact is nearly twice as pronounced when compared to the daily scale. Moreover, urbanization had either no effect or has a negative impact on precipitation patterns in UAs located within continental and arid regions. This is related to the intensity of urbanization, background climate and complex topography. This finding implies that urban managers should consider the impact of urbanization on precipitation patterns in different contexts to provide scientific guidance for urban planning.

Multiple myeloma (MM) is a Ubiquitin Proteasome System (UPS)-dysfunction disease. We previously reported that high PRAME transcript levels associated with unfavorable progression free survival (PFS) in patients with no bortezomib therapy, and bortezomib-containing regimen significantly improved PFS in patients with high PRAME transcript levels, which indicated that PRAME expression was prognostic for MM patients, and was related to proteasome inhibitor treatment. However, molecular mechanisms underlying the above clinical performance remain unclear. In the present study, MM cell models with PRAME knockdown and overexpression were established, and PRAME was identified to play the role of promoting proliferation in MM cells. P-Akt signaling was found to be activated as PRAME overexpressed. As a substrate recognizing subunit (SRS) of the E3 ubiquitin ligase, PRAME targets substrate proteins and mediates their degradation. CTMP and p21 were found to be the novel targets of PRAME in the Cul2-dependent substrate recognition process. PRAME interacted with and mediated ubiquitination and degradation of CTMP and p21, which led to accumulation of p-Akt and CCND3 proteins, and thus promoted cell proliferation and increased bortezomib sensitivity in MM cells.

Abstract Background This study aimed to assess the knowledge, attitudes and practices among medical workers toward outpatient diabetes information platform. Methods This web-based cross-sectional study was conducted between May 2023 and June 2023 at the First Hospital of Zhangjiakou, China. A self-designed questionnaire was developed to collect demographic information of medical workers, and assess their knowledge, attitudes and practices toward outpatient diabetes information platform. Results A total of 685 questionnaires were collected. Among the participants, 603 (88.03%) were female, 432 (63.07%) work in a tertiary hospital, 548 (80.00%) have a bachelor degree, 270 (39.42%) of them work in the department of internal medicine and 315 (45.99%) of them received previous training on outpatient diabetes information platform. The mean knowledge, attitudes and practices scores were 4.32 ± 1.27 (possible range: 0–6), 56.76 ± 5.72 (possible range: 14–70), and 32.22 ± 8.42 (possible range: 9–45), respectively. 350 (51.09%) of them have sufficient knowledge, 168 (24.53%) have positive attitudes and 395 (57.66%) have active practices. Pearson correlation analysis showed that knowledge was positively correlated with attitudes (r = 0.397, P

Abstract This study aimed to develop and validate a deep learning radiomics nomogram (DLRN) for the preoperative evaluation of axillary lymph node (ALN) metastasis status in patients with a newly diagnosed unifocal breast cancer. A total of 883 eligible patients with breast cancer who underwent preoperative breast and axillary ultrasound were retrospectively enrolled between April 1, 2016, and June 30, 2022. The training cohort comprised 621 patients from Hospital I; the external validation cohorts comprised 112, 87, and 63 patients from Hospitals II, III, and IV, respectively. A DLR signature was created based on the deep learning and handcrafted features, and the DLRN was then developed based on the signature and four independent clinical parameters. The DLRN exhibited good performance, yielding areas under the receiver operating characteristic curve (AUC) of 0.914, 0.929, and 0.952 in the three external validation cohorts, respectively. Decision curve and calibration curve analyses demonstrated the favorable clinical value and calibration of the nomogram. In addition, the DLRN outperformed five experienced radiologists in all cohorts. This has the potential to guide appropriate management of the axilla in patients with breast cancer, including avoiding overtreatment.

Abstract Background The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration. Methods The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1). Results Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly. Conclusion Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function. Graphical Abstract Tet2 interacts with Stat1 in the cytoplasm and suppresses IFN-γ-induced macrophage activation. Tet2 inhibitor decreases the combination of Stat1 and Tet2, activating the macrophages through the Jak-Stat pathway. The activation of macrophages increases the transcription and translation of the IL-6 and promotes liver regeneration. Video Abstract

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes disability worldwide. Exosomes released by fibroblast-like synoviocytes in RA (RA-FLSs-Exos) play a role in the development of RA, and circular RNAs (circRNAs) are important for RA progression. This study aimed to investigate the molecular mechanisms underlying the effects of RA-FLSs-Exos in RA and identify the potential pathway responsible for these effects. Methods We initially conducted microarray analysis to identify dysregulated circRNAs in exosomes associated with RA. We then co-cultured isolated RA-FLSs-Exos with chondrocytes to examine their role in RA. In vivo experiments were performed using collagen-induced arthritis mouse models, and circFTO knockdown was achieved through intra-articular injection of AAV5 vectors. Results Our findings revealed increased expression of circFTO in both RA-FLSs-Exos and synovial tissues from patients with RA. Exosomal circFTO hindered chondrocyte proliferation, migration, and anabolism while promoting apoptosis and catabolism. Mechanistically, we discovered that circFTO facilitates the formation of methyltransferases complex to suppress SRY-related high-mobility group box 9 (SOX9) expression with assistance from YTH domain family 2 (YTHDF2) through an m6A-dependent mechanism. Furthermore, inhibition of circFTO improved symptoms of RA in vivo. Conclusion Taken together, our study demonstrates that exosomal circFTO derived from FLSs contributes to the progression of RA by targeting SOX9. These findings highlight a promising target for treating RA.

In order to demonstrate the inhibitory effect of polyphenols from Arctium lappa roots (ALP) on lipase, the ALP were extracted and enriched. The content of total polyphenol was determined by Folin-Ciocalteu method, and the index components in ALP were determined by high performance liquid chromatography-UV (HPLC-UV) method. The inhibitory effect and type on lipase of ALP and its index components were determined by p-nitrophenyl butyrate (p-NPB) method. Combined inhibitory effect of them were evaluated by equivalent line diagram method and drug combination index (CI). The results showed that the total polyphenol of ALP reached 51.23%, and the contents of the five index components, i.e., neochlorogenic acid, cryptochlorogenic acid, caffeic acid, chlorogenic acid, and isochlorogenic acid A accounted for 12.87%. ALP showed reversible competitive inhibition on lipase with half maximal inhibitory concentration (IC50) value 1.706 mg/mL. The IC50 of neochlorogenic acid, cryptochlorogenic acid, caffeic acid, chlorogenic acid, and isochlorogenic acid A were 0.872, 0.910, 0.280, 0.847, 0.244 mg/mL, respectively. When the concentration ratio of chlorogenic acid and isochlorogenic acid A was 1:2.15, the CI value was 0.549, and when the concentration ratio of caffeic acid to isochlorogenic acid A was 1:0.87, the CI value was 0.282, which indicated synergistic inhibition effect on lipase. This study provides a theoretical basis for exploring the chemical basis of the lipid-lowering effect of Arctium lappa roots and its lipid-lowering mechanism, and layed a foundation for the development of Arctium lappa roots.

Fluctuations in the surface water are indicators of climatic and biological environmental variations. The water index method is the predominant approach for water extraction owing to its simplicity of operation and high efficiency. Recognizing the limitations of individual water indices in extracting water over dense time-sequences, this study introduces a combined water index (CWI) frequency method to improve the water extraction results. The research findings indicate the following: 1) CWI demonstrates superior extraction accuracy for various types of water when compared with other water indices, underscoring its higher precision and broader applicability. 2) By integrating CWI with the water frequency method, we propose an effective approach for dynamically monitoring water. This method accurately reflects changes in water under different conditions within dense time-sequence images. 3) Our results highlight the method's ability to precisely monitor dynamic water changes, efficiently extract various water types from Sentinel-2 data, and its potential for large-scale surface water mapping applications.

Satellite technology is an efficient tool, which can provide valuable observations for coastal areas from space. Compared with conventional bathymetric surveying approaches, remote sensing-based shallow water bathymetry retrieval methods have been widely used in recent years. Various empirical models have been proposed for deriving bathymetry of coastal shallow water, and prior topographic information is required to construct models. Traditional studies tend to select a cloud-free remote sensing image to map the coastal shallow water topography. As a result, in addition to the selection of empirical models, the high-quality remote sensing image and accurate prior topographic data are also of importance. This study aims to propose a method for mapping coastal shallow water bathymetry from multitemporal remote sensing imagery. Here, Sentinel-2 imagery time series are composited to produce a clear image, which can effectively avoid the contamination of clouds, water turbidity and other noises. ICESat-2 lidar altimeter data that contain accurate underwater elevations are used to provide topographic information. Moreover, Sentinel-2-based multispectral information and ICESat-2-based topographic information are combined for the coastal bathymetry retrieval by five empirical models (i.e., linear band model, ratio band model, support vector machine, neural network, and random forest). This proposed method is tested in Dongsha Atoll in South China Sea, and achieve a good performance [training: root mean square error (RMSE): 0.97 m ± 0.76 m, mean absolute percentage error (MAPE): 4.07% ± 0.046%, R-square (R2): 0.90 ± 0.14; validation: RMSE: 1.22 m ± 0.43 m, MAPE: 5.43% ± 0.035%, R2: 0.86 ± 0.089]. The comparison confirms that machine learning methods perform better than traditional methods, and the deep learning techniques can be further introduced in estimating shallow water bathymetry in the future, which is expected to achieve an excellent accuracy in bathymetry inversion.

Accurate information on gross domestic product (GDP) is essential for better understanding the dynamics of regional economies and urbanization processes. Satellite based nighttime light datasets can well track GDP in urban areas, however, they are difficult to be used in suburban, rural and sparsely populated areas. Thus, this study explored the potential of GlobeLand30 and relief degree for improving the ability of VIIRS Nighttime Light data of GDP estimation. Firstly, we calculated the Moran’s Index (Moran’s I) to measure spatial auto-correlation of GDP. At provincial level, Moran’s I Index of GDP is 0.14, Z value is 2.29. While at the prefecture city level, it is 0.11 and 14.54, respectively. Then, we compared the results derived from geographically weighted regression (GWR) and OLS models (i.e., R2, root mean square error, corrected Akaike information criteria and residuals). Both models suggest that land cover information can significantly improve GDP estimation performance, and total nighttime light (TNL) is the most important economic indicator for estimating GDP. The coefficients of the GWR model for TNL at the provincial and prefecture levels are 1.75 and 1.19, respectively, which are significantly larger than the coefficients for other factors such as land cover and terrain undulation. In addition, the GWR model performed better than OLS model in GDP estimation at both provincial and prefecture levels, and prefecture-level models can better depict the spatial variation in detail. In provincial-level models, GWR could account for 93% of economic development, while OLS could only reflect 82%. Likewise, in prefecture-level models, R2 of GWR model improved almost 50% compared with that of OLS model.

Biochar has been recognised as an efficacious amendment for the remediation of compound heavy metal contamination in soil. However, the molecular mechanism of biochar-mediated tolerance to compound heavy metal toxicity in cotton is unknown. The objective of this research was to investigate the positive impact of biochar (10 g·kg−1) on reducing damage caused by compound heavy metals (Cd, Pb, and As) in cotton (Gossypium hirsutum L.). The results revealed that biochar reduced Cd concentrations by 24.9 % (roots), and decreased Pb concentrations by 37.1 % (roots) and 59.53 % (stems). Biochar maintained ionic homoeostasis by regulating the expression of metal transporter proteins such as ABC, HIPP, NRAMP3, PCR, and ZIP, and genes related to the carbon skeleton and plasma membrane. Biochar also downregulated genes related to photosynthesis, thereby increasing photosynthesis. Biochar re-established redox homoeostasis in cotton by activating signal transduction, which regulated the activity of the enzymes POD, SOD, and CAT activity; and the expression of related genes. This research revealed the molecular mechanism by which biochar confers resistance to the harmful effects of compound heavy metal toxicity in cotton. The application of biochar as a soil amendment to neutralise the toxicity of compound heavy metals is recommended for cash crop production.

Abstract Brown carbon (BrC) exhibits a highly complex chemical composition with diverse light‐absorbing properties, which complicates our understanding of its climate impacts. This study examined the impact of molecular characteristics (including molecular mass, unsaturation, oxidation state, and polarity) and heteroatoms on the light‐absorbing properties (absorptivity and wavelength dependence) of BrC from a molecular perspective, based on the ultraviolet‐visible spectra of over 40,000 light‐absorbing substances in aerosol from different sources and ambience. Our findings reveal that the light‐absorptivity of BrC molecules increases with decreasing polarity and O/C ratio, while it rises with higher molecular mass and unsaturation. We developed predictive models for molecular absorptivity based on its double bond equivalent and O/C ratio. In addition, we observed an inverse correlation between absorptivity and wavelength dependence at the molecular level, as determined through mathematical analysis. This molecular‐level understanding provides valuable insights into BrC absorbing mechanisms, facilitating more accurate characterization in atmospheric models.

Sarez Lake, recognized as the world's highest-altitude dammed lake, necessitates meticulous monitoring of dam deformation, lake water levels, and water storage fluctuations to ensure its safety. In pursuit of this critical objective, a Global Navigation Satellite System (GNSS) monitoring network has been established around the lake to compute real-time station coordinates for deformation monitoring. GNSS Multipath Reflectometry (GNSS-MR) technology has been introduced as an innovative approach, enabling water level retrieval through conventional GNSS geodetic receivers. However, the complex and rugged terrain surrounding Sarez Lake poses challenges to the application of GNSS-MR in this region. This research is dedicated to addressing the challenges posed by the limited available elevation range selection and the retrieval of inter-site water level combinations in such demanding terrain. It proposes a novel method for effectively discerning valid Signal-to-Noise Ratio (SNR) arcs and an inter-site inter-signal water level combination retrieval approach, resulting in a continuous sequence of water level retrievals for this region. The incorporation of remote sensing techniques further facilitates the estimation of water storage fluctuations in the area. The outcomes of this study demonstrate the efficacy of GNSS-MR in capturing the lake's seasonal water-level variations, with retrieval uncertainties ranging from centimeters to low decimeters. The fusion of GNSS-MR with remote sensing data offers a comprehensive approach for monitoring the water levels and water storage fluctuations of Sarez Lake within its challenging environmental conditions. This research provides a valuable methodology applicable to the study and monitoring of other dammed lakes.

Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1–100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future.

Background Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach.Methods In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KD BCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients.Results Compared with parental BCMA CAR-T cells, PD-1KD BCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KD BCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity.Conclusions Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.

Summary: Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The oSVZ comprises progenitor cells expressing specific oRG markers such as GFAP, LIFR, and HOPX, closely matching human fetal oRG. Finally, incorporating neural crest-derived LIF-producing cortical pericytes into cortical organoids recapitulates the effects of LIF treatment. These data indicate that increasing the cellular complexity of the organoid microenvironment promotes the emergence of oRG and supports a platform to study oRG in hPSC-derived brain organoids routinely.

Neuroinflammation and oxidative stress play a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. The triggering receptor expressed on myeloid cells 2 (TREM2), highly expressed by microglia in the central nervous system (CNS), can modulate neuroinflammatory responses. Currently, there are no approved drugs specifically targeting TREM2 for CNS diseases. Aspidosperma alkaloids have shown potential as anti-inflammatory and neuroprotective agents. This study aimed to elucidate the potential therapeutic effect of Hecubine, a natural aspidosperma-type alkaloid, as a TREM2 activator in lipopolysaccharide (LPS)-stimulated neuroinflammation in in vitro and in vivo models. In this study, molecular docking and cellular thermal shift assay (CTSA) were employed to investigate the interaction between Hecubine and TREM2. Enzyme-linked immunosorbent assay (ELISA), quantitative PCR, immunofluorescence, Western blotting, and shRNA gene knockdown were used to assess the anti-neuroinflammatory and antioxidant effects of Hecubine in microglial cells and zebrafish. Our results revealed that Hecubine directly interacted with TREM2, leading to its activation. Knockdown of TREM2 mRNA expression significantly abolished the anti-inflammatory and antioxidant effects of Hecubine on LPS-stimulated proinflammatory mediators (NO, TNF-α, IL-6, and IL-1β) and oxidative stress in microglia cells. Furthermore, Hecubine upregulated Nrf2 expression levels while downregulating TLR4 signaling expression levels both in vivo and in vitro. Silencing TREM2 upregulated TLR4 and downregulated Nrf2 signaling pathways, mimicking the effect of Hecubine, further supporting TREM2 as the drug target by which Hecubine inhibits neuroinflammation. In conclusion, this is the first study to identify a small molecule, namely Hecubine directly targeting TREM2 to mediate anti-neuroinflammation and anti-oxidative effects, which serves as a potential therapeutic agent for the treatment of neural inflammation-associated CNS diseases.

Abstract Common bile duct (CBD) exploration and T-tube drainage are the main surgical methods for the removal of bile duct stones (BDSs), which can now be completed by laparoscopy. However, the feasibility and safety of primary closure of the CBD (PCCBD) in laparoscopic CBD exploration (LCBDE) without biliary drainage are still uncertain. From January 1, 2021, to June 30, 2022, patients who were diagnosed with BDSs and underwent LCBDE and primary closure of the CBD without biliary drainage in our hospital were included. The clinical and prognostic data of the patients were retrospectively analyzed to determine the feasibility and safety of PCCBD in LCBDE without biliary drainage. Forty-nine patients successfully underwent PCCBD in LCBDE without biliary drainage. The operation time was 158.8 ± 50.3 (90–315,150) minutes, the bile duct suture time was 17.6 ± 4.46 (10–26, 18) minutes, the intraoperative blood loss volume was 70.4 ± 52.6 (5–200, 80) ml, the hospitalization cost was 28,141.2 ± 7011.3 (15,005.45–52,959.34, 26,815.14) CNY Yuan, the hospitalization time was 13.22 ± 5.16 (8–32, 12) days, and the postoperative hospitalization time was 7.31 ± 1.94 (3–15, 7) days. There were 3 cases of postoperative bile leakage (3/49, 6.12%), all of them healed by nonsurgical treatment. During the follow-up of 17.2 ± 11.01 (10–26, 17) months, no residual BDSs, biliary stricture or other complications classified as Clavien-Dindo grade I or higher occurred. For some selected patients who meet certain criteria, PCCBD in LCBDE without biliary drainage is feasible and safe and is more conducive to the rapid postoperative recovery of patients.

Laboratory mutants of Sclerotinia sclerotiorum (Lib) de Bary, resistant to boscalid, have been extensively characterized. However, the resistance situation in the lettuce field remains largely elusive. In this study, among the 172 S. sclerotiorum isolates collected from asparagus lettuce field in Jiangsu Province, China, 132 isolates (76.74%) exhibited low-level resistance to boscalid (BosLR), with a discriminatory dose of 5 μg mL−1. In comparison to the boscalid-sensitive (BosS) isolates, most BosLR isolates demonstrated a slightly superior biological fitness, as evidenced by data on mycelial growth, sclerotium production and pathogenicity. Moreover, most BosLR isolates showed comparable levels of oxalic acid (OA) accumulation, increased exopolysaccharide (EPS) content and reduced membrane permeability when compared to the BosS isolates. Nevertheless, their responses to distinct stress factors diverged significantly. Furthermore, the effectiveness of boscalid in controlling BosLR isolates on radish was diminished compared to its efficacy on BosS isolates. Genetic mutations were identified in the SDH genes of BosLR isolates, revealing the existence of three resistant genotypes: I (A11V at SDHB, SDHBA11V), II (Q38R at SDHC, SDHCQ38R) and III (SDHBA11V+SDHCQ38R). Importantly, no cross-resistance was observed between boscalid and other fungicides such as thifluzamide, pydiflumetofen, fluazinam, or tebuconazole. Our molecular docking analysis indicated that the docking total score (DTS) of the type I resistant isolates (1.3993) was lower than that of the sensitive isolates (1.7499), implying a reduced affinity between SDHB and boscalid as a potential mechanism underlying the boscalid resistance in S. sclerotiorum. These findings contribute to an enhanced comprehension of boscalid’s mode of action and furnish valuable insights into the management of boscalid resistance.

Abstract Background With the COVID-19 outbreak, an increasing number of individuals are concerned about their health, particularly their immune status. However, as of now, there is no available algorithm that effectively assesses the immune status of normal, healthy individuals. In response to this, a new score-based method is proposed that utilizes complete blood cell counts (CBC) to provide early warning of disease risks, such as COVID-19. Methods First, data on immune-related CBC measurements from 16,715 healthy individuals were collected. Then, a three-platform model was developed to normalize the data, and a Gaussian mixture model was optimized with expectation maximization (EM-GMM) to cluster the immune status of healthy individuals. Based on the results, Random Forest (RF), Light Gradient Boosting Machine (LightGBM) and Extreme Gradient Boosting (XGBoost) were used to determine the correlation of each CBC index with the immune status. Consequently, a weighted sum model was constructed to calculate a continuous immunity score, enabling the evaluation of immune status. Results The results demonstrated a significant negative correlation between the immunity score and the age of healthy individuals, thereby validating the effectiveness of the proposed method. In addition, a nonlinear polynomial regression model was developed to depict this trend. By comparing an individual’s immune status with the reference value corresponding to their age, their immune status can be evaluated. Conclusion In summary, this study has established a novel model for evaluating the immune status of healthy individuals, providing a good approach for early detection of abnormal immune status in healthy individuals. It is helpful in early warning of the risk of infectious diseases and of significant importance.

AbstractBackground Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased risk of death, but its underlying mechanisms are not fully understood. Circular RNAs (circRNAs) have recently been implicated in various biological processes. The aim of this study was to investigate the key circRNAs related to RA.Methods A microarray assay was used to identify the differentially expressed circRNAs (DEcircRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with RA compared to patients with osteoarthritis (OA) and healthy controls. Then, quantitative real-time PCR was applied to verify the DEcircRNAs, and correlations between the levels of DEcircRNAs and laboratory indices were analysed. We also performed extensive bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and potential circRNA–miRNA–mRNA network analyses to predict the function of these DEcircRNAs.Results A total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR. There were correlations between the levels of DEcircRNAs and some of the laboratory indices. GO analyses revealed that these DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, cell cycle, posttranslational protein modification and collagen formation. Functional annotation of host genes of these DEcircRNAs was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, the AMPK signalling pathway, leukocyte transendothelial migration, platelet activation and the cAMP signalling pathway, which might be responsible for the pathophysiology of RA.Conclusions The findings of this study may help to elucidate the role of circRNAs in the specific mechanism underlying RA.Key messagesMicroarray assays showed that a total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively.Nine out of the DEcircRNAs in RA were validated by real-time PCR, and the levels of the DEcircRNAs were related to some of the laboratory indices.GO analyses revealed that the DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, etc.Functional annotation of host genes of the DEcircRNAs in RA was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, etc.

Abstract Background The relationship between tea and coffee consumption and mortality among patients with metabolic syndrome (MetS) remains barely explored. Herein, this study aimed to examine the association between tea and coffee consumption and the likelihood of all-cause and cause-specific mortality in patients with MetS. Methods A total of 118,872 participants with MetS at baseline from the UK Biobank cohort were included. Information on tea and coffee consumption was obtained during recruitment using a touchscreen questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were determined using Cox proportional hazards models. Results During a median follow-up of 13.87 years, 13,666 deaths were recorded, with 5913, 3362, and 994 deaths from cancer, cardiovascular diseases (CVD), and respiratory disease (RD), respectively. This research showed a significant inverse association between tea intake and the risk of all-cause and cancer mortality, the respective HRs (95% CI) for consuming tea 2 vs. 0 cup/day were 0.89 (0.84–0.95), and 0.91 (0.83–0.99), and tea intake ≥ 4 cups/day could reduce CVD mortality by 11% (HR 0.89; 95% CI 0.81–0.98). The U-shaped nonlinear association between coffee intake and all-cause/CVD mortality was examined (all p-nonlinear

Abstract An experimental investigation of circular concrete-filled steel tubular (CFST) columns subjected to very low-elevation lateral impacts was performed. Six circular CFST members were prepared for lateral impact tests according to the typical CFST columns in high-speed railway stations in China, and the impact location was at the height of the 2/9 column. The tests had three variables: the thickness of the steel tube, the impact velocity, and the axial load. The failure modes were determined in the tests, along with the time histories of the impact force and the deflection at the impact location. A finite-element analysis was performed to examine the effects of the axial load and scaling on the maximum deflection. The results show that with the increase of axial compression ratio, the impact resistance of the member first increases and then weakens. According to the travelling plastic hinge theory, a three-stage rigid plastic mechanical model was employed to describe the impact process, in which the impact location was at the non-mid-span, and a deflection calculation method for CFST applicable to any impact position was developed. A comparison with the test results indicated that deflections can be calculated with reasonable accuracy using the proposed method.

Abstract Urban land will face high fluvial flood risk against the background of climate change and urban expansion. The effect of urban spatial expansion, instead of densification of assets within existing urban cells, on flood risk has rarely been reported. Here, we project the future flood risk of seven urban agglomerations in China, home to over 750 million people. The inundated urban land areas in the future are projected to be 4 to 19 times that at present. Without considering the urban spatial expansion, the inundated urban land areas will be underestimated by 10-50%. Urban land is more likely to be inundated than non-urban land, and the newly-developed urban land will be inundated more easily than the historical urban land. The results demonstrate the urgency of integrating climate change mitigation, reasonable urban land expansion, and increased flood protection levels to minimize the flood risk in urban land.

Abstract Background Hypertension caused by air pollution exposure is a growing concern in China. The association between air pollutant exposure and hypertension has been found to be potentiated by obesity, however, little is known about the processes mediating this association. This study investigated the association between fine particulate matter (aerodynamic equivalent diameter ≤ 2.5 microns, PM2.5) exposure and the prevalence of hypertension in a representative population in southern China and tested whether obesity mediated this association. Methods A total of 14,308 adults from 48 communities/villages in southern China were selected from January 2015 to December 2015 using a stratified multistage random sampling method. Hourly PM2.5 measurements were collected from the China National Environmental Monitoring Centre. Restricted cubic splines were used to analyze the nonlinear dose-response relationship between PM2.5 exposure and hypertension risk. The mediating effect mechanism of obesity on PM2.5-associated hypertension was tested in a causal inference framework following the approach proposed by Imai and Keele. Results A total of 20.7% (2966/14,308) of participants in the present study were diagnosed with hypertension. Nonlinear exposure-response analysis revealed that exposure to an annual mean PM2.5 concentration above 41.8 µg/m3 was associated with increased hypertension risk at an incremental gradient. 9.1% of the hypertension burden could be attributed to exposure to elevated annual average concentrations of PM2.5. It is noteworthy that an increased body fat percentage positively mediated 59.3% of the association between PM2.5 exposure and hypertension risk, whereas body mass index mediated 34.3% of this association. Conclusions This study suggests that a significant portion of the estimated effect of exposure to PM2.5 on the risk of hypertension appears to be attributed to its effect on alterations in body composition and the development of obesity. These findings could inform intersectoral actions in future studies to protect populations with excessive fine particle exposure from developing hypertension.

Building height is a crucial indicator when studying urban environments and human activities, necessitating accurate, large-scale, and fine-resolution calculations. However, mainstream machine learning-based methods for inferring building heights face numerous challenges, including limited sample data and slow update frequencies. Alternatively, satellite laser altimetry technology offers a reliable means of calculating building heights with high precision. Here, we initially calculated building heights along satellite orbits based on building-rooftop contour vector datasets and ICESat-2 ATL03 photon data from 2019 to 2022. By integrating multi-source passive remote sensing observation data, we used the inferred building height results as reference data to train a random forest model, regressing building heights at a 10 m scale. Compared with ground-measured heights, building height samples constructed from ICESat-2 photon data outperformed methods that indirectly infer building heights using total building floor number. Moreover, the simulated building heights strongly correlated with actual observations at a single-city scale. Finally, using several years of inferred results, we analyzed building height changes in Tianjin from 2019 to 2022. Combined with the random forest model, the proposed model enables large-scale, high-precision inference of building heights with frequent updates, which has significant implications for global dynamic observation of urban three-dimensional features.

The estimation of energy consumption under real-world driving conditions is a prerequisite for optimizing bus scheduling and meeting the requirements of route operation, thereby promoting the large-scale application of battery electric buses. However, the limitation of data accuracy and the uncertainty of many factors, such as weather conditions, traffic conditions, and driving styles, etc. make accurate energy consumption estimation complicated. In response to these challenges, a new method for estimating the energy consumption of battery electric buses (BEBs) is proposed in this research. This method estimates the speed profiles of different driving styles and the energy consumption extremes using real-world driving data. First, this research provides the constraints on speed formed by environmental factors including weather conditions, route characteristics, and traffic characteristics. On this basis, there are two levels of estimation for energy consumption. The first level classifies different driving styles and constructs the corresponding speed profiles with the time interval (10 s), the same as real-world driving data. The second level further constructs the speed profiles with the time interval of 1 s by filling in the first-level speed profiles and estimating the energy consumption extremes. Finally, the estimated maximum and minimum value of energy consumption were compared with the true value and the results showed that the real energy consumption did not exceed the extremes we estimated, which proves the method we proposed is reasonable and useful. Therefore, this research can provide a theoretical foundation for the deployment of battery electric buses.

The heart and brain are the core organs of the circulation and central nervous system, respectively, and play an important role in maintaining normal physiological functions. Early neuronal and cardiac damage affects organ function. The relationship between the heart and brain is being continuously investigated. Evidence-based medicine has revealed the concept of the “heart- brain axis,” which may provide new therapeutic strategies for certain diseases. Takeda protein-coupled receptor 5 (TGR5) is a metabolic regulator involved in energy homeostasis, bile acid homeostasis, and glucose and lipid metabolism. Inflammation is critical for the development and regeneration of the heart and brain during metabolic diseases. Herein, we discuss the role of TGR5 as a metabolic regulator of heart and brain development and injury to facilitate new therapeutic strategies for metabolic and ischemic diseases of the heart and brain.

Cardiac arrhythmias are often linked to the overactivity of cardiac fibroblasts (CFs). Investigating the impact of poly (ADP-ribose) polymerase 9 (PARP9) on Angiotensin II (Ang II)-induced fibroblast activation and the therapeutic effects of pirfenidone (PFD) offers valuable insights into cardiac arrhythmias. This study utilized weighted gene co-expression network analysis (WGCNA), differential gene expression (DEG) analysis, protein-protein interaction (PPI), and receiver operating characteristic (ROC) analysis on the GSE42955 dataset to identify the hub gene with significant diagnostic value. The ImmuCellAI tool revealed an association between PARP9 and immune cell infiltration. Our in vitro assessments focused on the influence of PFD on myofibroblast differentiation, TGF-β expression, and Ang II-induced proliferation and migration in CFs. Additionally, we explored the impact on fibrosis markers and the TGF-β/Smad signaling pathway in the context of PARP9 overexpression. Analysis of the GSE42955 dataset revealed PARP9 as a central gene with high clinical diagnostic value, linked to seven types of immune cells. The in vitro studies demonstrated that PFD significantly mitigates Ang II-induced CF proliferation, migration, and fibrosis. It also reduces Ang II-induced PARP9 expression and decreases fibrosis markers, including TGF-β, collagen I, collagen III, and α-SMA. Notably, PARP9 overexpression can partially counteract PFD's inhibitory effects on CFs and modify the expression of fibronectin, CTGF, α-SMA, collagen I, collagen III, MMP2, MMP9, TGF-β, and p-Smad2/3 in the TGF-β/Smad signaling pathway. In summary, our findings suggestes that PFD effectively counteracts the adverse effects of Ang II-induced CF proliferation and fibrosis, and modulates the TGF-β/Smad signaling pathway and PARP9 expression. This identifies a potential therapeutic approach for managing myocardial fibrosis.

The emerging fluoroquinolone antibiotics (FQs) are highly influential in nitrogen removal from livestock wastewater. However, beyond the capability of nitrogen removal, little is known about the molecular mechanisms (e.g., shift of core metabolism and energy allocation) of different anaerobic ammonium-oxidizing bacteria (AnAOB) under continuous FQ stress. This study investigated the effects of ciprofloxacin, ofloxacin and their mixture at concentrations detected in livestock wastewater on two key anammox species in membrane bioreactors. It was found 20 μg/L FQs promoted nitrogen removal efficiency and community stability, and42–51 % of FQs were removed simultaneously. Integrated meta-omics analysis revealed varied gene expression patterns between the two dominant AnAOB, Candidatus Brocadia sapporoensis (B AnAOB) and Candidatus Kuenenia stuttgartiensis (K AnAOB). The nitrogen metabolic processes were bolstered in B AnAOB, while those involved in anammox pathway of K AnAOB were inhibited. This difference was tentatively attributed to the up-regulation of reactive oxygen species scavenger genes (ccp and dxf) and FQ resistance gene (qnrB72) in B AnAOB. Importantly, most enhanced core biosynthesis/metabolism of AnAOB and close cross-feeding with accompanying bacteria were also likely to contribute to their higher levels of biomass yield and metabolism activity under FQ stress. This finding suggests that B AnAOB has the advantage of higher nitrogen metabolism capacity over K AnAOB in livestock wastewater containing FQs, which is helpful for efficient and stable nitrogen removal by the functional anammox species.

Australian Mandarin-English bilingual preschoolers must acquire linguistic structures that occur only in the community language (e.g., English inflectional grammar). This study investigated how they acquire such structures and any relationship between linguistic knowledge and language experience on their performance. Twenty 4–6-year-olds showed known monolingual acquisition patterns with good performance for producing the progressive, developing ability for plurals, but only emerging ability for past and present tense. Better performance was related to a larger English vocabulary, more mixed language input and use, but less Mandarin input and use. On average, these children received less than 50% input in English and were performing behind monolinguals.

IntroductionGlobal climate change exerts a significant impact on the nitrogen supply and photosynthesis ability in land-based plants. The photosynthetic capacity of dominant grassland species is important if we are to understand carbon cycling under climate change. Drought stress is one of the major factors limiting plant photosynthesis, and nitrogen (N) is an essential nutrient involved in the photosynthetic activity of leaves. The regulatory mechanisms responsible for the effects of ammonium (NH4+) and nitrate (NO3-) on the drought-induced photoinhibition of photosystem II (PSII) in plants have yet to be fully elucidated. Therefore, there is a significant need to gain a better understanding of the role of electron transport in the photoinhibition of PSII.MethodsIn the present study, we conducted experiments with normal watering (LD), severe drought (MD), and extreme drought (HD) treatments, along with no nitrogen (N0), ammonium (NH4), nitrate (NO3), and mixed nitrogen (NH4NO3) treatments. We analyzed pigment accumulation, reactive oxygen species (ROS) accumulation, photosynthetic enzyme activity, photosystem activity, electron transport, and O-J-I-P kinetics.ResultsAnalysis showed that increased nitrate application significantly increased the leaf chlorophyll content per unit area (Chlarea) and nitrogen content per unit area (Narea) (p< 0.05). Under HD treatment, ROS levels were lower in NO3-treated plants than in N0 plants, and there was no significant difference in photosynthetic enzyme activity between plants treated with NO3 and NH4NO3. Under drought stress, the maximum photochemical efficiency of PSII (Fv/Fm), PSII electron transport rate (ETR), and effective quantum yield of PSII (φPSII) were significant higher in NO3-treated plants (p< 0.05). Importantly, the K-band and G-band were higher in NO3-treated plants.DiscussionThese results suggest that drought stress hindered the formation of NADPH and ATP in N0 and NH4-treated L. chinensis plants, thus damaging the donor side of the PSII oxygen-evolving complex (OEC). After applying nitrate, higher photosynthetic enzyme and antioxidant enzyme activity not only protected PSII from photodamage under drought stress but also reduced the rate of damage in PSII during the growth of L. chinensis growth under drought stress.

BackgroundKounis syndrome is an acute coronary syndrome (ACS) caused by allergic reactions, including coronary artery spasm (type I) caused by allergies without coronary predisposing factors, pre-existing coronary atherosclerosis, and coronary artery disease. Anaphylaxis leads to plaque rupture or erosion leading to acute myocardial infarction (type II) and acute coronary stent thrombosis (type III). Here we share a case of Kounis syndrome type I caused by an allergy caused by a Cryptopteran bite.Case presentationA 47-year-old woman was admitted to the hospital due to an insect bite for 2 days and chest distress for more than 3 h. Outside the hospital, electrocardiogram(ECG) showed sinus rhythm, ST-segment elevation in leads V1–V3, high-sensitivity troponin 2.54 ng/ml(0–0.5 ng/ml). One hour later, the ECG of the patient showed that the ST segment elevation of lead V1–V4 was 0.10–0.20 mV. Emergency coronary angiography showed coronary spasm and moderate lumen stenosis in the middle segment of left anterior descending artery (LAD). After treatment, the patient's symptoms were relieved, and the ST segment of lead V1–V4 of electrocardiogram returned to normal.ConclusionKunis syndrome is a life-threatening condition that can also cause myocardial ischemic injury in patients with or without coronary artery disease. Timely identification and anti-allergic treatment can achieve a good prognosis.

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients’ clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia.Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice.Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect.Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD’s maximal therapeutic response, there existed a hysteresis. WDD’s effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats.Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.

Purpose: The aim of this study is to investigate a new method that combines radiological and pathological breast cancer information to predict discrepancies in pathological responses for individualized treatment planning. We used baseline multiparametric magnetic resonance imaging and hematoxylin and eosin-stained biopsy slides to extract quantitative feature information and predict the pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively collected data from breast cancer patients who received neoadjuvant chemotherapy in our hospital from August 2016 to January 2018; multiparametric magnetic resonance imaging (contrast-enhanced T1-weighted imaging and diffusion-weighted imaging) and whole slide image of hematoxylin and eosin-stained biopsy sections were collected. Quantitative imaging features were extracted from the multiparametric magnetic resonance imaging and the whole slide image were used to construct a radiopathomics signature model powered by machine learning methods. Models based on multiparametric magnetic resonance imaging or whole slide image alone were also constructed for comparison and referred to as the radiomics signature and pathomics signature models, respectively. Four modeling methods were used to establish prediction models. Model performances were evaluated using receiver operating characteristic curve analysis and the area under the curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: The radiopathomics signature model had favourable performance for the prediction of pathological complete response in the training set (the best value: area under the curve 0.83, accuracy 0.84, and sensitivity 0.87), and in the test set (the best value: area under the curve 0.91, accuracy 0.90, and sensitivity 0.88). In the test set, the radiopathomics signature model also significantly outperformed the radiomics signature (the best value: area under the curve 0.83, accuracy 0.64, and sensitivity 0.62), pathomics signature (the best value: area under the curve 0.60, accuracy 0.74, and sensitivity 0.62) (p > 0.05). Decision curve analysis and calibration curves confirmed the excellent performance of these prediction models in discrimination, calibration, and clinical usefulness. Conclusions: The results of this study suggest that radiopathomics, the combination of both radiological information regarding the whole tumor and pathological information at the cellular level, could potentially predict discrepancies in pathological response and provide evidence for rational treatment plans.

Abstract Excitons, which represent a type of quasi-particles consisting of electron-hole pairs bound by the mutual Coulomb interaction, are often observed in lowly-doped semiconductors or insulators. However, realizing excitons in semiconductors or insulators with high charge-carrier densities is challenging. Here, we perform infrared spectroscopy, electrical transport, ab initio calculations, and angle-resolved-photoemission spectroscopy study of the van der Waals degenerate-semiconductor Bi4O4SeCl2. A peak-like feature (α peak) is present around ~125 meV in the optical conductivity spectra at low temperature T = 8 K and room temperature. After being excluded from the optical excitations of free carriers, interband transitions, localized states and polarons, the α peak is assigned as an exciton absorption. Assuming the existence of weakly-bound Wannier-type excitons in this material violates the Lyddane-Sachs-Teller relation. Moreover, the exciton binding energy of ~375 meV, which is about an order of magnitude larger than those of conventional semiconductors, and the charge-carrier concentration of ~1.25 × 1019 cm−3, which is higher than the Mott density, further indicate that the excitons in this highly-doped system should be tightly bound. Our results pave the way for developing optoelectronic devices based on tightly bound and room-temperature-stable excitons in highly-doped van der Waals degenerate semiconductors.