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Abstract Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z 2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

Abstract Background Patients with choriocarcinoma (CC) accompanying chemoresistance conventionally present a poor prognosis. Whether ras protein activator like-1 (RASAL1) functions as a tumor promoter or suppressor depends on tumor types. However, the role of RASAL1 in process of chemoresistance of CC and underlying molecular mechanism remain elusive. Methods The expression pattern of RASAL1 in CC cells and tissues was measured using Western blotting, immunohistochemistry and qRT-PCR. Cell viability and proliferative ability were assessed by MTT assay, Tunnel assay and flow cytometric analysis. Additionally, the stemness was evaluated by the colony formation and tumor sphere formation. Methotrexate (MTX) was applied to exam the chemosensitivity of CC cells. Results The expression of RASAL1 was reduced both at the protein and mRNA levels in CC tissues and cells compared to hydatidiform mole (HM) and invasive mole (IM). Loss of RASAL1 was attributed to its promoter hypermethylation and could be restored by 5-Aza. Knock-down of RASAL1 promoted the viability, proliferative potential, stemness and EMT phenotype of JEG-3 cells. However, induced overexpression of RASAL1 by 5-Aza significantly prohibited cell proliferation and stemness potential of the JAR cell. Additionally, the xenograft model indicated that knockdown of RASAL1 led to a remarkable increase of tumor volume and weight in comparison with its counterpart. Moreover, the stimulatory activity brought by decrease of RASAL1 could be deprived by β-catenin inhibitor XAV 939, yet the suppressive activity resulted from its promoter demethylation could be rescued by β-catenin activator BML-284, indicating that function of RASAL1 depends on β-catenin. Besides, the co-immunoprecipitation assay confirmed the physical binding between RASAL1 and β-catenin. Further investigations showed hypermethylated RASAL1 was regulated by TET2 but not DNMTs. Conclusion Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating β-catenin both in vitro and in vivo.

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. However, the relationship between core stability and the effectiveness of athletic performance, particularly in executing the wing kick, remains ambiguous, impeding coaches and athletes in their efforts to improve athletic performance. A total of 26 male participants (height: 167.21 ± 7.29 cm; weight: 62.07 ± 8.03 kg; age: 24.69 ± 2.53 years) participated, and they have been practicing Taekwondo for more than 10 years. Kinematic and kinetic data were collected using 13 infrared cameras at 120 Hz, muscle activity data were collected using epidermal electromyography, and participants’ core stability level were measured using the Sahrmann Core Stability Test (SCST) for correlation with other variables. Core stability levels showed a strong negative correlation with execution time (r = −0.7144, p < 0.001) of the aerial phase of the wing kick as did angular momentum in most lower limb segments (thigh X axis, r = −0.6435, p < 0.001, shank X axis, r = −0.62008, p < 0.001, foot X axis, r = −0.7033, p < 0.001). Bilateral rectus abdominis (RA) showed strong correlations with muscle activation (left rectus abdominis (LRA) of left foot take off-left knee max extension (LTO-LKMF) phase, r = 0.5351, p < 0.001, right rectus abdominis (RRA) of LTO-LKMF phase, r = −0.5628, p < 0.001), and high levels of core stability were associated with better core-muscle coupling. We conclude that incorporating core stability training into taekwondo training has the potential to improve wing kick performance.

Abstract The triglyceride-glucose (TyG) index is a novel marker of insulin resistance that has been strongly associated with many diseases related to metabolic disorders, such as diabetes, coronary heart disease, myocardial infarction, obesity, nonalcoholic fatty liver disease, and stroke. However, whether the TyG index is associated with the prevalence of gallstones has not been determined. Therefore, the purpose of this study was to evaluate the relationship between the TyG index and the prevalence of gallstones in American adults, as well as the age at which adults in America undergo their first gallstone surgery. We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to March 2020. Based on the goal of our study, comprehensive inclusion and exclusion criteria were created. A logistic regression analysis, dose–response curve, and subgroup analysis were computed to assess the relationship between the TyG index and gallstone prevalence and age at first surgery for gallstone. A total of 3905 participants aged > 20 years were included in our study, of whom 421 had a self-reported history of gallstones. A total of 1884 (48.2%) males and 2021 (51.8%) females were included. After confounders adjustment, it was found single-unit increases in the TyG index were linked with a 25.0% increase in gallstone prevalence (odds ratio [OR] = 1.25, 95% confidence interval [95%CI]: 1.04, 1.51). After conversion of the TyG index values from continuous to categorical variables with tertiles, a marked 48% increase in gallstone incidence was found in tertile 3 relative to tertile 1 (OR = 1.48, 95% CI: 1.09, 1.99). The dose–response curve results indicated positive associations between gallstone prevalence and the TyG index, while the latter was negatively associated with age at first gallstone surgery. Based on subgroup analysis, the positive association between TyG index and high-incidence of gallstones was more significant in females (OR = 1.39, 95% CI: 1.09, 1.77), age

Abstract Background The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments. Methods The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized. Results Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2. Conclusions Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

Abstract Background Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15–39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). Result In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. Conclusion ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

The global COVID-19 pandemic has severely impacted human health and socioeconomic development, posing an enormous public health challenge. Extensive research has been conducted into the relationship between environmental factors and the transmission of COVID-19. However, numerous factors influence the development of pandemic outbreaks, and the presence of confounding effects on the mechanism of action complicates the assessment of the role of environmental factors in the spread of COVID-19. Direct estimation of the role of environmental factors without removing the confounding effects will be biased. To overcome this critical problem, we developed a Double Machine Learning (DML) causal model to estimate the debiased causal effects of the influencing factors in the COVID-19 outbreaks in Chinese cities. Comparative experiments revealed that the traditional multiple linear regression model overestimated the impact of environmental factors. Environmental factors are not the dominant cause of widespread outbreaks in China in 2022. In addition, by further analyzing the causal effects of environmental factors, it was verified that there is significant heterogeneity in the role of environmental factors. The causal effect of environmental factors on COVID-19 changes with the regional environment. It is therefore recommended that when exploring the mechanisms by which environmental factors influence the spread of epidemics, confounding factors must be handled carefully in order to obtain clean quantitative results. This study offers a more precise representation of the impact of environmental factors on the spread of the COVID-19 pandemic, as well as a framework for more accurately quantifying the factors influencing the outbreak.

The increasing interest in multilineage differentiating stress-enduring (Muse) cells within the field of regenerative medicine is attributed to their exceptional homing capabilities, prolonged viability in adverse conditions, and enhanced three-germ-layer differentiate ability, surpassing their parent mesenchymal stem cells. Given their abundant sources, non-invasive collection procedure, and periodic availability, human menstrual blood-derived endometrium stem cells (MenSCs) have been extensively investigated as a potential resource for stem cell-based therapies. However, there is no established modality to isolate Muse cells from MenSCs and disparity in gene expression profiles between Muse cells and MenSCs remain unknown. In this study, Muse cells were isolated from MenSCs by long-time trypsin incubation method. Muse cells expressed pluripotency markers and could realize multilineage differentiation in vitro. Compared with MenSCs, Muse cells showed enhanced homing ability and superior therapeutic efficacy in animal models of acute liver injury (ALI) and intracerebral hemorrhage (ICH). Furthermore, the RNA-seq analysis offers insights into the mechanism underlying the disparity in trypsin resistance and migration ability between Muse and MenSCs cells. This research offers a significant foundation for further exploration of cell-based therapies using MenSCs-derived Muse cells in the context of various human diseases, highlighting their promising application in the field of regenerative medicine.

Abstract Background Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain. Methods This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve. Results During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P

Abstract Assimilatory nitrate reduction and methane (CH4) oxidation by bacteria play important roles in carbon (C) and nitrogen (N) biogeochemical cycles. Here, an investigation of enzymatic assimilatory nitrate reduction and CH4 oxidation by Methylobacter sp. YHQ from the wetlands is presented, specifically concentrating on N and oxygen (O) isotope fractionation with various initial nitrate and oxygen concentrations. The N enrichment factors (15 ε assimilation) increased from 4.2 ± 0.7‰ to 6.9 ±1.3‰ and the O isotope enrichment factors (18 ε assimilation) increased from 2.7 ± 0.9‰ to 4.7 ± 0.8‰ during nitrate assimilation when initial nitrate concentrations increased from 0.9 mM to 2 mM. Similar 18 ε and 15 ε values were observed at different oxygen concentrations. The values of 18 ε and 15 ε provided vital parameters for the assessment of assimilatory nitrate reduction via the Rayleigh equation approach. The ratios of O and N isotope enrichment factors (18 ε:15 ε)assimilation ranged from 0.64 ± 0.15 to 0.74 ± 0.18 during nitrate assimilation by Methylobacter sp. YHQ with Nas, which were different from (18 ε:15 ε)assimilation for assimilatory eukaryotic nitrate reductase (eukNR) from literature data. Thus, N and O isotope fractionation could be useful tools to distinguish eukNR from Nas during nitrate assimilation. Additionally, the rates of CH4 oxidation and nitrate reduction were evaluated with a reaction-based kinetic model, and it quantitatively described the enzymatic reactions of nitrate assimilation. Combining dual N-O isotope analysis with kinetic modeling provides new insights into the microbially driven C-N interactions. Graphical Abstract

Abstract Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2−) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2− breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2− breast cancer patients.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (DosR), White B-like (Wbl) family, Toxin-Antitoxin (TA) systems, sigma factors, and MprAB. We outline the progress in vaccine and drug development associated with Mtb dormancy.

Based on the data of outcrop, core, logging, gas testing, and experiments, the natural gas accumulation and aluminous rock mineralization integrated research was adopted to analyze the controlling factors of aluminous rock series effective reservoirs in the Ordos Basin, NW China, as well as the configuration of coal-measure source rocks and aluminous rock series reservoirs. A natural gas accumulation model was constructed to evaluate the gas exploration potential of aluminous rock series under coal seam in the basin. The effective reservoirs of aluminous rock series in the Ordos Basin are composed of honeycomb-shaped bauxites with porous residual pisolitic and detrital structures, with the diasporite content of greater than 80% and dissolved pores as the main storage space. The bauxite reservoirs are formed under a model that planation controls the material supply, karst paleogeomorphology controls diagenesis, and land surface leaching improves reservoir quality. The hot humid climate and sea level changes in the Late Carboniferous–Early Permian dominated the development of a typical coal-aluminum-iron three-stage stratigraphic structure. The natural gas generated by the extensive hydrocarbon generation of coal-measure source rocks was accumulated in aluminous rock series under the coal seam, indicating a model of hydrocarbon accumulation under the source. During the Upper Carboniferous–Lower Permian, the relatively low-lying area on the edge of an ancient land or island in the North China landmass was developed. The gas reservoirs of aluminous rock series, which are clustered at multiple points in lenticular shape, are important new natural gas exploration fields with great potential in the Upper Paleozoic of North China Craton.

Abstract Background Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. Methods This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. Results During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27). Conclusions Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Objective To explore the impacts of health empowerment model combined with binary coping intervention on neurological function,coping style,and hope level in elderly stroke patients. Methods A total of 144 elderly stroke patients admitted to Handan Central Hospital from October 2020 to October 2022 were selected as the research subjects,they were randomly separated into a reference group and an observation group,with 72 cases in each group.The reference group received routine nursing intervention,while observation group received health empowerment combined with binary coping intervention,The neurological function [National Institutes of Health Stroke Scale(NIHSS)] ,coping style [Simplified coping style questionnaire(SCSQ)] ,and hope level [Herth hope index(HHI)] of both groups were evaluated before and after intervention. Results There was no statistically significant difference in NIHSS scores,SCSQ scores,and HHI scores between the two groups before intervention(P>0.05).After intervention,the NIHSS scores of the observation group were lower than those in the control group(P

Abstract In agricultural production activities, the growth of crops always accompanies the competition of weeds for nutrients and sunlight. In order to mitigate the adverse effects of weeds on yield, we apply semantic segmentation techniques to differentiate between seedlings and weeds, leading to precision weeding. The proposed EPAnet employs a loss function coupled with Cross-entropy loss and Dice loss to enhance attention to feature information. A multi-Decoder cooperative module based on ERFnet is designed to enhance information transfer during feature mapping. The SimAM is introduced to enhance position recognition. DO-CONV is used to replace the traditional convolution Feature Pyramid Networks (FPN) connection layer to integrate feature information, improving the model’s performance on leaf edge processing, and is named FDPN. Moreover, the Overall Accuracy has been improved by 0.65%, the mean Intersection over Union (mIoU) by 1.91%, and the Frequency-Weighted Intersection over Union (FWIoU) by 1.19%. Compared to other advanced methods, EPAnet demonstrates superior image segmentation results in complex natural environments with uneven lighting, leaf interference, and shadows.

Abstract Mine water inrush is a serious threat to mine safety production. It is very important to identify water inrush source types quickly to prevent and control water damage. In this study, the aqueous chemical components Na+ + K+, Ca2+, Mg2+, Cl−, SO4 2− and HCO3− of different aquifers in Pingdingshan coalfield were selected as the characteristic values, and the Surface water, Quaternary pore water, Carboniferous limestone karst water, Permian sandstone water, and Cambrian limestone karst water were used as the labels. An intelligent water source discrimination model is proposed by combining data mining, classification models, and reinforcement learning. As outlier data in the samples may interfere with the model recognition ability, the data distribution range was analyzed using box plots, and 20 groups of abnormal samples were excluded. The processed water chemistry data were divided into 80% learning samples and 20% test samples, and the learning samples were fed into a light gradient boosting machine (LightGBM) for training. The tree-structured parson estimator (TPE) obtains the optimal values of the main parameters of LightGBM in a very short time. Substituting the hyperparameters back into the model yields a 13.9% improvement in the accuracy of the model, proving the effectiveness of the TPE algorithm. To further validate the performance of the model, TPE-LightGBM is compared and analyzed with a Random Search-Multi Layer Perceptron Machine (RS-MLP) and Genetic Algorithm-Extreme Gradient Boosting Tree (GA-SVM). The accuracy of TPE-LightGBM, RS-MLP, and GA-SVM is 0.931, 0.759, 0.724 in that order, and the generalization error RMSE is 0.415, 1.05, and 1.313 in that order. The results show that TPE-LightGBM is more advantageous in water source identification and is more resistant to overfitting. By calculating and comparing the information gain of each variable, the contribution of Ca2+ is the highest, so it is necessary to pay attention to the change in Ca2+ concentration. TPE-LightGBM’s high accuracy and generalization ability have a good prospect for the identification of sudden water source types.

Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.

Abstract Background As one of the most famous natural products, salvianolic acid A (SAA) is undergoing clinical trials for the treatments of angina pectoris and coronary heart disorders. However, the in vivo metabolites of SAA have only been tentatively identified, leading to a barrier for precise therapeutical drug monitoring. Methods Ultra-high performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry (UPLC–Qtof-MS/MS) was firstly employed to acquire high-resolution MS1 and MS2 spectra for all metabolites. Through paying special attention onto the features of ester bond dissociation, metabolism sites were restricted at certain regions. To further determine the metabolism site, such as the monomethylated products (M23, M25, and M26), post collision-induced dissociation energy-resolved mass spectrometry (post-CID ER-MS) was proposed through programming progressive exciting energies to the second collision chamber of hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS) device. Results After SAA oral administration, 29 metabolites (M1–M29), including five, thirteen, and sixteen ones in rat plasma, urine, and feces, respectively, were detected in rats. The metabolism route was initially determined by applying well-defined mass fragmentation pathways to those HR-m/z values of precursor and fragment ions. Metabolism site was limited to SAF- or DSS-unit based on the fragmentation patterns of ester functional group. Through matching the dissociation trajectories of concerned 1st-generation fragment ions with expected decomposition product anions using post-CID ER-MS strategy, M23 and M25 were unequivocally assigned as 3'-methyl-SAA and 3''-methyl-SAA, and M26 was identified as 2-methyl-SAA or 3-methyl-SAA. Hydrolysis, methylation, glucuronidation, sulfation, and oxidation were the primary metabolism channels being responsible for the metabolites' generation. Conclusion Together, the metabolism regions and sites of SAA metabolites were sequentially identified based on the ester bond dissociation features and post-CID ER-MS strategy. Importantly, the present study provided a promising way to elevate the structural identification confidence of natural products and metabolites. Graphical abstract

Abstract Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer’s development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN’s pivotal role in tamoxifen resistance. Furthermore, the Kruskal–Wallis rank test indicated UTRN’s potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN’s close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN’s role in breast cancer’s prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

Abstract Background Medial patellar ligament reconstruction (MPFL-R) in combination with derotational distal femoral osteotomy (DDFO) for treating recurrent patellar dislocation (RPD) in the presence of increased femoral anteversion is one of the most commonly used surgical techniques in the current clinical practice. However, there are limited studies on the clinical outcomes of MPFL-R in combination with DDFO to treat RPD in the presence of increased femoral anteversion. Purpose To study the role of MPFL-R in combination with DDFO in the treatment of RPD in the presence of increased femoral anteversion. Methods A systematic review was performed according to the PRISMA guidelines by searching the Medline, Embase, Web of Science, and Cochrane Library databases through June 1, 2023. Studies of patients who received MPFL-R in combination with DDFO after presenting with RPD and increased femoral anteversion were included. Methodological quality was assessed using the MINORS (Methodological Index for Nonrandomized Studies) score. Each study’s basic characteristics, including characteristic information, radiological parameters, surgical techniques, patient-reported outcomes, and complications, were recorded and analyzed. Results A total of 6 studies with 231 patients (236 knees) were included. Sample sizes ranged from 12 to 162 patients, and the majority of the patients were female (range, 67-100%). The mean age and follow-up ranges were 18 to 24 years and 16 to 49 months, respectively. The mean femoral anteversion decreased significantly from 34° preoperatively to 12° postoperatively. In studies reporting preoperative and postoperative outcomes, significant improvements were found in the Lysholm score, Kujala score, International Knee Documentation Committee score, and visual analog scale for pain. Postoperative complications were reported in all studies, with an overall reported complication rate of 4.7%, but no redislocations occurred during the follow-up period. Conclusion For RPD with increased femoral anteversion, MPFL-R in combination with DDFO leads to a good clinical outcome and a low redislocation rate. However, there was no consensus among researchers on the indications for MPFL-R combined with DDFO in the treatment of RPD.

The N6-methyladenosine (m6A) modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs. Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder (MDD), a common neuropsychiatric disorder with an unclear aetiology. Here, we found that the levels of the circular RNA HECW2 (circHECW2) were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress (CUS) mouse model. Notably, the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS. Furthermore, we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP, leading to an increase in Gng4 expression via m6A modifications. Our findings provide functional insight into the correlation between circHECW2 and m6A methylation, suggesting that circHECW2 may represent a potential target for MDD treatment.

Summary: Background: The government-led community-based Chinese National Integrated Demonstration Areas for the Prevention and Control of Noncommunicable Diseases programme was launched in 2011, but no rigorous impact evaluation has been conducted to date. We aimed to evaluate the causal effects of this programme on behavioural risk factors. Methods: We used data from the latest five waves of the China Chronic Disease and Risk Factor Surveillance. The primary outcome is a behavioural risk score combining current smoking, passive smoking, drinking in last month, regular exercise, body mass index, and waist circumference. We applied the synthetic difference-in-differences method and constructed synthetic controls from the non-demonstration areas with the outcome. The average treatment effects on the treated were estimated for overall effect and by short- (1–2), medium- (3–4), and long-term (6–7 years) effects. Findings: We identified 26 demonstration areas (N = 72,193) and 100 non-demonstration areas (N = 275,397). Participants in the demonstration areas had higher education and income levels and different pre-implementation trends than non-demonstration areas. Using synthetic controls instead of non-demonstration areas reduced these pre-implementation differences. Compared to the synthetic controls, declines were observed in current smoking (−1.78% [−4.51%, 0.96%]), passive smoking (−8.09% [−14.27%, −1.90%]), and drinking in last month (−4.04% [−8.75%, 0.67%]) but not in the other factors. Behavioural risk score declined by 1.05 short-term (95% CI: −1.84, −0.26), 1.15 medium-term (95% CI: −2.08, −0.22), 2.82 long-term (95% CI: −4.79, −0.85), and 1.54 overall (95% CI: −2.51, −0.56). Interpretation: The programme improved behavioural risk scores, primarily through reductions in the prevalence of smoking and drinking, and the effect was long-lasting. Our findings provided empirical evidence for utilizing an integrated prevention and control strategy to fight against NCD in China and other countries facing similar challenges. Funding: The China National Key Research and Development Program (2018YFC1315304 and 2017YFC1310902); National Natural Science Foundation of China (81872721).

The bilateral teleoperation system is susceptible to model parameter uncertainty and unknown disturbances in both the master and slave manipulators, resulting in instability and inaccuracies in the force and position tracking performance. To address these issues, a novel nonlinear model reference adaptive impedance controller has been designed to achieve coordinated force and position synchronization of dual manipulators. The adaptive control laws, based on sliding mode functions, have been designed to compensate for the uncertainty of the manipulator model. Furthermore, an adaptive estimation law has been employed to appraise the unknown upper bound of external disturbances. This ensures that the closed-loop model parameters of the dual manipulator converge to the reference impedance model respectively. Simultaneously, it enables the position error between the reference model response and the end-effector task space position to asymptotically converge to zero. To verify the effectiveness of the proposed controller, simulations have been conducted on the MATLAB platform and experiments on a single degree of freedom teleoperation system have been performed. The results demonstrate that the controller exhibits strong robustness and has the capability of force-position tracking ability.

ObjectiveThe aim of the present study was to carry out a systematic research on bitterness quantification to provide a reference for scholars and pharmaceutical developers to carry out drug taste masking research. Significance: The bitterness of medications poses a significant concern for clinicians and patients. Scientifically measuring the intensity of drug bitterness is pivotal for enhancing drug palatability and broadening their clinical utility.MethodsThe current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to summarize the features, strengths, and applicability of quantitative bitterness assessment methods.ResultsIn our research, we systematically outlined the classification and key advancements in quantitative research methods for assessing drug bitterness, including in vivo quantification techniques such as traditional human taste panel methods, as well as in vitro quantification methods such as electronic tongue analysis. It focused on the quantitative methods and difficulties of bitterness of natural drugs with complex system characteristics and their difficulties in quantification, and proposes possible future research directions.ConclusionThe quantitative methods of bitterness were summarized, which laid an important foundation for the construction of a comprehensive bitterness quantification standard system and the formulation of accurate, efficient and rich taste masking strategies.

BackgroundSensorineural hearing loss (SNHL) children have difficulty living and limited movement due to impaired vestibular function and reduced balance ability.ObjectivesThe present study evaluated the effects of Latin dance training on the vestibular function and balance of SNHL children.MethodsThirty SNHL children with no difference in vestibular function and balance ability were randomly divided into two groups, the Latin dance training group (LTG, n = 15) and the control group (CONG, n = 15). Vestibular function, timed eyes-closed static (ECS) and functional reach test (FRT) were measured before and after the intervention, and a two-way repeated-measures analysis of variance was performed.ResultsAfter training, the vestibular function performance of LTG was higher than that of CONG (CONG: 16.425 ± 3.616 vs. LTG: 12.241 ± 2.610, p = 0.0411, ES = 1.3914), the left foot ECS performance of LTG was higher than that of CONG (CONG: 2.765 ± 0.872 vs. LTG: 4.688 ± 1.113, p = 0.0026, ES = 1.9857), the right foot ECS performance of LTG was higher than that of CONG (CONG: 3.113 ± 0.639 vs. LTG: 4.797 ± 1.071, p = 0.0137, ES = 2.01), the FRT performance of LTG was higher than that of CONG (CONG: 32.009 ± 6.134 vs. LTG: 43.797 ± 6.616, p = 0.0021, ES = 1.9135).ConclusionsAfter Latin dance training, SNHL children improved vestibular function and balance. The static balance ability of the left foot has been improved significantly than right foot.

Abstract Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN‐projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.

Abstract Climate change is creating a new era of infectious disease crises, further exacerbated by extreme weather. However, the relationship between extreme weather and infectious disease remain unclear. Here, we provide a new quantitative study on the impact of cold wave on COVID‐19 as an example. We found that during cold waves, extreme cold temperatures coupled with rapid aerosol transport accelerated COVID‐19 outbreaks. It directly increased the number of COVID‐19 cases in Beijing by 28.1% in the winter of year 2022. More urgently, cold temperatures led to a higher risk of death during infectious disease outbreaks, with a 7.07% increase in confirmed deaths and a 16.61% increase in excess mortality. Our findings emphasize the urgent need to promote a synergistic policy for responding to infectious diseases during cold wave disasters in order to minimize the risk of death among the elderly and those with underlying diseases.

ObjectiveThe study aimed to explore the risk factors for hyperuricemia (HUA) in the Naxi ethnic population residing in high-altitude areas of Yunnan, China, and assess the clinical value of the triglyceride/high-density lipoprotein cholesterol (TG/HDL-c) ratio as a diagnostic marker.MethodsIn this cross-sectional study, clinical data were collected from the health checkup population in the People's Hospital of Yulong Naxi Autonomous County, Yunnan Province, from January 2021 to January 2023. Participants were divided into quartiles based on the TG/HDL-c ratio (Q1, Q2, Q3, and Q4) for group analysis using chi-square tests, t-tests, and rank sum tests. Logistic regression analysis and linear regression models were employed to further investigate the correlation between the prevalence of hyperuricemia and TG/HDL-c ratio in this high-altitude Naxi population.ResultsA total of 714 participants from the health checkup population were included in the study, of whom 61.5% were male participants and 38.5% were female participants, and the average age was 41.21 ± 11.69 years. The mean uric acid level was 388.51 ± 99.24. After correcting for confounding factors, TG/HDL-c, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), red blood cells (RBCs), and hemoglobin (Hb) showed a positive correlation with blood uric acid. Further analysis involved categorizing the TG/HDL-c ratio from a continuous variable to a categorical variable using quartiles. The fully adjusted model showed results that were consistent with the trend observed in the continuous variable analysis when considering the TG/HDL-c ratio as a categorical variable. In addition, in all unadjusted and adjusted models, the serum uric acid (SUA) levels in the high TG/HDL-c ratio group were significantly higher than those in the low TG/HDL-c ratio group (trend p < 0.001). Further linear relationship analysis indicated that after adjusting for covariates, there was an approximate linear relationship between the TG/HDL-c and SUA levels, with a coefficient (β) of 5.421.ConclusionThe prevalence of hyperuricemia is greater in high-altitude areas of Yunnan, showing a nearly linear positive correlation with the TG/HDL-c ratio. Monitoring TG/HDL-c levels may benefit patients with hyperuricemia.

The drivers of changes in gut microbiota under arsenic exposure and the mechanism by which microbiota affect arsenic metabolism are still unclear. Here, C57BL/6 mice were exposed to 0, 5, or 10 ppm NaAsO2 in drinking water for 6 months. The results showed that arsenic exposure induced liver injury and increased the abundance of folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing microbiota. Statistical analysis and in vitro cultures showed that microbiota were altered to meet the demand for FA/VB12 by arsenic metabolism and to resist the toxicity of unmetabolized arsenic. However, at higher arsenic levels, changes of these microbiota were inconsistent. A 3D molecular simulation showed that arsenic bound to methionine synthase (MTR), which was confirmed by SEC-UV-DAD (1 μM recombinant human MTR was purified with 0 or 2 μM NaAsO2 at room temperature for 1 h) and fluorescence-labeled arsenic co-localization (primary hepatocytes were exposed to 0, 0.5, or 1 μM ReAsH-EDT2 for 24 h) in non-cellular and cellular systems. Mechanistically, the arsenic-MTR interaction in the liver interferes with the utilization of FA/VB12, which increases arsenic retention and thus results in a substantial increase in the abundance of butyrate-synthesizing microbiota compared to FA/VB12-synthesizing microbiota. By exposing C57BL/6J mice to 0 or 10 ppm NaAsO2 with or without FA (6 mg/L) and VB12 (50 μg/L) supplementation in their drinking water for 6 months, we constructed an FA/VB12 intervention mouse model and found that FA/VB12 supplementation blocked the disturbance of gut microbiota, restored MTR levels, promoted arsenic metabolism, and alleviated liver injury. We demonstrate that the change of gut microbiota is a response to arsenic metabolism, a process influenced by the arsenic-MTR interaction. This study provides new insights for understanding the relationship between gut microbiota and arsenic metabolism and present therapeutic targets for arseniasis.

Leaf functional traits (LFTs) are highly plastic and essential to plant resource acquisition and utilization. However, the collinearity of environmental factors and differences in the response of distinct functional types generate challenges in clarifying the contributions of environment variables to LFTs. This study selected 28 species from four forests in northern China with similar mean annual precipitation (MAP) to explore how other dissimilar environmental factors influence LFTs after controlling for the most influential factor. Specifically, we examined the effect of geographical (latitude, longitude, and altitude) and non-precipitation environmental factors (mean annual temperature (MAT), aridity index (AI), and soil pH) on leaf dry matter content (LDMC), and leaf carbon (LCC), nitrogen (LNC), and phosphorus (LPC) concentration, and pH. The collinearity of environmental factors on LFTs can be attributed to the regulation of moisture and temperature by geographical factors. Therefore, the remaining geo-environmental factors still played a significant role in LFT variation after excluding the most influential factor, which assist LFTs to maintain the original pattern of change across the environmental gradient. As latitude, longitude, and AI decreased, MAT increased, LCC and LPC decreased, LNC first increased, then decreased, and LDMC and leaf pH did not change significantly. The trends and intensity of LFTs variation varied between functional types. Significant differences in correlation were observed in LPC-to-LDMC and LPC-to-LNC across all regions for each species. Trait-trait relationships were inconsistent between life forms (herbs and woody plants) for leaf pH-to-nutrient concentration (C, N, P), LCC-to-LPC, and LCC-to-LDMC. Environmental variables were larger contributors to LFTs (especially LNC, LPC, and LDMC) variation than plant functional types (PFTs), while LCC and leaf pH were largely dependent of PFTs. These patterns result from plant adaptations to multiple variables, and a single environmental factor (even the core element that generated the collinearity of environmental factors such as MAP) in northern China cannot dominant geographic patterns among LFTs. This study sheds light on plant adaptation strategies to environmental change, deepening our understanding of ecosystem function and functional coordination.

Abstract cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

ObjectiveThis study investigated the link between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in American adults.MethodsInformation for 6495 participants from the National Health and Nutrition Examination Survey (NHANES) 2017–2020.03 was used for this cross-sectional study. The link between TG/HDL-C ratios and NAFLD and liver fibrosis was assessed by multiple linear regression before evaluating nonlinear correlations based on smoothed curve fitting models. Stratification analysis was then applied to confirm whether the dependent and independent variables displayed a stable association across populations.ResultsTG/HDL-C ratios were positively correlated with NAFLD, with higher ratios being linked to increased prevalence of NAFLD. After adjusting for potential confounders, the odds ratios (OR) for NAFLD patients in the fourth TG/HDL-C quartile were 3.61 (95% confidence interval [CI], 2.94–4.38) (P for trend < 0.001) in comparison with those in the first quartile after adjusting for clinical variables. However, no statistical significance was noted for the ratio for liver fibrosis after adjusting for potential confounders (P for trend = 0.07). A nonlinear correlation between TG/HDL-C ratios and NAFLD was observed based on smoothed curve fitting models. However, a nonlinear relationship between the ratios and liver fibrosis was not established. In subgroup analyses, there was an interaction between smoking status and TG/HDL-C ratio in relation to the prevalence of liver fibrosis (P for interaction < 0.001).ConclusionsAmong American adults, the TG/HDL-C ratio was noted to be nonlinearly positively associated with the prevalence of NAFLD; however, this relationship was not present in liver fibrosis.

Origami structures with morphing behaviours and unique mechanical properties are useful in aerospace deployable structures, soft robots and mechanical metamaterials. Curved-crease origami, as one of the variants in the origami family, has a curve that connects two vertices as a crease compared to the straight crease counterpart. This feature couples the crease folding and facet bending during the folding process, providing versatile design space of mechanical metamaterials with tunable stiffness, multi-stability properties and morphing behaviours. However, current design techniques are mostly for simple geometries with intuitive construction, the modelling technique focuses on using the conventional finite element method, and the intrinsically complex geometries make specimens difficult to manufacture, which further hinders the development of curved-crease origami structures. Thus, it is valuable to review the state-of-the-art in curved-crease origami. This paper presents a review on the design methodology, analytical methods, and applications of curved-crease origami over the years, discusses their strengths, identifies future challenges and provides an outlook for the future development of the curved-crease origami concept.

Steel structures in long-term service are difficult to avoid corrosion and can be reinforced by carbon fiber reinforced polymer (CFRP) bonding method. To investigate the corrosion effect on the bond behavior between CFRP and steel, a modified cohesive zone model was proposed and verified by experiment. Then, a series of random corrosion morphologies controlled by the size and the shape of corrosion pit were generated. Finally, by importing the random corrosion morphologies and the corresponding cohesive parameters distributions into the model, a parametric analysis was executed. Results showed that the ultimate load of CFRP-corroded steel bonding system was sensitive to the size of corrosion pit, while the stiffness had identical sensitivities to the pit size and pit shape. The ultimate load would reach the peak value when the average pit width Wp,avg was 1.0 mm and the average pit depth-to-width ratio (Dp/Wp)avg was between 0.12 and 0.14, whereas the stiffness would reach a high level when the Wp,avg was between 1.0 mm and 1.2 mm and the (Dp/Wp)avg was between 0.12 and 0.14. Moreover, the effective bond length would reach a high level when the Wp,avg was between 1.0 mm and 1.2 mm and the (Dp/Wp)avg was about 0.10.

Building energy flexibility plays a critical role in demand-side management for reducing utility costs for building owners and sustainable, reliable, and smart grids. Realizing building energy flexibility in tropical regions requires solar photovoltaics and energy storage systems. However, quantifying the energy flexibility of buildings utilizing such technologies in tropical regions has yet to be explored, and a robust control sequence is needed for this scenario. Hence, this work presents a case study to evaluate the building energy flexibility controls and operations of a net-zero energy office building in Singapore. The case study utilizes a data-driven energy flexibility quantification workflow and employs a novel data-driven model predictive control (MPC) framework based on the physically consistent neural network (PCNN) model to optimize the building energy flexibility. To the best of our knowledge, this is the first instance that PCNN is applied to a mathematical MPC setting, and the stability of the system is formally proved. Three scenarios are evaluated and compared: the default regulated flat tariff, a real-time pricing mechanism, and an on-site battery energy storage system (BESS). Our findings indicate that incorporating real-time pricing into the MPC framework could be more beneficial to leverage building energy flexibility for control decisions than the flat-rate approach. Moreover, adding BESS to the on-site PV generation improved the building self-sufficiency and the PV self-consumption by 17% and 20%, respectively. This integration also addresses model mismatch issues within the MPC framework, thus ensuring a more reliable local energy supply. Future research can leverage the proposed PCNN-MPC framework for different data-driven energy flexibility quantification types.

C21H18O4, monoclinic, P21/c (no. 14), a = 22.2457(10) Å, b = 5.0728(2) Å, c = 15.7045(7) Å, β = 110.012(2)°, V = 1665.22(13) Å3, Z = 4, Rgt (F) = 0.0434, wRref (F 2) = 0.1023, T = 100(2) K

This study aimed to develop an “environment-psychological” safety assessment model for urban villages. The objective was to create a comprehensive safety evaluation and identify key influencing factors. To start, establish a spatial environmental safety assessment system for urban villages, drawing on the six principles of Crime Prevention Through Environmental Design (CPTED) theory. Use Analytic Hierarchy Process and Bayesian network analysis for determining weights and scores. The research findings reveal that: 1) The safety of the spatial environment in urban villages is directly induced by factors such as “natural surveillance” and “image maintenance” while being indirectly impacted by factors like “territoriality” and “access control.” Notably, the effects of activity support and target hardening on spatial environmental safety are found to be insubstantial. 2) Z urban village in Xuzhou city has a level IV spatial environmental safety rating. Factors include line-of-sight transparency, environmental hygiene, and road layout. The proposed optimization measures include improving space layout, enhancing surveillance levels, and maintaining a favorable environment for crime prevention. This study aids decision-makers in establishing priority sequences for spatial planning during urban village renewal. The “Environment-Psychology” model enhances the explanatory power of environmental factors on psychological elements and can aid in spatial optimization strategies.

This paper considers setting different dips for different sub-faults to fit the actual rupture situation based on the fault rupture of the 2013 Lushan MS7.0 earthquake. Meanwhile, combined with the coseismic GNSS data of the Lushan earthquake, the source parameters and sliding distribution of the Lushan earthquake fault are inversed. Firstly, we use the gradient based optimizer (GBO) in nonlinear inversion to obtain the source parameters of this seismic fault. The inversion results indicate that the strike of the fault is 206.52°, the dip is 44.10°, the length is 21.92 km, and the depth is 12.79 km. To refine the sliding distribution of the seismic fault, the seismic fault is divided into 3 × 3 sub-faults. Then, we fix the central sub-fault dip of 44.10°; the dip of other sub-faults is obtained by iteration. After that, the model is further divided into a fault layer model composed of 23 × 19 sub fault slices, and using the Matlab fitting function is used to fit the dip of the 23 × 19 sub faults. Finally, the Lushan seismic fault plane is established as a shovel structure with steep upper and gentle lower, steep south and gentle north. The slip distribution inversion results indicate that the depth of the slip peak is 13 km, the corresponding maximum slip momentum is 0.67 m, the seismic moment is 1.10 × 1019 N·m and the corresponding moment magnitude is MW6.66. The results above are consistent with the research results of seismology.

The photovoltaic/thermal (PV/T) system is a promising option for countering energy shortages. To improve the performance of PV/T systems, compound parabolic concentrators (CPCs) and phase-change materials (PCMs) were jointly applied to construct a concentrating photovoltaic/thermal system integrated with phase-change materials (PV/T-CPCM). An open-air environment is used to analyze the effects of different parameters and the intermittent operation strategy on the system performance. The results indicate that the short-circuit current and open-circuit voltage are positively correlated with the solar irradiance, but the open-circuit voltage is negatively correlated with the temperature of the PV modules. When the solar irradiance is 500 W⋅m−2 and the temperature of the PV modules is 27.5 ºC, the short-circuit current and open-circuit voltage are 1.0 A and 44.5 V, respectively. Higher solar irradiance results in higher thermal power, whereas the thermal efficiency is under lower solar irradiance (136.2–167.1 W⋅m−2 is twice under higher solar irradiance (272.3–455.7 W⋅m−2). In addition, a higher mass flow rate corresponds to a better cooling effect and greater pump energy consumption. When the mass flow rate increases from 0.01 to 0.02 kg⋅s–1, the temperature difference between the inlet and outlet decreases by 1.8 ºC, and the primary energy-saving efficiency decreases by 0.53%. The intermittent operation of a water pump can reduce the energy consumption of the system, and the combination of liquid cooling with PCMs provides better thermal regulation and energy-saving effects under various conditions.

Abstract Background The timing of behavior and habitat use of nocturnal animals can be influenced by the lunar cycle in nature. The prevalence of artificial light at night (ALAN) has been recognized as a source of environmental pollution. The interaction between ALAN and the lunar cycle on bat behavior is important for understanding anthropogenic effects on bats. We utilized a decade (2012–2022) of acoustic monitoring data collected in North Carolina, United States, to investigate the relationship between bat activity, lunar cycle, and light pollution. We examined whether the amount of lunar illumination affected species-specific nightly activity and whether hourly bat activity patterns varied between nights with different moon phases. We further investigated if the relationship between bat activity and the lunar cycle might be altered by light pollution. Results We found that seven bat species showed activity variation across nights in relation to the amount of moon illumination when ALAN was absent. In general, bats were less active on full moon nights compared to new moon nights. Light pollution interacted with the bat–lunar relationship in five of the seven species, masking the effect of the lunar cycle. We identified delayed bat activity patterns on nights with a full or waxing moon in seven species, and light pollution altered that pattern in four species. Overall, ALAN was associated with decreased bat activity independent of lunar cycle effects. Conclusions Our study demonstrated that at a broad spatial scale, ALAN negatively affected many North American temperate bat species and altered their lunar chronobiology. As light pollution is spreading to historically dark areas and habitats, ALAN might couple with other threats, such as the white-nose syndrome or climate change, to cause cascading damage in the environment that depends on ecosystem services such as pest control provided by bats. We argue that further research and conservation actions are needed to mitigate the impact of light pollution.

Abstract Background Female fertility declines with increased maternal age, and this decline is even more rapid after the age of 35 years. Follicular fluid (FF) is a crucial microenvironment that plays a significant role in the development of oocytes, permits intercellular communication, and provides the oocytes with nutrition. Exosomes have emerged as being important cell communication mediators that are linked to age-related physiological and pathological conditions. However, the metabolomic profiling of FF derived exosomes from advanced age females are still lacking. Methods The individuals who were involved in this study were separated into two different groups: young age with a normal ovarian reserve and advanced age. The samples were analysed by using gas chromatography–time of flight mass spectrometry (GC–TOFMS) analysis. The altered metabolites were analysed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify the functions and pathways that were involved. Results Our data showed that metabolites in exosomes from FF were different between women of young age and women of advanced age. The set of 17 FF exosomal metabolites (P ≤ 0.05) may be biomarkers to differentiate between the two groups. Most of these differentially expressed metabolites in FF were closely involved in the regulation of oocyte number and hormone levels. Conclusions In this study, we identified differences in the metabolites of exosomes from FF between women of young age and women of advanced age. These different metabolites were tightly related to oocyte count and hormone levels. Importantly, these findings elucidate the metabolites of the FF exosomes and provide a better understanding of the nutritional profiles of the follicles with age.

Abstract Background Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. Methods Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. Results circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. Conclusions Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-B pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

Abstract Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp 3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp 3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp 3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.

Frequency stepping is a widely used technique for ultrahigh-resolution synthetic aperture radar (SAR). Although reducing the burden of hardware, this technique increases the complexity of imaging algorithms due to the intersubband time offsets and intersubband errors of delay, amplitude, and phase. To address the above problems, an improved ultrahigh-resolution stepped-frequency spaceborne SAR imaging algorithm is proposed in this article. By generating subband images individually, performing intersubband error estimation based on primary points, and then synthesizing the subband images in the imaging domain, the proposed algorithm effectively avoids the problem of time offsets and significantly improves intersubband error compensation accuracy benefiting from the high SNR in the imaging domain. Besides, considering the characteristics of nonideal factors in frequency-stepped SAR, a series of error compensation methods aiming at stop-and-go approximation, ionospheric error, and tropospheric delay are integrated to the proposed algorithm. The effectiveness of the proposed algorithms is verified via computer simulations, and real data experiments are also conducted based on both an X-band spaceborne SAR system, Taijing 4-01, and a Ka-band spaceborne SAR system, Luojia 2-01.

Abstract Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P

Introduction Our objective was to examine the factors associated with the serum angiopoietin-2/angiopoietin-1 (Angpt-2/Angpt-1) ratio in peritoneal dialysis (PD) patients and to investigate the association between Angpt-2/Angpt-1 ratio and cardiovascular and all-cause mortality.Methods Patients on PD who were prevalent between January 2014 and April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters, serum angiopoietin-2 and angiopoietin-1 levels. Patients were dichotomized into two groups according to a median of Angpt-2/Angpt-1 ratio and followed up prospectively until the end of the study.Results A total of 325 patients were enrolled, including 168 males (51.7%) with a mean age of 56.9 ± 14.2 years and a median PD duration of 32.4 (9.8-55.9) months. Multiple linear regression showed pulse pressure (β = 0.206, p .05).Conclusions High Angpt-2/Angpt-1 ratio is an independent risk factor for cardiovascular and all-cause mortality in PD patients.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.