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Hydraulic performance and operational stability of submersible drainage pumps can be affected by cavitation and erosion when used for draining water from buildings. A parametric study is essential to improve the suction performance and accurately identify the cavitation and erosion phenomena in the pump, providing a technical reference for monitoring its optimal operation. Therefore, the main objective of this research is to develop an energy-saving, high-efficiency submersible pump capable of emergency response. In this paper, the Reynolds-average Navier-Stokes (RANS) equations were applied to the steady calculation of the submersible pump, which was discretized by the finite volume method. The Reyleigh-Plesset cavitation model was considered for interphase mass transfer to predict and find the cavitation characteristics. Additionally, the discrete phase model (DPM) was adopted as an Eulerian-Eulerian approach combined with Grant and Tabakoff's erosion model to capture the erosion effects in the pump numerically. A test pump was installed, and an experiment was conducted to assess hydraulic performance, validated with computational data. Improving the impeller or casing shape can increase NPSH3 % by at least 3.80 %, with a potential improvement of 4.083 % when only the impeller shape is changed. Erosion rate density increases with particle inflow rate, but model differences decrease as the flow rate increases. Modifying the impeller and casing shapes can reduce the average erosion rate density by at least 25 %. Average efficiency improvements of 4–5 % can be achieved by optimizing the casing shape, though practical implementation is challenging. Optimizing the pump's flow path is essential for improving hydraulic performance and reducing erosion and cavitation.

Abstract Abnormalities of carbohydrate antigen 19 − 9 (CA19-9) are common in patients with type 2 diabetes mellitus (T2DM), and in some patients, CA19-9 returns to normal level after glycemic control. The aim of this study was to investigate the factors associated with CA19-9 levels in patients with T2DM and the associated influences on the degree of reduction of CA19-9 levels after antidiabetic therapy (AT). This study was an observational cross-sectional study. A total of 213 patients with T2DM were enrolled in this study, of whom 105 with abnormal CA19-9 and 108 with normal CA19-9. Socio-demographic information, complete blood counts, biochemical indicators, thyroid function indicators, and CA19-9 level were collected separately for each subject. Levels of glycosylated hemoglobin, type A1C (HbA1c), fasting blood glucose (FBG) were significantly higher in T2DM patients with abnormal CA19-9 compared to patients with normal CA19-9 (both FDR

Abstract The COVID-19 event triggered global attention which broke out at the end of 2019. To investigate the impact of the COVID-19 pandemic prevention and control actions on the chemical composition, size distribution, and mixing state of individual particles, real-time individual particles in the urban atmosphere of the Northern China were analyzed using single particle aerosol mass spectrometry (SPAMS) during January 16 to February 4, 2020. The results showed that the concentrations of PM2.5, NOx, and CO were lower during DP (during the pandemic) than those during BP (before the pandemic), while O3 concentration increased by about 40.9% during DP due to a lower concentration of NO2 restraining the decomposition of O3 via the reaction of NO with O3. The number count of carbonaceous particles during DP decreased by 20.2% compared to that during BP due to the sharp reduction of factory production and vehicular transportation during DP. Dust particles during DP exhibited weaker 23Na+, 56Fe+, and 79PO3− signals than those during BP, suggesting that dust particles during DP were mostly derived from mineral dust rather than industrial sources. The total particles during DP peaked at a larger size than those during BP, due to the higher fraction of secondary inorganic ions through the enhanced heterogeneous aqueous oxidation. The unscaled size distribution of total particles peaked at 0.50 µm during BP and at 0.66–0.70 µm during DP, suggesting that particles remained for a long time in the atmosphere and went through a strong aging process during DP. The single particles during DP were more aged than those during BP, owing to the stronger atmospheric oxidizing capacity during DP.

Objective Leg problems including lameness and tibial dyschondroplasia (TD) are one of the most important factors affecting health and animal welfare in meat-type poultry, which are considerably impacted by dietary vitamin regimens. The present study was conducted to investigate the effects of dietary vitamin levels on growth performance and tibia quality in 14-d-old meat ducks. Methods One-d-old Cherry Valley meat-type male ducks were allocated to two vitamin regimens for 14 d, which was formulated according to the recommendation of the National Research Council (NRC, 1994) or China Agricultural Industry Standards (NY/T 2122-2012). Each group included 8 replicates with 16 birds per replicate. Results There was no significant difference in the growth performance of ducks, whereas dietary NY/T vitamin supplementation decreased leg abnormalities as compared to the NRC group, along with similar tibia length, perimeter, and the relative weight of tibia. The tibia from the birds that received the NY/T vitamin diet exhibited markedly higher (p 0.05). Conclusion NY/T vitamin diet improved tibia quality and subsequently decreased leg abnormalities in 14-d-old ducks, which was probably linked with the promoted bone formation.

Whereas some studies suggest that ironic praise necessitates a longer processing time than ironic criticism, others posit that the two are processed at comparable speeds. We hypothesize that the presence of an echoic antecedent within the preceding context may at least partially account for these conflicting findings. To investigate this matter, we analyzed reading times and accuracy stemming from two types of contexts: echoic and non-echoic. Our results demonstrate that ironic criticism was judged to be more ironic in both echoic and non-echoic contexts, while ironic praise was rated as more ironic in an echoic context than in a non-echoic context. Additionally, echoing contexts facilitate the comprehension of ironic criticism, but cause ironic praise to be processed more slowly. There was also an observed asymmetry between the two forms of irony. Ironic criticism demonstrated high accuracy and was rated as more ironic than ironic praise. Furthermore, ironic criticism was read faster in an echoic context, whereas performance was similar in a non-echoic context for both types. These findings suggest that echoing context affects ironic criticism and ironic praise differently, implying that distinct mechanisms may be at work in understanding irony in echoic and non-echoic contexts.

Abstract Purpose Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway. Methods The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6’s role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1’s pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference’s inhibitory effect on CC proliferation in vivo. Results Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments. Conclusion Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment.

Abstract Despite the importance of radiation therapy as a nonsurgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern because of poor patient response and outcomes. Therefore, it is crucial to identify novel targets to increase the effectiveness of radiotherapy and investigate the mechanisms underlying radioresistance. Previously, we demonstrated that Spindlin 1 (SPIN1) was related to tumour initiation and progression. In this study, we found that SPIN1 expression was higher in NSCLC tissues and cell lines than in the corresponding controls. SPIN1 overexpression in NSCLC patients was closely correlated with disease progression and poor prognosis. Functionally, SPIN1 depletion inhibited cell proliferation, decreased the percentage of cells in the G2/M phase and suppressed cell migration and invasion. Moreover, SPIN1 knockdown decreased the clonogenic capacity, impaired double-strand break (DSB) repair and increased NSCLC radiosensitivity. Mechanistically, forkhead box M1 (FOXM1) was identified as a key downstream effector of SPIN1 in NSCLC cells. Furthermore, SPIN1 was found to facilitate MDM2-mediated FOXO3a ubiquitination and degradation, leading to FOXM1 upregulation. Moreover, restoration of FOXM1 expression markedly abolished the inhibitory effects and increased radiosensitivity induced by SPIN1 depletion. These results indicate that the SPIN1-MDM2-FOXO3a/FOXM1 signalling axis is essential for NSCLC progression and radioresistance and could serve as a therapeutic target for increasing radiotherapy efficacy.

Abstract Mobile phone addiction has become a widespread phenomenon in Chinese society, attracting significant social attention. However, there is still limited understanding of complexities and relationships concerning anxiety, depression, self-esteem, and mobile phone addiction (MPA) among college students. To better understand the relationships among depression, anxiety, self-esteem, and mobile phone addiction, the aim of this study was to explore these relationships, analyze the factors influencing mobile phone addiction, and examine the mediating effects of anxiety and self-esteem on the relationship between depression and mobile phone addiction. Data from 2023 were collected, and the SDS depression scale, SAS anxiety scale, mobile phone addiction scale, and Robert self-esteem scale were employed. Pearson correlation analysis and structural equation modeling revealed significant associations between depression, anxiety, self-esteem, and mobile phone addiction. Further analysis indicated that anxiety mediated the relationship between depression and mobile phone addiction, meanwhile, self-esteem mediated the relationship between depression and mobile phone addiction. Self-esteem also mediated the relationship between anxiety and mobile phone addiction. Additionally, anxiety and self-esteem played sequential mediating roles in mobile phone addiction. These findings contribute to a better understanding of the mechanisms underlying the relationship between depression and mobile phone addiction. The discussion provides practical and effective recommendations for the prevention and intervention of mobile phone addiction among college students.

Atherosclerosis (AS) is a chronic inflammatory disease that primarily affects large and medium-sized arteries and is one of the leading causes of death worldwide. This article reviews the multifaceted role of mitochondrial DNA (mtDNA) in AS, including its structure, function, release, and relationship with inflammation. Damage and release of mtDNA are considered central drivers in the development of AS, as they participate in the progression of AS by activating inflammatory pathways and affecting lipid metabolism. Therefore, therapeutic strategies targeting mtDNA and its downstream effects may provide new avenues to address this global health challenge.

BackgroundAfter initial treatment, levothyroxine (LT4) administration is necessary for thyroid cancer patients to achieve target thyroid-stimulating hormone (TSH) levels. However, the clinical efficacy of weight-based LT4 dosing has been suboptimal, highlighting the need to identify factors influencing the attainment of desired TSH levels and guide personalized treatment.MethodsWe constructed a retrospective cohort comprising 215 patients diagnosed with thyroid cancer. The identification of factors influencing the attainment of expected TSH levels was accomplished through univariate and multivariate logistic regression analyses. Subsequently, we developed a nomogram based on these prognostic factors and performed internal validation using the bootstrap resampling method.ResultsUnivariate and multivariate logistic regression analyses were conducted to analyze the clinical and demographic parameters. A nomogram was constructed using bootstrap resampling to predict the risk of TSH suppression failure, which was validated. The nomogram demonstrated moderate discrimination in estimating the risk of TSH suppression failure, with a Hosmer-Lemeshow test p-value of 0.393 and a bootstrapped calibrated C-index of 0.757 (95% CI 0.687-0.814). The calibration curve indicated good consistency of the model, and decision curve analysis suggested that the nomogram had clinical utility.ConclusionGender, preoperative serum free thyroxine (FT4) levels, T stage, and body mass index exhibit independent associations with the expected level of TSH. The established nomogram effectively predicts the risk of TSH suppression failure. Further research is warranted to investigate how these factors can be utilized in developing a personalized LT4 dosage calculator.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

The treatment of COVID-19 in the post-transplant individuals is challenging, primarily due to the drug-drug interaction between nirmatrelvir/ritonavir and tacrolimus. Deuremidevir hydrobromide tablets (VV116) is an orally small molecule agents target SARS-CoV-2 RdRp and inhibits viral replication. It may have a low likelihood of drug-drug interactions and has a potential to provide new treatment option. We described three cases of renal transplant patients with concomitant impaired renal function who developed COVID-19 pneumonia and were treated with VV116. Despite varying degrees of drug accumulation, these patients achieved rapid viral clearance and showed prompt improvement in pneumonia symptoms. Notably, tacrolimus blood concentrations remained within the therapeutic range throughout treatment, and no clinically significant adverse events were observed despite the drug accumulation.

Hyperspectral images are rich in spectral and spatial information, providing a detailed and comprehensive description of objects, which makes hyperspectral image analysis technology essential in intelligent agriculture. With various corn seed varieties exhibiting significant internal structural differences, accurate classification is crucial for planting, monitoring, and consumption. However, due to the large volume and complex features of hyperspectral corn image data, existing methods often fall short in feature extraction and utilization, leading to low classification accuracy. To address these issues, this paper proposes a spectral-spatial attention transformer network (SSATNet) for hyperspectral corn image classification. Specifically, SSATNet utilizes 3D and 2D convolutions to effectively extract local spatial, spectral, and textural features from the data while incorporating spectral and spatial morphological structures to understand the internal structure of the data better. Additionally, a transformer encoder with cross-attention extracts and refines feature information from a global perspective. Finally, a classifier generates the prediction results. Compared to existing state-of-the-art classification methods, our model performs better on the hyperspectral corn image dataset, demonstrating its effectiveness.

PurposeBody Mass Index (BMI) is an important indicator for assessing obesity and related health risks. With the rapid socio-economic development and changes in lifestyle, abnormal BMI (such as underweight, overweight, and obesity) has become an increasingly serious public health issue. This study aims to explore the impact of exercise frequency on BMI among Chinese adults aged 19 to 59, and to analyze the role of dietary behaviors in regulating BMI, providing a basis for BMI intervention strategies.MethodThe study employs a multi-stage sampling method across 23 provinces, provincial capitals, and four municipalities in China, randomly selecting 120 cities from each region. Online surveys were conducted using Wenjuanxing by trained surveyors.ResultA total of 8,611 individuals participated in the survey. Among them, 1,066 (12.38%) had a BMI

This research explores the link between hydropneumatic energy storage capacity and the efficiency and flexibility of hybrid energy systems in water-energy solutions. A new methodology is introduced, featuring mathematical models, experimental data collection, and hydraulic simulations using 1D and 2D CFD models for hydropneumatics modeling. A promised energy storage efficiency of around 30–50 % was obtained on a small lab scale. The optimization of hybrid systems through Solver and Python algorithms with various objective functions enables optimal design choices tailored to specific needs such as drinking water supply, irrigation, or industrial processes. Hydropneumatic vessels emerge as an effective storage solution, combining pumped storage and hydropower in one circuit. When integrated with renewable sources, such as solar (PV) and wind energy, they offer a flexible, long-lasting energy management system, applicable across different water-energy sectors to support Sustainable Development Goals. A case study with 4.8 Mm³/year water allocation, producing 1000 MWh of hydropower and 13500 MWh of solar energy, achieved 100 % water reliability and a 25-year cash flow of 2.5 million euros.

Serine protease inhibitors (Serpins) are a protein superfamily of protease inhibitors that are thought to play a role in the regulation of inflammation, immunity, tumorigenesis, coagulation, blood pressure and cancer metastasis. Serpins is enriched in the skin and play a vital role in modulating the epidermal barrier and maintaining skin homeostasis. Psoriasis is a chronic inflammatory immune-mediated skin disease. At present, most serpins focus on the pathogenesis of psoriasis vulgaris. Only a small number, such as the mutation of SerpinA1/A3/B3, are involved in the pathogenesis of GPP. SerpinA12 and SerpinG1 are significantly elevated in the serum of patients with psoriatic arthritis, but their specific mechanism of action in psoriatic arthritis has not been reported. Some Serpins, including SerpinA12, SerpinB2/B3/B7, play multiple roles in skin barrier function and pathogenesis of psoriasis. The decrease in the expression of SerpinA12, SerpinB7 deficiency and increase in expression of SerpinB3/4 in the skin can promote inflammation and poor differentiation of keratinocyte, with damaged skin barrier. Pso p27, derived from SerpinB3/B4, is an autoantigen that can enhance immune response in psoriasis. SerpinB2 plays a role in maintaining epidermal barrier integrity and inhibiting keratinocyte proliferation. Here we briefly introduce the structure, functional characteristics, expression and distribution of serpins in skin and focus on the regulation of serpins in the epidermal barrier function and the pathogenic role of serpins in psoriasis.

The fluidisation of spherocylindrical particles is often involved in the fields of biomass combustion, drug delivery and food drying. By spherocylindrical particles, we mean elongated spherical particles like non-spherical capsule pills and pulverised biomass fuels. Mastering the fluidisation state of spherocylindrical particles can improve the related industrial processes. In this paper, a coupled CFD–DEM method is used and the reliability of the model in this paper is verified with the help of high-speed photography experiments. Subsequently, the fluidisation characteristics of spherocylindrical particles in a spouted bed were investigated under different operating conditions and compared with the simulation results of spherical particles. The results show that the gas velocity influences the average bed height, axial velocity, volume fraction, orientation angle, and mixing mass of the particles. There are also significant differences in the fluidisation characteristics of particles at different bed heights. The particles in the higher bed region are more dispersed, the gas–solid mixing is more intense, and the gas velocity has a strong influence on the volume fraction/axial velocity of the spherocylindrical particles in the higher bed. In addition, this work also found significant differences in the fluidisation characteristics of different shaped particles.

Autoimmune thyroiditis (AIT), also known as Hashimoto’s thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.

Sewage pumps are widely utilized in various applications, including municipal wastewater treatment plants, industrial processes, and residential sewage systems. These pumps are specifically designed to handle the transportation of mixtures consisting of solid and liquid components, commonly observed as two-phase flow. In this study, semi-open sewage pumps with varying clearance sizes have been examined through adjustment of the geometrical model. Multi-factor analysis of variance is employed to investigate the combined influence of different two-phase flow conditions and tip clearance sizes on the performance of sewage pumps. The results show that the performance of the pump decreases significantly as the clearance size increases. Also, the sensitivity of pump efficiency to variations in tip clearance size is contingent upon the flow rate. Under part-load conditions, both particle concentration and clearance size exhibit a notable effect on efficiency. The two-phase flow will greatly enhance the intensity of the unsteady flow near the inlet and outlet of the semi-open impeller, which is the main reason for the performance degradation of the sewage pump. The findings of this research provide valuable insights for enhancing the hydraulic performance and operational stability of semi-open sewage pumps operating under two-phase flow conditions.

A robust comprehensive energy dissipation model is developed to investigate the rapid filling process of a T-shaped bifurcated pipeline with entrapped air pocket, while an experimental system is designed to validate the numerical model. In this work, a self-adapting heat transfer model is proposed to describe the energy exchange during transient event, fully considering the heat transfer of entrapped air pocket and hydraulic losses caused by steady friction and unsteady friction in the section of the filling water column. Importantly, the related heat transfer coefficient is variable and determined by mechanism formula of media characteristics, which is obviously different from the constant heat transfer coefficient in conventional model relying on the trial-and-error method and experimental data. Moreover, the second-order Godunov-type scheme is introduced to solve the governing equations of filling water column, while a virtual plug approach is proposed to track the air–water interface. The resulting predictions are compared to those obtained via a conventional empirical polytropic model and constant coefficient heat transfer model, and to experimental data. The proposed model accurately reproduces the experimental pressure oscillations. The results display that when an air pocket content exceeds a certain threshold (>1.7%), the comprehensive model using forced convection can reproduce the pressure fluctuations. When the air content is lower (

Background Prognostic factors-based nomograms have been utilised to detect the likelihood of the specific cancer events. We have focused on the roles of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the prognosis of BC patients. This study was designed to establish nomograms based on the integration of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the disease-free survival (DFS) and overall survival (OS) of breast cancer (BC) patients.Methods Demographic and clinical data were obtained from BC patients admitted to our hospital between September 2015 and August 2016. Univariate and multivariate Cox regression analyses were utilised to analyse the risk factors of recurrence and mortality. The nomograms for predicting the DFS and OS were established using the screened risk factors. Stratified analysis was performed with the cut-off value of exp (pi) of 4.0-fold in DFS and OS, respectively.Results Multivariate Cox regression analysis indicated that ALDH, p-AKT and pathological stage III were independent risk factors for the recurrence among BC patients. ALDH1, p-AKT, pathological stage III and ER-/PR-/HER2- were independent risk factors for the mortality among BC patients. The established nomograms based on these factors were effective for predicting the DFS and OS with good agreement to the calibration curve and acceptable area under the receiver operating characteristic (ROC) curve. Finally, stratified analyses showed patients with a low pi showed significant decrease in the DFS and OS compared with those of high risk.Conclusion We established nomograms for predicting the DFS and OS of BC patients based on ALDH1, p-AKT and pathological stages. The ER-/PR-/HER2- may be utilised to predict the OS rather than DFS in the BC patients.

The diagnostic criteria for preeclampsia do not accurately reflect the pathophysiological characteristics of patients with preeclampsia. Conventional biomarkers and diagnostic approaches have proven insufficient to fully comprehend the intricacies of preeclampsia. This study aimed to screen differentially abundant metabolites as candidate biomarkers for preeclampsia. A propensity score matching method was used to perform a 1:1 match between preeclampsia patients (n = 70) and healthy control individuals (n = 70). Based on univariate and multivariate statistical analysis methods, the different characteristic metabolites were screened and identified. Least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently used to further screen for differentially abundant metabolites. A receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of the metabolites. A total of 1,630 metabolites were identified and quantified in maternal serum samples. Fifty-three metabolites were significantly increased, and two were significantly decreased in preeclampsia patients. The area under the curve (AUC) of the model composed of isobutyryl-L-carnitine and acetyl-leucine was 0.878, and the sensitivity and specificity in detecting preeclampsia were 81.4% and 87.1%, respectively. There are significant differences in metabolism between preeclampsia patients and healthy pregnant women, and a range of novel biomarkers have been identified. These findings lay the foundation for the use of metabolomic biomarkers for the diagnosis of preeclampsia.

The traditional one-dimensional (1D) model often fails to accurately predict the dynamic pressure response of large offline air pockets during transients, due to a lack of comprehensive understanding of the underlying mechanisms of transient interaction with offline air pockets. This study investigated dynamic behavior and energy dissipation of offline air pockets through experiments and numerical models. Experimental pressure responses were predicted using a 1D-3D coupling model, which presented superior performance compared to traditional 1D model. The 1D-3D coupling model was further utilized to investigate the air-water interface, internal energy and turbulence distribution of offline air pockets. The results reveal that the stability of the air-water interface depends on the decelerating distance of the jet in offline tube, explaining the instability phenomenon with lower water levels observed in experimental snapshots. The internal energy pattern suggests different energy dissipation mechanisms compared to the inline air pockets. The distribution of turbulence intensity and effective thermal conductivity indicates significant additional energy dissipation at the inlet and outlet of offline neck. By incorporating a minor head loss term for offline neck into traditional 1D model, the pressure response aligns well with the results obtained from 1D-3D coupling model under different flow rates and air volumes.

Transient flow frequently occurs in water delivery systems, including various flow regimes such as water hammer, free surface flow, and slug flow. Current models often oversimplify these phenomena by simulating single-phase flow or using simplistic one-dimensional assumptions for the gas-water interface, neglecting interface instability. Although two-fluid models can address some of these issues, they cannot simulate open channel flow and have not yet been applied to transient flow scenarios. To date, no single model has been able to simultaneously simulate all these flow regimes while overcoming these limitations. To address this gap, the two-fluid model is enhanced in this paper. For water hammer simulation, a gas volume fraction of zero is assumed, and a TVB unsteady friction model is introduced to enhance numerical accuracy. For open channel flow, a variable wave speed equation and a new state equation are presented. Despite the different state equations required for various flow regimes, a Roe-type scheme is introduced to solve the two-fluid model. This approach accurately simulates water hammer, free surface flow (including open channel flow and stratified flow), and slug flow. An experimental pipeline system is designed to validate the proposed model's ability to simulate water hammer. Additionally, several cases are used to verify the model's capability in simulating open channel flow, stratified flow, and slug flow. The model accurately predicts the occurrence of slug flow, consistent with experimental flow pattern maps, and effectively simulates the evolution of slug flow, closely matching the measured gas-water interface. The effects of gas volume fraction, pipe length, and pipe slope on slug flow are systematically discussed. Results indicate that smaller initial gas volume fractions, longer pipe lengths, and upward pipe slopes increase the likelihood of slug flow generation within the pipeline, which should be minimized during design.Abbreviations: TVB: Trikha-Vardy-Brown model; Cr: Courant number

In this paper, a discrete air model (DAM) is developed to capture the discontinuous characteristics of air at different locations during the rapid filling process in long-range, large-scale water pipeline. By introducing the continuity and momentum equations of air and combining them with the water control equation and the interface continuity equation, an improved model based on the uniform air is derived. The accuracy of the model is verified by comparing it with experimental data and the results of the original uniform air model (UAM). Subsequently, a long-range, large-scale pipeline was considered to investigate the dynamic properties of air in large systems, which had not been covered in previous studies. Additionally, the influence of air dynamic characteristics on initial air volume affected by different air lengths and various pipe diameters in large systems – is further studied. Results show that an increased pipe diameter expands the contact area of the air–water interface, often resulting in the UAM underestimating the maximum peak pressure. The propagation process of transient waves in air is divided into three stages: propagation stage with multiple variation, maximum value stage with interface propulsive, and stability stage with several fluctuations, which corresponds to the pressure fluctuation curve. This explains the occurrence of small fluctuations and peaks in the curve. Therefore, the peak pressure simulated by the proposed DAM offers a better understanding of wave behaviours.

Abstract The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2’s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer’s opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

Abstract Background Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it’s unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. Methods To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. Results In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. Conclusion In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Abstract Background The plant-specific YABBY transcription factor family plays important roles in plant growth and development, particularly leaf growth, floral organ formation, and secondary metabolite synthesis. Results Here, we identified a total of 13 OfYABBY genes from the Osmanthus fragrans genome. These 13 OfYABBY genes were divided into five subfamilies through phylogenetic analysis, and genes in the same subfamily showed similar gene structures and conserved protein motifs. Gene duplication promoted the expansion of the OfYABBY family in O. fragrans. Tissue-specific expression analysis showed that the OfYABBY family was mainly expressed in O. fragrans leaves and floral organs. To better understand the role of OfYABBY genes in plant growth and development, OfYABBY12 was selected for heterologous stable overexpression in tobacco, and OfYABBY12-overexpressing tobacco leaves released significantly fewer volatile organic compounds than wild-type tobacco leaves. Overexpression of OfYABBY12 led to the downregulation of NtCCD1/4 and decreased β-ionone biosynthesis. Correspondingly, a dual-luciferase assay showed that OfYABBY12 negatively regulated the expression of OfCCD4, which promotes β-ionone synthesis. Furthermore, tobacco leaves overexpressing OfYABBY12 were curled and wrinkled and had significantly reduced leaf thickness and leaf inclusions and significantly extended flower pistils (styles). Conclusion Overall, the results suggest that the OfYABBY gene family may influence the biosynthesis of the floral scent (especially β-ionone) in O. fragrans and may regulate leaf morphogenesis and lateral organs.

Photodynamic therapy is an “old” strategy for cancer therapy featuring clinical safety and rapid working, but suitable photosensitizers for colorectal cancer therapy remain lacking. This study synthesized a novel photosensitizer termed Ce6-GFFY based on a self-assembling peptide GFFY and a photo-responsive molecule chlorin e6 (Ce6). Ce6-GFFY forms macroparticles with a diameter of ∼160 nm and possesses a half-life of 10 h, as well as an ideal tumor-targeting ability in mouse models. Ce6-GFFY effectively penetrates cells and generates numerous reactive oxygen species upon 660 nm laser irradiation. The reactive oxygen species promotes the accumulation of cytotoxic T cells and decrease of myeloid-derived suppressor cells in the tumor microenvironment through immunogenic cell death, thus prohibiting the growth of both primary and metastatic tumors after once treatment. This study not only provides a strategy for photosensitizer development but also confirms a promising application of Ce6-GFFY for colorectal cancer therapy.

BackgroundThyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy.MethodsUsing data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings.ResultsIn UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10–1.19; P

Fruit color is an important qualitative trait that greatly influences the marketability of peppers. Fruit color can be divided into two categories. Green fruit color denotes commercial maturity, whereas ripe fruit indicates physiological maturity. Herein, segregation populations were created using the ‘D24’ with pale green in the green fruit stage, orange in the mature fruit stage, and ‘D47’ with green in the green fruit stage and red in the mature fruit stage. BSA-seq and genetic linkage map analysis revealed green fruit color was linked to (gyqtl1.1) on Chr1 and (gyqtl10.1) on Chr10, while mature fruit color was linked to Chr6. Using functional annotation, sequence, and expression analysis, we speculate that an SNP mutation in the CapGLK2 gene at the gyqtl10.1 interval could initiate premature termination of translation, thus yielding green to pale green fruits in D47. Conversely, the orange color in mature D24 fruits is due to the Indel-mediated premature termination of translation of the CapCCS gene. Our research offers a theoretical foundation for choosing different varieties of pepper fruit based on their color.

Objective: This study aimed to clarify the mechanism by which Krüppel-like factor 12 (KLF12) affects progesterone sensitivity in endometrial cancer (EC) through the progesterone receptor PGR signaling pathway. Methods: The relationship of KLF12 with PGR in EC patients was examined by immunohistochemistry, and the expression of KLF12 and PGR in EC cell lines was detected by real-time PCR and western blotting. Cell proliferation assay, plate clone formation, cell apoptosis assay, and cell cycle analysis were conducted to determine the impact of KLF12 intervention on progesterone therapy. CUT&Tag analysis and the dual-luciferase reporter experiment were used to determine the underlying regulatory effect of KLF12 on the PGR DNA sequence. A subcutaneous xenograft nude mouse model was established to validate the in vivo effect of KLF12 on progesterone sensitivity via PGR expression modulation. Results: KLF12 demonstrated decreased progesterone sensitivity and a negative correlation with PGR expression in EC tissues. Progesterone sensitivity was increased by KLF12 deficiency through PGR overexpression, a result that could be significantly reversed by PGR downregulation. PGR was identified as a target gene of KLF12, which could directly bind to the PGR promotor region and inhibit its expression. Conclusion: This study is the first to investigate the effect of KLF12 expression on EC cell resistance to progesterone. Our results offer important mechanistic insight into the direct regulation of the PGR promoter region, demonstrating that KLF12 expression strongly suppressed the PGR signaling pathway and, as a result, reduced progesterone sensitivity in EC patients.

The differentiation of vascular endothelial cells and the formation of new blood vessels are inseparable from the energy supply and regulation of metabolism. The budding of blood vessels is a starting point of glycolysis pathway in angiogenesis. Phosphofructokinase-2/fructose 2,6-biophosphatase 3 (PFKFB3), a key rate-limiting enzyme in glycolysis, exhibits strong kinase activity. Inhibition of PFKFB3 can reduce the rate of glycolysis, thereby inhibiting the budding of blood vessels, resulting in inhibition of pathological angiogenesis. In this review, the role of PFKFB3 in the angiogenesis of inflammatory diseases was summarized, and the endothelial inflammatory diseases associated with PFKFB3 were reviewed.

Abstract Endocrine‐resistant ER+HER2– breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine‐resistant BC remain elusive. Here, analysis of the RNA‐sequencing data from ER+HER2– BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine‐resistant BC cells, not immune cells. Indeed, compared with endocrine‐sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS‐STING pathway is attenuated in endocrine‐resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS–STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2– BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine‐resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine‐resistant BC.

A lack of access to handwashing facilities is a significant risk factor for lower respiratory infections(LRIs). However, no studies have reported epidemiologic changes in the burden of LRIs attributed to the lack of access to handwashing facilities. We conducted an integrated assessment of the burden of LRIs attributable to the lack of handwashing facilities from 1990 to 2019 using data from the Global Burden of Disease Study 2019. In 2019, 270,000 deaths were attributed to LRIs due to a lack of access to handwashing facilities, with DALYs reaching 14.02 million. The age-standardized mortality rate (ASMR) of LRIs caused by a lack of access to handwashing facilities was approximately 3.74, while the age-standardized DALY rate (ASDR) was reported to be 203.55 in 2019. Over the past 30 years, the burden of LRIs attributed to the lack of access to handwashing facilities has shown a global decline. In 2019, this burden was most pronounced in infants under 1 year of age and in those older than 95 years, reflecting the highest DALY (5591.83) and mortality rates (79.43), respectively. The burden of LRIs caused by the lack of access to handwashing facilities was found to be more severe in males and significantly more pronounced in regions with a low sociodemographic index (SDI), such as the Sahara African region. The development of targeted strategies to address the inadequate and unequal distribution of handwashing facilities holds important value in improving the disease burden of LRIs.

Introduction In recent years, e-cigarettes as an emerging tobacco product have been favored by college students. Our study aims to explore the factors affecting the use of e-cigarettes among college students and to put forward feasible suggestions for effectively controlling the use of e-cigarettes among college students. Methods The participating students were from three undergraduate and three specialized colleges in Guangdong Province, surveyed from January to March 2022. The Fuzzy-set Qualitative Comparative Analysis (fsQCA) method was used to analyze the influence mechanism and path of five antecedents: selfefficacy, social environment, cognition, sales environment, and negative outcome expectation, on the use of e-cigarettes. The fsQCA used in this study is a novel research methodology that combines the strengths of qualitative and quantitative analyses, through which we can determine which conditions are essential to the outcomes that lead to e-cigarette use among college students, and which combinations of conditions are more important than others. Results The interaction of self-efficacy, social environment, cognition, sales environment, and negative outcome expectation, affected college students’ use of e-cigarettes. Through the fsQCA method, it was found that self-efficacy alone constitutes a necessary condition for college students not to use e-cigarettes. There are four possible pathways for college students not to use e-cigarettes, with higher self-efficacy, correct cognition, and a healthy social environment influencing the most important combination of conditions for college students to use e-cigarettes. Conclusions The use of e-cigarettes by students in Guangdong Province is the result of the synergistic effect of multiple factors. Tobacco control action suggestions focus on improving students' self-efficacy and paying attention to the combination of different factors to achieve more effective tobacco control.

Abstract A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.

Abstract Background The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). Methods A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. Results (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3−CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3−CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. Conclusions RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. Trial registration The research was registered at the First Affiliated Hospital of Soochow University. Registration Number: MR-32-23-016211. Registration Date: May 31, 2023.

Abstract The development of highly efficient electrocatalysts for direct seawater splitting with bifunctionality for inhibiting anodic oxidation reconstruction and selective oxygen evolution reactions is a major challenge. Herein, we report a direct seawater oxidation electrocatalyst that achieves long-term stability for more than 1000 h at 600 mA/cm2@η600 and high selectivity (Faraday efficiency of 100%). This catalyst revolves an amorphous molybdenum oxide layer constructed on the beaded-like cobalt oxide interface by atomic layer deposition technology. As demonstrated, a new restricted dynamic surface self-reconstruction mechanism is induced by the formation a stable reconstructed Co-Mo double hydroxide phase interface layer. The device assembled into a two-electrode flow cell for direct overall seawater electrolysis maintained at 1 A/cm2@1.93 V for 500 h with Faraday efficiency higher than 95%. Hydrogen generation rate reaches 419.4 mL/cm2/h, and the power consumption (4.62 KWh/m3 H2) is lower than that of pure water (5.0 KWh/m3 H2) at industrial current density.

Dolomite formation is a crucial aspect of natural gas reservoirs in the marine strata of the Sichuan Basin, particularly in the exploration of deep carbonate reserved oil and gas resources. Understanding the genetic mechanism of dolomite is essential for predicting the distribution of favorable dolomite reservoirs in deep formations. Taking the third member of the Maokou Formation in the southeastern Sichuan Basin as an example, present work systematically investigates the genetic mechanism of dolomite by analyzing geochemical characteristics such as carbon and oxygen isotopes, strontium isotopes and rare earth elements. The analysis is based on data from outcrops, core samples and thin sections. The results reveal that the dolomites of the third member of the Maokou Formation in the southeastern Sichuan Basin can be categorized into laminated fine-crystalline dolomite, laminated fine to medium-crystalline dolomite, and saddle dolomite cement. Among these, the laminated fine to medium-crystalline dolomite is the most common type. The δ18O values of this dolomite type (-7.04‰ to -6.08‰) appeared unaffected by hydrothermal fluids, and are similar to those of mud-crystal limestone. Additionally, the 87Sr/86Sr ratio (0.707 550 to 0.707 740) locate within the range of contemporaneous seawater, indicating a diagenesis process of quasi-syngenetic to burial-induced restricted marine water infiltration dolomitization. The δ18O values of hydrothermally influenced dolomite range from -7.33‰ to -7.11‰, showing slightly negative compared to those of mud-crystal limestone. These dolomites also showed relatively higher 87Sr/86Sr ratios (0.707 950 to 0.708 171) than those of contemporaneous seawater. The laminated fine-crystalline dolomite, which was not affected by hydrothermal fluids, shares a common genetic mechanism with the previously mentioned laminated fine to medium-crystalline dolomite. Saddle dolomite cement found in caves and fractures is either directly precipitated or recrystallized from hydrothermal fluids. This type of dolomite is characterized by higher 87Sr/86Sr ratios (with a mean value of 0.707 970), significantly negative δ18O values (with a mean value of -7.32‰), and positive Eu anomalies. A gradient change from laminated fine-crystalline dolomite to laminated fine to medium-crystalline dolomite and finally to saddle dolomite cement is observed, controlled by a transition from marine water to hydrothermal fluids. The dolomite in the study area is proposed to be the product of multi-stage fluid-induced diagenesis.

To improve high-temperature oxidation resistance for Ti6Al4V alloy, AlxCoCrCuyFeNi (x = 0, 0.3, 0.5, 0.7, 1.0; y = 1.0, 0.7, 0.5, 0.3, 0, x + y = 1.0) high-entropy alloy (HEA) coatings were prepared on the Ti6Al4V alloy substrate by a laser cladding technique. The results show that the coatings were mainly composed of FCC, BCC, and Ti-rich phases. Severe segregation of the Cu element occurred in the CoCrCuFeNi HEA coatings as a Cu-rich phase (FCC2). The Cu-rich phases decreased with a decreasing Cu content and completely disappeared until the Al content reached 1.0. The microhardnesses of the Cu1.0, Cu0.7Al0.3, Cu0.5Al0.5, Cu0.3Al0.7, and Al1.0 HEA coatings were 2.01, 2.06, 2.08, 2.09, and 2.11 times that of the substrate, and compared with those of a Ti6Al4V alloy substrate, the oxidation rates of the HEA coatings decreased by 55%, 51%, 47%, 42%, and 35%, respectively. The surface oxides of the five coatings were mainly composed of CuO, TiO2, Fe3O4, Cr2O3, and Al2O3. The increase in the Al content promoted the generation of Al2O3 film and Cr2O3 on the surfaces of the coatings, which significantly improved the high-temperature antioxidant performance of the high-entropy alloy coatings for 50 h at 800 °C. When x = 1.0, the coating showed the best high-temperature antioxidant performance.

Fertilization can improve soil nutrition and increase the yield of Sapindus mukorossi, but the response of soil microbial communities to fertilization treatments and their correlation with soil nutrition and Sapindus mukorossi yield are unclear. In order to investigate the characteristics of soil physicochemical qualities and the bacterial community, we carried out a field experiment comparing various quantities of nitrogen (N), phosphorus (P), and potassium (K) fertilizers to the unfertilized control treatments and the yield of Sapindus mukorossi in raw material forests in response to different applications of fertilizers and to try to clarify the interrelation among the three. Results showed that (1) there are significant differences in the effects of different fertilization treatments on the soil properties of Sapindus mukorossi raw material forests. The increase in the application rates of nitrogen or phosphorus fertilizers significantly reduced the soil pH value. (2) Compared with control, the α-diversity of bacterial communities was significantly lower in N3P2K2 and N1P1K2 treatments. Among the dominant groups of soil bacteria at the phylum level, the relative abundance of Chloroflexi showed an increase and then a decrease trend with the increase in N application. The relative abundance of Firmicutes, Bacteroidota, and Fusobacteriota was positively correlated with the application of P and K fertilizers, while the relative abundance of Acidobacteriota and Verrucomicrobiota decreased with the increase in P and K fertilizers. (3) The N2P2K2 treatment produced the highest sapindus yield (1464.58 kg/ha), which increased by 258.67% above the control. (4) Redundancy analysis (RDA) showed that the primary determinants of bacterial community structure were soil pH, total K, and effective P concentration. (5) Structural equation modeling (SEM) showed that soil nutrient content was the main direct factor driving the yield of Sapindus mukorossi, whereas the bacterial community attributes (e.g., diversity and structure) had minor effects on the yield. In summary, the rational use of formulated fertilization can change the bacterial community structure, improve the bacterial diversity, and increase the soil nutrient content, with the latter exerting a significant effect on the improvement of the yield of Sapindus mukorossi.

Background: Severe endometrial injury constitutes a significant risk to female fertility, often leading to the development of intrauterine adhesions. Pyroptosis, a form of programmed cell death associated with inflammation, is initiated by the cleavage of gasdermin family proteins by caspase, which has been implicated in endometrial injury. In recent years, hydrogen sulfide (H2S), a gaseous signaling molecule, exerts significant regulatory effects on pyroptosis in diverse pathological processes. The aim of this study is to elucidate the role of H2S in facilitating functional recovery of the endometrium following injury in a murine model. Methods: A prospective laboratory based randomized control trial was performed to evaluate the protective role of H2S in endometrial injury. Ethanol-induced endometrial injury mouse models were established and H2S donor sodium hydrosulfide (NaHS) was randomly administered to the injured mice. Western blot analysis was conducted to assess changes in the expression of endogenous H2S metabolism and pyroptosis-related markers and histological analysis (Hematoxylin & Eosin and Masson staining) was employed to examine alterations in endometrial morphology. Finally, a fertility test was performed to evaluate the restoration of the uterine function. Results: Following endometrial injury, the expression of key endogenous H2S enzymes-cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)-is significantly reduced, while the levels of pyroptosis-related proteins are elevated (p < 0.05). However, treatment with H2S resulted in an increase in the expression of endogenous H2S enzymes and a decrease in pyroptosis-associated proteins compared to the Model group (p < 0.05). Moreover, endometrial morphology and embryo count showed the most pronounced improvement in the H2S treatment group (p < 0.05). Conclusions: This study confirms the therapeutic efficacy of H2S in facilitating the recovery of injured endometrium and revealed its potential therapeutic mechanism, offering a promising therapeutic avenue for patients with severe endometrial injury.

The global incidence of atrial fibrillation is on the rise. Atrial fibrillation, a complex disease, heightens the likelihood of heart failure, stroke, and mortality, necessitating careful attention. Controlling heart rate and rhythm, addressing risk factors, and preventing strokes are fundamental in treating atrial fibrillation. Catheter ablation stands out as the primary approach for atrial fibrillation rhythm control. Nevertheless, the limited success rates pose a significant challenge to catheter ablation, particularly for persistent atrial fibrillation. Various adjunctive ablation techniques are currently under investigation to enhance the effectiveness of catheter ablation. This review provides an overview of the current state of the art and the latest optimized treatments for persistent atrial fibrillation in the areas of rhythm control, heart rate control, and risk factor management.

Dielectric elastomer actuators (DEAs) are increasingly recognized for their potential in robotic applications due to their ability to undergo significant deformation when subjected to an electric field. However, they are often limited by their low output power, which can make their integration into dynamic systems like hopping robots particularly challenging. This research optimizes the performance by introducing a cone DEA with a novel type of semi-diamond preload mechanism. This type of preload mechanism can meet the requirements of a negative-stiffness preload and a light weight. According to the experiments, the DEA can provide 3.62 mW power and its mass is only about 17.5 g. In order to drive hopping robots based on a cone DEA, this research introduces an energy accumulation mechanism coupled with a constant-torque cam for a hopping robot. The hopping robot weighs approximately 30.3 g and stands 10 cm tall in its upright position. Its energy accumulation mechanism involves a gear and cam transmission system, which is the key to store and release energy efficiently. The primary components of this mechanism include a torsion spring that stores mechanical energy when twisted, a constant-torque actuation cam that ensures the consistent application of torque during the energy storage phase, and a conical DEA that acts as an actuator. When the conical DEA is activated, it pushes a one-way clutch to the rocker, rotating the gear and cam mechanism and subsequently twisting the torsion spring to store energy. Upon release, the stored energy in the torsion spring is rapidly converted into kinetic energy, propelling the robot into the air. The experiments reveal that the designed DEA can drive the hopping robot by using the energy storage mechanism. Its hopping height is related to the pre-compression angle of the torsion spring. The DEA can drive the rigid hopping mechanism, and the maximum hopping height of the robot is up to 2.5 times its height. DEA hopping robots have obvious advantages, such as easy control, quietness and safety.

Ethnopharmacological relevance: Vitamin D (VD), selenium preparations (Se), and thyroid hormone replacement therapy are commonly used to treat Hashimoto thyroiditis (HT). Increasing evidence suggests that traditional Chinese medicine (TCM) is an effective therapeutic strategy in the treatment of HT. Aim of the study: This study aimed to investigate the efficacy and safety of commonly-used drugs for HT. Materials and methods: A literature search was performed using PubMed, Web of Science, Cochrane Library, EMBASE, Chinese China National Knowledge Infrastructure (CNKI), Clinical Trial Registry (Chi CTR), China Science and Technology Journal Database (the VIP), Wanfang Database, and China Chinese Biomedical Database (CBM) from January 1, 2003, to December 31, 2022. The outcomes included TPOAb, TgAb, TSH, FT3, FT4, and adverse events. Our study was registered in PROSPERO (CRD42023449705). Results: Sixty trials and 4719 participants were included, comparing 16 treatments: VD, Se, LT-4, Se + LT-4, HM, placebo + LT-4, HM + LT-4, Se + myolnositol, Se + VD, HM + Se, mannan peptide, LT-4+prednisone, Methimazole, Methimazole + HM, Tapazole + Propranolol, and placebo. We found that Chinese herbal medicine has significant effect vs. LT-4 [MD 0.10, 95 % confidence interval 0.02 to 0.50]) and LT-4+placebo [MD 0.10, 95 % confidence interval 0.01 to 0.77]) in reducing TPOAb. Although receiving LT-4+prednisone was not statistically significant, the treatment ranking showed that this combination therapy had the highest probability of reducing TPOAb levels (72.8 %). In addition, the effect of Se plus LT-4 was not statistically significant; however, the treatment ranking showed that this combination therapy had the highest probability (78.6 %) of reducing TgAb levels, followed by HM (64.0 %). Reports on side effects have mainly focused on the digestive and cardiovascular systems. Conclusion: Our analyses showed that HM alone or in combination with other treatments for patients with HT can improve the side effects of other drugs, enhance efficacy, and maybe the most effective option for treating HT. However, there still need further verified using high-quality evidence.

Abstract Background Beta 2‐microglobulin (β2‐MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2‐MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2‐MG and LVH in T2DM patients. Methods The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non‐LVH groups based on echocardiography results. Serum β2‐MG levels were measured, and participants were categorized into four groups (Q1–Q4) by their serum β2‐MG quartile. The relationship of serum β2‐MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. Results The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2‐MG level corresponded to a 1.17‐fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05–1.31); p = 0.006]. When considering β2‐MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09–1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36–2.31); p

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research.Aim: To discuss the role of BBR in the whole body’s systemic metabolic regulation and further explore its therapeutic potential and targets.Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets.Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases.Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.

Objectives This study sought to evaluate the diagnostic value of a non-contact optical fiber mattress for apnea and hypopnea and compare it with traditional polysomnography (PSG) in adult obstructive sleep apnea hypopnea syndrome (OSAHS). Methods To determine the value of a non-contact optical fiber mattress for apnea and hypopnea, six healthy people and six OSAHS patients were selected from Tongji Hospital to design a program to identify apnea or hypopnea. A total of 108 patients who received polysomnography for drowsiness, snoring or other suspected OSAHS symptoms. All 108 patients were monitored with both the non-contact optical fiber mattress and PSG were collected. Results Six healthy controls and six patients with OSAHS were included. The mean apnea of the six healthy controls was 1.22 times/h, and the mean hypopnea of the six healthy controls was 2 times/h. Of the six patients with OSAHS, the mean apnea was 12.63 times/h, and the mean hypopnea was 19.25 times/h. The non-contact optical fiber mattress results showed that the mean apnea of the control group was 3.17 times/h and the mean hypopnea of the control group was 3.83 times/h, while the mean apnea of the OSAHS group was 11.95 times/h and the mean hypopnea of the OSAHS group was 17.77 times/h. The apnea index of the non-contact optical fiber mattress was positively correlated with the apnea index of the PSG (P < 0.05, r = 0.835), and the hypopnea index of the non-contact optical fiber mattress was also positively correlated with the hypopnea index of the PSG (P < 0.05, r = 0.959). The non-contact optical fiber mattress had high accuracy (area under curve, AUC = 0.889), specificity (83.4%) and sensitivity (83.3%) for the diagnosis of apnea. The non-contact fiber-optic mattress also had high accuracy (AUC = 0.944), specificity (83.4%) and sensitivity (100%) for the diagnosis of hypopnea. Among the 108 patients enrolled, there was no significant difference between the non-contact optical fiber mattress and the polysomnography monitor in total recording time, apnea hypopnea index (AHI), average heart rate, tachycardia index, bradycardia index, longest time of apnea, average time of apnea, longest time of hypopnea, average time of hypopnea, percentage of total apnea time in total sleep time and percentage of total hypopnea time in total sleep time. The AHI value of the non-contact optical fiber mattress was positively correlated with the AHI value of the PSG (P < 0.05, r = 0.713). The specificity and sensitivity of the non-contact optical fiber mattress AHI in the diagnosis of OSAHS were 95% and 93%, with a high OSAHS diagnostic accuracy (AUC = 0.984). Conclusion The efficacy of the non-contact optical fiber mattress for OSAHS monitoring was not significantly different than PSG monitoring. The specificity of the non-contact optical mattress for diagnosing OSAHS was 95% and its sensitivity was 93%, with a high OSAHS diagnostic accuracy.

Objective: Chronic kidney disease (CKD) related to obstructive sleep apnea-hypopnea syndrome (OSAHS) mainly results from chronic intermittent hypoxia (CIH)-induced renal injury. This study aimed to explore the interaction between the long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) and recombinant adenine phosphoribosyltransferase (APRT) in CIH-induced renal injury. Methods: A rat intermittent hypoxia model was constructed, total RNA was extracted from kidney tissue, and transcriptome sequencing was performed using high-throughput sequencing technology. CIH rat models were established and injected with sh-GAS5 or OE-APRT plasmid, the serum levels of blood urea nitrogen (BUN) and creatinine amidohydrolase were measured, and the expression of oxidative stress-related factors was detected. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used for morphological observations, and cell apoptosis was determined by TUNEL staining. Interactions between GAS5, TATA-box binding protein-associated factor 1 (TAF1), and APRT were predicted and verified. After transfection of HK-2 cells, the expression of GAS5, TAF1, APRT, Bax, Bcl-2, apoptosis-related factors, fibrosis-related factors (collagen I and Ⅳ), and autophagy-related proteins (LC3-Ⅱ, LC3-Ⅰ, p62, and Beclin-1) was measured by RT-qPCR and western blotting. Results: Sequencing results revealed that TAF1 was significantly increased and APRT was significantly decreased in the CIH group. RNA was significantly involved in the biological process of kidney injury mediated by CIH. CIH rats injected with GAS5 suppression or APRT overexpression plasmids showed decreased GAS5 and elevated APRT expression, along with suppressed serum levels of BUN and creatinine amidohydrolase. Meanwhile, GAS5 suppression or APRT overexpression attenuated apoptosis and fibrosis, suppressed oxidative stress, and promoted autophagy in CIH-induced renal tubular epithelial cells. The RNA pull-down assay and RIP verified the binding and interaction of GAS5 and TAF1. Chip immunoprecipitation (ChIP) identified TAF1 regulation of the APRT promoter. GAS5 and TAF1 negatively regulated APRT expression. Conclusion: The lncRNA GAS5 can bind TAF1 to suppress APRT transcription, thereby enhancing CIH-induced renal injury in rats.