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Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix (GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix (PR, Platycodon grandiflorum A. DC) and its potential mechanism for treating respiratory syncytial virus (RSV) pneumonia in mice. Materials and Methods: Aqueous extracts of GR-PR with different ratios (1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of inflammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung inflammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin (SM) and ceramide (CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced inflammation and apoptosis, along with decreased mRNA levels of caspase-1, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3), and toll-like receptor 3 (TLR3), and protein expression of NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin-1β (IL-1β), IL-18, gasdermin D (GSDMD), nuclear factor kappa-B (NF-κB), Bcl2-associated X protein (BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

This is an article in the field of mineral processing engineering. Lithium ore is an important strategic resource in China. At present, flotation is the most commonly used method for the separation of lithium ore. In this article, the crystal structure characteristics of spodumene and its interaction mechanism with flotation agent are discussed from the point of view of spodumene crystal structure. This article describes it from seven aspects: metal cationic activator, organic inhibitor, inorganic inhibitor, anionic collector, cationic collector, mixed collector and new collector. It is of great significance to understand the characteristics of the interaction between spodumene and reagents, to develop new and efficient flotation reagents and to optimize the mineral processing process.

Abstract Gliomas represent the most predominant primary malignant tumor in central nervous system. Thymine DNA glycosylase (TDG) is a central component in active DNA demethylation. However, the specific mechanisms of TDG-mediated active DNA demethylation in gliomas remain unclear. This research indicates TDG expression is overexpressed in gliomas and correlated with poor prognosis. TDG knockdown suppressed the malignant phenotype of gliomas both in vitro and vivo. Notably, RNA-seq analysis revealed a strong association between TDG and tenascin-C (TNC). ChIP-qPCR and MeDIP-qPCR assays were undertaken to confirm that TDG participates in TNC active DNA demethylation process, revealing decreased DNA methylation levels and elevated TNC expression as a result. Silencing TNC expression also suppressed the tumor malignant phenotype in both in vitro and in vivo experiments. Additionally, simultaneous silencing of TNC reduced or even reversed the glioma promotion caused by TDG overexpression. Based on our findings, we conclude that TDG exerts an indispensable role in TNC active DNA demethylation in gliomas. The DNA demethylation process leads to alternations in TNC methylation levels and promotes its expression, thereby contributing to the development of gliomas. These results suggest a novel epigenetic therapeutic strategy targeting active DNA demethylation in gliomas.

Abstract Purpose The aim was to explore the preoperative and postoperative fibrinogen changes value (FCV) as a prognosis biomarker for in patients with adrenocortical carcinoma (ACC). Methods We identified 42 patients with ACC and 190 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2023. Preoperative fibrinogen, postoperative fibrinogen and follow-up information of the patients were recorded and analysed. The relationship between FCV and overall survival (OS)/ relapse-free survival (RFS) was evaluated. Results The mean level of preoperative and postoperative fibrinogen for ACC were 4.00 ± 1.64 g/L and 2.75 ± 0.59 g/L, respectively (p 1.25 g/L) (p = 0.007); however, the lower FCV (≤ 1.25 g/L) showed no poorer OS than the higher (> 1.25 g/L) (p = 0.243). On multivariate survival analyses, FCV remained a predictor of RFS (HR 3.138). Conclusion According to the data in this study, it can be said that FCV is correlated with prognosis of ACC. The FCV might be a new biomarker for predicting the RFS of ACC.

Abstract Purpose We developed a novel guider-assisted osteotomy (GAO) procedure to improve the safety of open wedge high tibial osteotomy (OWHTO) and aimed to compare its efficacy and complications with the conventional pendulum-saw osteotomy (PSO). Methods This is a retrospective cohort study of patients undergoing either GAO or PSO procedure in the OWHTO to treat varus knee osteoarthritis, who had a minimum of 2 years of follow-up. Patients were propensity score matched (PSM) in a 1:1 ratio based on demographic and clinical data with a caliper width of 0.02. The outcomes assessed involved the hospital for special surgery (HSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and the Intraoperative and postoperative complications. Results 199 patients were included in each group after PSM. The mean duration of follow-up was 38.3 ± 8.9 months. The GAO group had a shorter operation duration (104.5 ± 35.7 vs. 112.1 ± 36.0 min, p = 0.027) and fewer times of intraoperative fluoroscopy (4.2 ± 1.4 vs. 6.0 ± 1.4, p 0.05). In addition, the intraoperative complications (0.5% vs. 3.5%, p = 0.068) and the postoperative bone delayed union and nonunion (1.0% vs. 4.5%, p = 0.032) were marginally or significantly reduced in the GAO versus PSO group. Conclusion GAO demonstrates improvements in intraoperative radiation exposure and complications, with comparable short-term efficacy to PSO, and could be considered a viable alternative in clinical practice.

Abstract. Background:. Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. Methods:. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Results:. Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P

The βʹ-Cu4Ti phase is the major strengthening precipitate in Cu–Ti alloys. Previous research indicates that destabilization of the βʹ-Cu4Ti phase leads to dissolution of Ti atom from precipitates into the Cu matrix. In the present work, Sc was chosen to be alloying elements in Cu–Ti alloys, since stabilization of the βʹ-Cu4Ti phase could be enhanced by formation of βʹ-Cu4(Ti,Sc) phase. Experimental characterization combined with first-principles calculations were used to evaluate the effect of Sc addition. It was found that the bonding between Ti and Sc atoms in the same sublattice of βʹ-Cu4Ti phase increases the diffusion barrier of Ti atoms, and thus dissolution of the βʹ-Cu4Ti phase and further nucleation of the β-Cu4Ti phase were hindered.

Abstract Background Previous studies have shown that high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cognitive function across a range of concentrations. However, recent studies have suggested that very high HDL-C levels may lead to poorer outcomes. Therefore, we aimed to investigate the relationship between different concentrations of HDL-C and cognitive impairment risk. Methods We collected data from 3632 participants aged over 60 years from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 to assess the relationship between HDL-C and cognitive function. Cognitive function was evaluated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the animal fluency test (AFT), and the digit symbol substitution test (DSST). We used restricted cubic spline models and logistic regression to examine the association between HDL-C and cognitive function. Results A U-shaped was observed between HDL-C and cognitive outcomes, individuals with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (≥ 2.50 mmol/L) were associated with increased risk of cognitive impairment (OR = 2.19; 95% CI, 1.12–4.28) compared with those with HDL-C levels in the range of 1.50 to 1.99 mmol/L in older adults after adjustment for confounding factors. Interaction test demonstrated that relationship between very high HDL-C and the risk of cognitive impairment was not changed in different sex and race group (P for interaction > 0.05). Conclusions Very high HDL-C levels were associated with an increased risk of cognitive impairment. HDL-C may not be a protective factor for maintaining brain health in older adults at very high levels.

Abstract Background The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT. Methods Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT. Results 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01–2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size. Conclusion LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.

Abstract Background Postoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance. Methods This prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ2 test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables. Discussion The purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients’ postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment. Trial registration ClinicalTrials.gov NCT06281561. Registered on February 24, 2024.

Arsenic is commonly used in alloy materials and the semiconductor industry, and has promising applications. Arsenic and antimony have similar physicochemical properties, and their binding and separation mechanisms are unknown, thereby limiting the purification and preparation of arsenic. This study, from a microscopic perspective, reveals that arsenic and antimony covalently interact in alloys through a combination of thermodynamic analysis and molecular dynamics simulations. In addition, antimony as arsenic-antimony clusters enters the gas phase, and the diffusion coefficients of the clusters are in the order of As4>As3Sb > As2Sb2>AsSb3. A green and efficient vacuum sublimation-graded condensation process for arsenic purification is proposed based on the different diffusion coefficients to obtain the optimal process parameters. The coalescence of arsenic on a condenser was normally distributed. The removal rate of antimony in the most concentrated area of the condensate was 91.37% under the optimal conditions of 748 K, 60 min, and 10 Pa. Thus, the proposed method effectively solves the challenging problem of separating arsenic and antimony, and the study results provide theoretical support for purifying arsenic via vacuum sublimation.

The widespread implementation of surveillance systems on construction sites has led to the accumulation of vast amounts of visual data, highlighting the need for an effective semantic analysis methodology. Natural language, as the most intuitive mode of expression, can significantly enhance the interpretability of such data. The adoption of multi-modality models promotes the interaction between surveillance video and textual data, thereby enabling managers to swiftly comprehend on-site dynamics. This study introduces a Visual Question Answering (VQA) approach for the construction industry and presents a specialized dataset to address the unique requirements of on-site management. Utilizing a Vision Transformer (ViT) architecture, the proposed model conducts feature extraction, fusion and interaction between visual and textual features. An additional projection layer is added to establish a transfer learning strategy that is optimized for construction site data. This novel approach facilitates rapid alignment of visual and language features in the model and is validated through ablation studies. The proposed approach achieves a testing accuracy of 83.8%, effectively converting image data from construction sites into natural language descriptions that enhance the analysis of construction processes. Compared to existing methods, this approach does not rely on object detection and allows for the direct extraction of deep-level semantic information from the on-site images. This study further discusses the feasibility of applying VQA within the architecture, engineering and construction (AEC) industry, examines its limitations, and offers suggestions for viable future directions of development.

Abstract Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized treatment strategies. We computed enrichment stemness scores and performed consensus clustering to categorize phenotypes. Subsequently, we constructed a prognostic risk model using weighted gene correlation network analysis (WGCNA), random survival forest regression analysis as well as full subset regression analysis. To validate the expression differences of key genes, we employed experimental methods such as quantitative Polymerase Chain Reaction (qPCR) and assessed cell line proliferation, migration, and invasion. Three subtypes were assigned to patients diagnosed with LGG. Notably, Cluster 2 (C2), exhibiting the poorest survival outcomes, manifested characteristics indicative of the subtype characterized by immunosuppression. This was marked by elevated levels of M1 macrophages, activated mast cells, along with higher immune and stromal scores. Four hub genes—CDCA8, ORC1, DLGAP5, and SMC4—were identified and validated through cell experiments and qPCR. Subsequently, these validated genes were utilized to construct a stemness risk signature. Which revealed that Lower-Grade Glioma (LGG) patients with lower scores were more inclined to demonstrate favorable responses to immune therapy. Our study illuminates the stemness characteristics of gliomas, which lays the foundation for developing therapeutic approaches targeting CSCs and enhancing the efficacy of current immunotherapies. By identifying the stemness subtype and its correlation with prognosis and TME patterns in glioma patients, we aim to advance the development of personalized treatments, enhancing the ability to predict and improve overall patient prognosis.

Abstract The mechanical properties of rocks in cold regions undergo significant changes as a result of decades of freeze‒thaw cycles with seasonal variations, which can lead to a series of geological disasters, such as collapse. This study investigates the evolution of the mechanical characteristics and internal progressive damage characteristics of mixed granite under freeze‒thaw cycling and axial loading. By measuring the mass, wave velocity, and uniaxial compressive strength of rock samples and combining these metrics with acoustic emission (AE) characteristics, the physical and mechanical properties and microfracture development of mixed granite after different numbers of freeze‒thaw cycles were investigated. The results indicate that as the number of freeze‒thaw cycles increases, the longitudinal wave velocity, uniaxial compressive strength, and elastic modulus of the mixed granite decrease nonlinearly, while the peak strain gradually increases. Combined with the stress‒strain curve, the AE characteristics can be divided into four stages. As the number of freeze‒thaw cycles increases, the AE cumulative count decreases, and the AE counts of the four stages are different. The low-frequency-high-amplitude signals first increases and then tends to stabilize, and they only appeared in the third and fourth stages. At the same time, the proportion of the low-frequency ratio gradually increases, and the proportion of the high-frequency ratio decreases. In addition, based on the rise time/amplitude (RA) and average frequency (AF) characteristics and failure modes, it was found that the internal crack types of mixed granite transition from shear cracks to tensile cracks, among which tensile cracks play a crucial role in rock failure.

Rain gauge networks provide direct precipitation measurements and have been widely used in hydrology, synoptic-scale meteorology, and climatology. However, rain gauge observations are subject to a variety of error sources, and quality control (QC) is required to ensure the reasonable use. In order to enhance the automatic detection ability of anomalies in data, the novel multi-source data quality control (NMQC) method is proposed for hourly rain gauge data. It employs a phased strategy to reduce the misjudgment risk caused by the uncertainty from radar and satellite remote-sensing measurements. NMQC is applied for the QC of hourly gauge data from more than 24,000 hydro-meteorological stations in the Yangtze River basin in 2020. The results show that its detection ratio of anomalous data is 1.73‰, only 1.73% of which are suspicious data needing to be confirmed by experts. Moreover, the distribution characteristics of anomaly data are consistent with the climatic characteristics of the study region as well as measurement and maintenance modes of rain gauges. Overall, NMQC has a strong ability to label anomaly data automatically, while identifying a lower proportion of suspicious data. It can greatly reduce manual intervention and shorten the impact time of anomaly data in the operational work. HIGHLIGHTS Quantitative and fusion application of radar and satellite data were addressed for the quality control (QC) of hourly rain gauge data.; Precipitation quality anomaly events were defined to improve the traceability of QC.; A phased QC strategy was adopted to reduce the misjudgment risk caused by the uncertainty of remote-sensing measurements.;

Abstract The growth of plants is threatened by numerous diseases. Accurate and timely identification of these diseases is crucial to prevent disease spreading. Many deep learning-based methods have been proposed for identifying leaf diseases. However, these methods often combine plant, leaf disease, and severity into one category or treat them separately, resulting in a large number of categories or complex network structures. Given this, this paper proposes a novel leaf disease identification network (LDI-NET) using a multi-label method. It is quite special because it can identify plant type, leaf disease and severity simultaneously using a single straightforward branch model without increasing the number of categories and avoiding extra branches. It consists of three modules, i.e., a feature tokenizer module, a token encoder module and a multi-label decoder module. The LDI-NET works as follows: Firstly, the feature tokenizer module is designed to enhance the capability of extracting local and long-range global contextual features by leveraging the strengths of convolutional neural networks and transformers. Secondly, the token encoder module is utilized to obtain context-rich tokens that can establish relationships among the plant, leaf disease and severity. Thirdly, the multi-label decoder module combined with a residual structure is utilized to fuse shallow and deep contextual features for better utilization of different-level features. This allows the identification of plant type, leaf disease, and severity simultaneously. Experiments show that the proposed LDI-NET outperforms the prevalent methods using the publicly available AI challenger 2018 dataset.

Abstract. Background:. There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. Methods:. In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. Results:. At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P

Abstract Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.

Abstract Background The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation. Results In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period. Conclusions Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

In this paper, three kinds of Cu–Cr2O3 composites with different particle sizes were prepared from Cu-0.67 wt%Cr atomized alloy powder by supercritical water liquid phase in-situ oxidation (SW-LIO) through reduction and spark discharge plasma sintering (SPS). The structure and properties of the composites were systematically analyzed by X-ray diffractometer (XRD), scanning electron microscope (SEM), energy spectrometer, transmission electron microscope, electron backscattering diffraction, universal material testing machine, microhardness tester, eddy current conductometer, friction and wear testing machine, etc. The results show that Cr2O3 particles are evenly distributed in Cu matrix composites. The hardness of composites improved by 19% as the particle size decreased, while the tensile strength and electrical conductivity first increased as the particle size is refined. Meanwhile, the deformation behavior research is carried out, and the mechanical properties and electrical conductivity of composites are enhanced as the deformation amount increases.

Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent type. Accurately predicting NSCLC prognosis is crucial for optimizing patient survival. However, traditional assessment tools often lack the comprehensive and precise capability to effectively stratify patient risk. Recent research has focused on exploring the potential of imaging histology technology for NSCLC prognosis. This article delves into the core principles of imaging histology and reviews the current state of research on its application in predicting NSCLC outcomes.

Abstract The role of carbon emissions resulting from land use change in the compilation of national greenhouse gas emission inventories is of paramount significance. This study is centered on the Mianyang Science and Technology City New Area located in Sichuan Province, China. We used the CLUE-S model and Sentinel-2A remote sensing data from 2017 to simulate and validate land use changes in 2022. Based on this validation, we established three simulation scenarios: a baseline scenario, an agricultural development scenario, and a construction development scenario. Using remote sensing data from 2022, we projected the land use for 2030. We also used CO2 concentration data collected in 2022 and 2023, processed the data using ArcGIS and Python, and conducted a quantitative analysis of carbon emissions under each scenario. Ultimately, the accuracy of both measured and predicted CO2 values for 2023 was juxtaposed and authenticated, thus concluding the investigative cycle of this study. Key findings include: (1) The accuracy of the CLUE-S model in the study area was assessed using overall accuracy, quantity disagreement and allocation disagreement indexes. In 2022, the overall accuracy is 98.19%, the quantity disagreement is 1.7%, and the allocation disagreement is 2.2%. (2) Distinct land resource utilization characteristics in scenarios, highlighting potential impacts on economic development and pollution. (3) Increased carbon emissions across scenarios, with construction development showing the highest rise (4.170%) and agricultural development the lowest (0.766%). (4) The predictive accuracy of the validation group's CO2 concentration values can reach 99.5%. This study proposes precise CO2 prediction at the county level, thus laying the groundwork for future research endeavors. Such findings are indispensable for informing carbon policy formulation and promoting low-carbon development strategies.

Highlights The acid etching Co-naphthalenedicarboxylic acid-based metal–organic frameworks (donated as AE-CoNDA) catalyst displayed an excellent oxygen evolution reaction (OER) activity for long-term stability. Integration of the AE-CoNDA cocatalyst into BiVO4 achieved a remarkable PEC-OER activity. The stretched Co-O bond length regulated the spin state transition at the Co active sites. The optimized high spin state of Co sites adjusted the orbitals hybridization of Co 3d and O 2p.

Abstract Background Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. Methods We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein–protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. Results We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. Conclusions Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.

BackgroundMetagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method.MethodsA total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated.ResultsAmong 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched.ConclusionThrough this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.

Background: miRNA has been implicated in regulating cholesterol homeostasis, a critical factor in gallstone formation. Here, we focused on elucidating the role of miR-146a in this pathological process. Methods: C57BL/6 mice were fed with lithogenic diet (LD) and injected with miR-146 antagomir (anta-146) via the tail vein for various weeks. The gallbladders and liver tissues were collected for cholesterol crystal imaging, gallstone mass quantification, and molecular analysis. Levels of cholesterol, bile salt, phospholipids, and metabolic parameters in serum and bile were assessed by ELISA. A 3′ UTR reporter gene assay was used to verify the direct target genes for miR-146. The relative expression of metabolism genes was analyzed by quantitative real-time PCR and immunoblotting. Results: miR-146a-5p expression was reduced in mice and clinical samples with gallstones. Anta-146 treatment effectively prevented LD-induced gallstone formation in mice without hepatic and cholecystic damage. The mice treated with anta-146 exhibited beneficial alterations in bile cholesterol and bile acids and lipid levels in the blood. A key biliary cholesterol transporter-Megalin was identified as a direct target of miR-146. Anta-146 administration upregulated megalin expression, thereby ameliorating impaired gallbladder cholesterol absorption associated with the LXR-megalin/cubilin pathway. Conclusion: The data demonstrates that miR-146 modulates gallbladder cholesterol absorption by targeting megalin, and prevents the pathogenesis of cholesterol gallstones.

Traditional Chinese Exercise (TCE) has been shown to improve quality of life, and functional magnetic resonance imaging (fMRI) is a highly used method for investigating its mechanism. However, there is currently a lack of systematic reviews and meta-analyses focusing on TCE-related brain changes. This study aims to fill this gap by conducting a meta-analysis on brain changes of TCE with fMRI technology. We searched relevant studies published until February 2024. Independent researchers conducted literature screening, quality assessment, and clinical and neuroimaging data extraction. Focis were filtered from eligible studies, and meta-analysis was performed using seed-based d mapping. Twenty-three studies involving 1182 participants were included in this study. The result found that longitudinal TCE increased brain activity in the left anterior cingulate gyri, right fusiform gyrus, right middle temporal gyrus, left middle occipital gyrus and left frontal superior compared with other exercises or healthcare. Subgroup analysis showed that the brain activity in the right superior frontal gyrus dorsolateral; right cortico-spinal projections; corpus callosum; right inferior network; right gyrus rectus; left middle occipital gyrus were decreased after TCE compared to other exercise among healthy participants. The right median cingulate gyri was increased after Baduanjin (one of the TCE) compared to other exercise; the left precentral gyrus activity was increased after Tai chi chuan (TCC) practice compared to other exercise. The brain activity in the right insula, right supplementary motor area, and left anterior thalamic were significantly increased after long-time TCC exercise. TCE effectively improved the cognitive level of the subjects. Among them, the MoCA score increased, but Memory Quotient was not improved. Research results indicate that TCE have specific neuromodulatory effects, and different TCE have different neuromodulatory patterns.

Background: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio. Methods: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression. Results: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio. Conclusion: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

Based on the wide interlayer distance for ions diffusion, iron (II) oxalate exhibits excellent lithium storage ability. However, the local deposition of metallic nanoparticles of Fe0 leads to low electrochemical reactivity, which hinders the actual application of FeC2O4 in large current regions (>5C). To solve this problem, a strong cationic polymeric electrolyte, polyelectrolyte diallyl dimethyl ammonium (PDDA), was introduced to construct a [FeC2O4(PDDA)]+ ligand. By single-polymerization‐induced electrostatic self-assembly, the [FeC2O4(PDDA)]+ ligand was combined with the surface-charged rGO to produce a FeC2O4/rGO material. It is proved that the rGO carrier improves the interparticle conductivity, electrochemical activity and structure stability of the iron (II) oxalate particles, ensuring the stability of Li || FeC2O4/rGO battery at a rapid charging rate of 20C (8 A g−1) for more than 500 cycles (with the special capacity of 713 mAh g−1). Compared with FeC2O4 electrode, owning to high reactivity of rGO and continuously activating on the nanoscale Fe metal generated at ∼0.75 V, FeC2O4/rGO shows higher electrochemical activity of conversion reaction in the first 50 cycles and better reversibility in the rate charge–discharge test (the capacity rapidly increased to 1158.8 mAh g−1 after 20C cycles). This work reveals how the structural design of conducting and supporting the carrier can achieve fast charging for iron (II) oxalate lithium-ion batteries.

The utilization of radiant floor systems is one effective method to address the increasing cooling demand. The radiant floor cooling system (RFCS) has self-regulating capabilities, which benefit grid stability and the use of renewable energy. The application performance of RFCS is based on system design and intelligent control, as systems with high thermal inertia make it difficult to provide ideal indoor response effects. Therefore, this review aims to summarize the current development status of RFCSs and evaluate future development directions based on relevant research trends. A comprehensive overview of the radiant floor structure and the composition of RFCS were provided. The type of radiant floor structures can bring greater possibilities for the application of RFCS. Then, system control and evaluation are analyzed, with research on anti-condensation of radiant floors mainly focused on system and environmental control. Based on application status of the RFCS, the impact of various factors is discussed, including condensation risks, and climate change. Resistance to disturbances not only requires implementing control measures but also integrating with the building environment. There is still great potential for the hardware design and multi-directional integration of RFCS. The results of this review help relevant researchers gain a comprehensive understanding of the current development status and prospects of RFCS contributing to the decarbonization of the construction industry.

Summary: The human skin maintains a comfortable and healthy somatosensory state by sensing different aspects of the thermal environment, including temperature value, heat source, energy level, and duration. However, state-of-the-art thermosensors only measure basic temperature values, not the full range of the thermosensation function of human skin. Here, we propose a heat source recognition (hsr) sensor of poly(butyl acrylate)-lithium bis(n-fluoroalkylsulfonyl)imide (PBA-Li:nFSI; n = 1, 3, 5), which enables response to temperature, pressure, and proximity stimulus signals based on the relaxation behavior of the ionic gel and distinguished between different types of heat sources (i.e., radiation, convection, and conduction). The hsr sensor was integrated into a prosthetic limb covered by an e-skin with isothermal regulation, and experiments with a robot showed that it could achieve human-like thermosensation function, recognizing multidimensional information about thermal environments, such as temperature value, comfort level, and heat source signal. This work deeply mimics the human body’s thermosensation function and provides a reliable solution for the development of bionic e-skin for intelligent robots and prosthetics.

The release of host mitochondrial cardiolipin is believed to be the main factor that contributes to the production of anti-cardiolipin antibodies in syphilis. However, the precise mechanism by which mitochondria release cardiolipin in this context remains elusive. This study aimed to elucidate the mechanisms underlying mitochondrial cardiolipin release in syphilis. We conducted a cardiolipin quantitative assay and immunofluorescence analysis to detect mitochondrial cardiolipin release in human microvascular endothelial cells (HMEC-1), with and without Treponema pallidum (Tp) infection. Furthermore, we explored apoptosis, a key mechanism for mitochondrial cardiolipin release. The potential mediator molecules were then analyzed through RNA-sequence and subsequently validated using in vitro knockout techniques mediated by CRISPR-Cas9 and pathway-specific inhibitors. Our findings confirm that live-Tp is capable of initiating the release of mitochondrial cardiolipin, whereas inactivated-Tp does not exhibit this capability. Additionally, apoptosis detection further supports the notion that the release of mitochondrial cardiolipin occurs independently of apoptosis. The RNA-sequencing results indicated that microtubule-associated protein2 (MAP2), an axonogenesis and dendrite development gene, was up-regulated in HMEC-1 treated with Tp, which was further confirmed in syphilitic lesions by immunofluorescence. Notably, genetic knockout of MAP2 inhibited Tp-induced mitochondrial cardiolipin release in HMEC-1. Mechanically, Tp-infection regulated MAP2 expression via the MEK-ERK-HES1 pathway, and MEK/ERK phosphorylation inhibitors effectively block Tp-induced mitochondrial cardiolipin release. This study demonstrated that the infection of live-Tp enhanced the expression of MAP2 via the MEK-ERK-HES1 pathway, thereby contributing to our understanding of the role of anti-cardiolipin antibodies in the diagnosis of syphilis.

Septic arthritis (SA) is more severe in patients with rheumatoid arthritis, joint surgical issues, or a weakened immune system. Timely diagnosis of SA is crucial for effective treatment. Traditional diagnostic methods such as ELISA, white blood cell counting, blood culture, qPCR, and imaging techniques are often less accurate and time-consuming. Researchers are focusing on developing highly sensitive biosensors for SA using blood-based biomarkers. Procalcitonin is a protein and a well-established biomarker for SA. This research focuses on developing a procalcitonin interdigitated electrode (IDE) biosensor using a probe made of an aptamer and antibody-modified gold nanoparticle (AuNP) complex. The probe was attached to the IDE through an amine linker and then interacted with procalcitonin. AuNPs increased the attachment of the aptamer and antibody to the IDE, enabling the detection of procalcitonin at levels as low as 10 ng/mL, with a linear regression curve ranging from 10 to 100 ng/mL [y = 4.0691x - 2.1887; R2 = 0.9937]. Furthermore, procalcitonin-spiked serum elevated the current level with increasing procalcitonin concentrations, while control performances did not enhance the current, indicating the selective and specific detection of procalcitonin. This AuNP-aptamer-antibody complexed biosensor effectively identifies procalcitonin at low levels and aids in the diagnosis of SA.

Background and ObjectiveCoronary artery disease remains a leading cause of mortality among individuals with cardiovascular conditions. The therapeutic use of bioresorbable vascular scaffolds (BVSs) through stent implantation is common, yet the effectiveness of current BVS segmentation techniques from Intravascular Optical Coherence Tomography (IVOCT) images is inadequate.MethodsThis paper introduces an enhanced segmentation approach using a novel Wavelet-based U-shape network to address these challenges. We developed a Wavelet-based U-shape network that incorporates an Attention Gate (AG) and an Atrous Multi-scale Field Module (AMFM), designed to enhance the segmentation accuracy by improving the differentiation between the stent struts and the surrounding tissue. A unique wavelet fusion module mitigates the semantic gaps between different feature map branches, facilitating more effective feature integration.ResultsExtensive experiments demonstrate that our model surpasses existing techniques in key metrics such as Dice coefficient, accuracy, sensitivity, and Intersection over Union (IoU), achieving scores of 85.10%, 99.77%, 86.93%, and 73.81%, respectively. The integration of AG, AMFM, and the fusion module played a crucial role in achieving these outcomes, indicating a significant enhancement in capturing detailed contextual information.ConclusionThe introduction of the Wavelet-based U-shape network marks a substantial improvement in the segmentation of BVSs in IVOCT images, suggesting potential benefits for clinical practices in coronary artery disease treatment. This approach may also be applicable to other intricate medical imaging segmentation tasks, indicating a broad scope for future research.

Abstract Crustal deformation and hydrothermal percolation related to the India‐Asia collision have caused extensive remagnetization of the Tethyan Himalaya Terrane (THT). The present work identified three phases of regional remagnetization during 62.3–50.0 Ma for the east‐central THT. Consequently, a model of three‐stage India‐Asia collision was proposed. The east‐central THT first collided with the southward migrated southern margin of the Lhasa Terrane (LT) at 5.4 ± 0.9°N during 62.3–60.9 Ma. Subsequently, the THT continuously moved northward and pushed the southern margin of the LT back to its original position prior to the initiation of fore‐arc and back‐arc extension on both sides of the Gangdese magmatic arc. Since the final suturing of the THT with Asia at ∼10°N during 59.8–58.0 Ma, the east‐central THT remained stationary until India collided with it at 10.9 ± 5.1°N at ∼50.0 Ma.

BackgroundIn the ongoing battle against breast cancer, a leading cause of cancer-related mortality among women globally, the urgent need for innovative prognostic markers and therapeutic targets is undeniable. This study pioneers an advanced methodology by integrating machine learning techniques to unveil a vascular mimicry signature, offering predictive insights into breast cancer outcomes. Vascular mimicry refers to the phenomenon where cancer cells mimic blood vessel formation absent of endothelial cells, a trait associated with heightened tumor aggression and diminished response to conventional treatments.MethodsThe study’s comprehensive analysis spanned data from over 6,000 breast cancer patients across 12 distinct datasets, incorporating both proprietary clinical data and single-cell data from 7 patients, accounting for a total of 43,095 cells. By employing an integrative strategy that utilized 10 machine learning algorithms across 108 unique combinations, the research scrutinized 100 existing breast cancer signatures. Empirical validation was sought through immunohistochemistry assays, alongside explorations into potential immunotherapeutic and chemotherapeutic avenues.ResultsThe investigation successfully identified six genes related to vascular mimicry from multi-center cohorts, laying the groundwork for a novel predictive model. This model outstripped the prognostic accuracy of traditional clinical and molecular indicators in forecasting recurrence and mortality risks. High-risk individuals identified by our model faced worse outcomes. Further validation through IHC assays in 30 patients underscored the model’s extensive applicability. Notably, the model unveiled varying therapeutic responses; low-risk patients might achieve greater benefits from immunotherapy, whereas high-risk patients demonstrated a particular sensitivity to certain chemotherapies, such as ispinesib.ConclusionsThis model marks a significant step forward in the precise evaluation of breast cancer prognosis and therapeutic responses across different patient groups. It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management.

Study region: The source region of the Yangtze River in the Qinghai-Tibet Plateau, China. Study focus: In the context of global warming, conducting a comprehensive study on the hydrothermal processes and their influencing factors in the permafrost active layer of the Tibetan Plateau is crucial for gaining a better understanding of the ecohydrological processes in alpine grasslands. In this study, we analyzed differences in soil temperature and humidity change patterns in the active layer of four alpine grassland types in the Totuohe Basin of the Yangtze River source area. We aimed to discuss the influence of vegetation, soil, and other factors on the hydrothermal mechanism of the active layer. The main research results are as follows: (1) Significant differences in the active layer's hydrothermal regime, with higher vegetation cover correlating to lower thaw indices and better moisture conditions. (2) Vegetation and water content strongly influence thermal conditions and active layer thickness. In high-cover alpine meadows, ground surface temperature is lower with a 200 cm active layer, while swamp meadows have a shallowest layer at 160 cm. (3) Deeper active layer moisture is influenced by freezing and thawing, while shallower layers are affected by warm-season precipitation and soil texture. (4) Negative heat fluxes in the topsoil of alpine swamp and high-cover meadows indicate substantial heat release, likely contributing to permafrost preservation due to high active layer water content. New hydrological insights for the region: (1) Vegetation cover significantly influences the thermal and moisture conditions of the active layer, with higher vegetation associated with lower thaw indices and better moisture conditions.(2) Soil moisture distribution within the active layer is controlled by both freeze-thaw cycles and warm-season precipitation, indicating complex interactions between seasonal processes and soil properties.

ObjectiveThis research aims to investigate the levels of lymphocytes, immunoglobulins, and cytokines in children with infantile spasms (IS) before and after adrenocorticotropic hormone (ACTH) therapy and to explore the application of these markers in evaluating the therapeutic effects of ACTH on infantile spasms.MethodsFrom May to November 2022, 35 children initially diagnosed with IS and treated at our hospital were regarded as the observation group, and 35 healthy children who underwent physical examination at our hospital during the same period were regarded as the control group. Children in the observation group received intramuscular injections of ACTH for 2 weeks. Fasting venous blood was collected from the control group and the observation group before and after ACTH therapy. Serum levels of immunoglobulins IgG, IgA, and IgM in serum were detected by immunoturbidimetry. T-cell subsets (CD3+, CD3+CD4+, and CD3+CD8+) and B-cell subsets [CD3−CD19+ and CD3−CD16+CD56+ natural killer (NK) cells] were detected by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. Serum levels of interleukin-1β (IL-1β), interleukin-2R (IL-2R), and interleukin-6 (IL-6) cytokines were detected by the enzyme-linked immunosorbent assay, and changes in serum cytokine and immunoglobulin levels in the two groups were compared before therapy, whereas in observation group one, these comparisons were made both before and after ACTH therapy.ResultsCompared to the control group, the observation group showed significantly increased serum levels of immunoglobulins IgG and IgM before therapy, while the level of IgA was significantly decreased (p 0.05); the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly increased (p 0.05). The percentages of CD3+ T cells and CD3+CD4+ T cells were significantly increased, while the percentages of CD3−CD16+CD56+ NK cells and CD3−CD19+ B cells were significantly decreased (p 0.05). Furthermore, the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly reduced (p

Introduction Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its feasibility and safety remain uncertain, as only a few retrospective studies have contained postoperative complications and long-term survival data. LPG-DFT for proximal early gastric cancer is still in the early stages of research. Large-scale, prospective randomised controlled trials (RCTs) are necessary to assess the value of LPG-DFT for proximal early gastric cancer.Methods and analysis This study is a multicentre, prospective, open-label, RCT that investigates the antireflux effect of LPG-DFT compared with laparoscopic total gastrectomy with Roux-en-Y (LTG-RY) reconstruction for proximal early gastric cancer. A total of 216 eligible patients will be randomly assigned to the LPG-DFT group or the LTG-RY group at a 1:1 ratio using a central, dynamic and stratified block randomisation method, if inclusion criteria are met. General and clinical data will be collected when the patient is enrolled in the study and keep pace with the patient at each stage of his medical and follow-up pathway. The primary endpoint is the proportion of patients with reflux esophagitis (Los Angeles Grade B or more) within 12 months postoperatively. The secondary endpoints included intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, postoperative quality of life, postoperative nutrition status, morbidity and mortality rate, and oncological outcomes (3-year overall survival (OS), 3-year disease-free survival (DFS), 5-year DFS and 5-year OS).Ethics and dissemination The protocol is approved by the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ethics committee (registration number: SYSKY-2022-276-02) on 28 September 2022.We will report the positive as well as negative findings in international peer-reviewed journals.Trial registration number NCT05890339.

ABSTRACT Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage, Myoviridae sp., and Synechococcus phage, showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD.IMPORTANCEPrevious studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD.

ObjectiveWe aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).MethodsMDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes.ResultsOur findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC.ConclusionMDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

A comprehensive analysis of the characteristics of vacuum evaporation and condensation of pure silver is crucial for advancing vacuum separation and purification technology for crude silver. This study analyzes the vacuum evaporation and condensation thermodynamics and evaporation kinetics of pure silver. The results reveal a substantial increase in the saturated vapor pressure and theoretical maximum evaporation rate of pure silver with increasing temperature. When the temperature is in the range of 1373 ∼ 1773 K and the pressure is in the range of 0.1 ∼ 10 Pa, the average molecular free path is between 0.514 ∼ 66.415 cm. Moreover, the mean molecular free path of silver increases with increasing temperature and decreasing pressure. Besides, the silver triple point occurs at a temperature of 1234.78 K and a pressure of 0.343 Pa. The average evaporation rate of pure silver demonstrates a linear relationship with temperature, and the relationship with pressure conforms to the Logistic model. Notably, the vacuum evaporation of pure silver is a first-order reaction. Furthermore, in this study, the kinetic equation of vacuum evaporation of pure silver is established. In the temperature range of 1473–1673 K, the gas phase mass transfer is the rate-controlling step rather than the mass transfer in the gas phase boundary layer. As the temperature increases, the rate-controlling step gradually changes into gas relative flow mass transfer and gas-liquid interface evaporation mass transfer.

Abstract Genetic variants can influence complex traits by altering gene expression through changes to regulatory elements. However, the genetic variants that affect the activity of regulatory elements in pigs are largely unknown, and the extent to which these variants influence gene expression and contribute to the understanding of complex phenotypes remains unclear. Here, we annotate 90,991 high-quality regulatory elements using acetylation of histone H3 on lysine 27 (H3K27ac) ChIP-seq of 292 pig livers. Combined with genome resequencing and RNA-seq data, we identify 28,425 H3K27ac quantitative trait loci (acQTLs) and 12,250 expression quantitative trait loci (eQTLs). Through the allelic imbalance analysis, we validate two causative acQTL variants in independent datasets. We observe substantial sharing of genetic controls between gene expression and H3K27ac, particularly within promoters. We infer that 46% of H3K27ac exhibit a concomitant rather than causative relationship with gene expression. By integrating GWAS, eQTLs, acQTLs, and transcription factor binding prediction, we further demonstrate their application, through metabolites dulcitol, phosphatidylcholine (PC) (16:0/16:0) and published phenotypes, in identifying likely causal variants and genes, and discovering sub-threshold GWAS loci. We provide insight into the relationship between regulatory elements and gene expression, and the genetic foundation for dissecting the molecular mechanism of phenotypes.

Cu–Al2O3/Cu laminated dual heterogeneous microstructure composites with alternating coarse/fine grain distributions were prepared using a combination of accumulative roll bonding and annealing processes. The average layer thickness of the Al2O3/Cu layers is 2.1 μm and that of the Cu layer is 4.2 μm, and meanwhile, the average grain size of the Al2O3/Cu layers and Cu layers are 0.25 μm, 2.3 μm respectively. The strength of Al2O3/Cu layer is higher than that of the Cu layer because of the additional dispersion strengthening and the stronger grain boundary strengthening. Owing to significant differences in the structural and mechanical properties of the layers in this material, geometrically necessary dislocations accumulated at the interface during the tensile process; this resulted in significant heterogeneous deformation-induced strengthening, which yielded a laminated composite with a tensile strength of 413 MPa, tensile ductility of 27%, and excellent overall performance. This work provides a new design strategy for the preparation of high-strength high-ductility materials.

Abstract Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy—both of which contribute to cardiac atrophy and failure after doxorubicin treatment.