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Abstract Background The Inflammatory Load Index (IBI) and Body Roundness Index (BRI) were employed to evaluate the systemic inflammatory status and body fat. This study aims to elucidate the association between IBI and the prevalence of gallstones, as well as to analyze the mediating role of BRI in this association. Methods Data from the National Health and Nutrition Examination Survey (NHANES) (2017–2020) were utilized in our cross-sectional study. A total of 2598 participants aged ≥ 20 years were enrolled. The Boruta algorithm, a supervised classification feature selection method, is leveraged to identify the confounding variables most strongly associated with the prevalence of gallstones. Weighted multivariate logistic regression, restricted cubic splines (RCS), and subgroup analyses were employed to investigate the association between IBI and gallstones, assess the presence of a linear association, and evaluate the effect of IBI on gallstone risk across different populations. Finally, the mediating effect of BRI was examined. Results In the fully adjusted model, when IBI was in the highest tertile, each unit increase in IBI (corresponding to an increase of 1 in the natural logarithm of IBI) was linked to a 110.8% higher prevalence of gallstones (OR = 2.108, 95% CI: 1.109–4.005; P = 0.028). The odds ratio for gallstones increased with higher IBI levels across unadjusted, partially adjusted, and fully adjusted models (P for trend

Background: Intervertebral disc degeneration (IVDD) is one of the important causes of lower back pain, seriously affecting people's health and quality of life. This research employs single-cell analysis to identify the specific cellular subtypes and key regulatory genes associated with IVDD. Methods: We analyzed the single-cell data and screened cells that closely associated with the development of IVDD. The differential expression of feature genes between IVDD and control groups was analyzed. Additionally, drugs and regulatory transcription factors that interact with feature genes were predicted and clinically validated by reverse transcription quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). Results: Our study identified the Chond2 cell subtype associated with IVDD and selected four feature genes influencing the development of IVDD, namely IGFBP3, ACAN, VAPA and TMEM45A, through the high-dimensional weighted gene co-expression network analysis (hdWGCNA) analysis, least absolute shrinkage and selection operator (LASSO), and random forest (RF). Besides, compared to the MDD group, IGFBP3 and TMEM45A were significantly upregulated in the SDD group, while ACAN and VAPA showed no significant difference between the two groups. ELISA testing revealed a positive correlation between IGFBP3 concentration and the grading of IVDD. Furthermore, Celecoxib may be used to treat IVDD by inhibiting IGFBP3. Conclusion: Our study identified the Chond2 cell subtype associated with IVDD and selected four feature genes influencing the development of IVDD, namely IGFBP3, ACAN, VAPA and TMEM45A. Our findings establish a robust theoretical foundation for the clinical diagnosis and treatment of IVDD patients.

Abstract Limited by the adsorption and diffusion rate of water molecules, traditional humidity sensors, such as those based on polymer electrolytes, porous ceramics, and metal oxides, typically have long response times, which hinder their application in monitoring transient humidity changes. Here we present an ultrafast humidity sensor with a millisecond-level response. The sensor is prepared by assembling monolayer graphene oxide quantum dots on silica microspheres using a simple electrostatic self-assembly technique. Benefiting from the joint action of the micro spheres and the ultrathin humidity-sensitive film, it displays the fastest response time (2.76 ms) and recovery time (12.4 ms) among electronic humidity sensors. With the ultrafast response of the sensor, we revealed the correlation between humidity changes in speech airflow and speech activities, demonstrated the noise immunity of humidity speech activity detection, confirmed the humidity shock caused by explosions, realized ultrahigh frequency respiratory monitoring, and verified the effect of humidity-triggering in the non-invasive ventilator. This ultrafast humidity sensor has broad application prospects in monitoring transient humidity changes.

Abstract Background Monoacylglycerol lipase (MAGL) belongs to the serine hydrolase family; it catalyzes MAG to produce glycerol and free fatty acids (FFAs), which is the final step in triacylglycerol (TAG) hydrolysis. The effects of MAGL on comprehensive lipid metabolism and plant growth and development have not been elucidated, especially in Arachis hypogaea, an important oil crop. Results Herein, AhMAGL3b encoding a protein with both hydrolase and acyltransferase regions, a member of MAGL gene family, was cloned and overexpressed in Arabidopsis thaliana. A total of 9 homozygous T3 generation transgenic lines were obtained. Compared with wild type (WT), overexpression (OE) of AhMAGL3b had no obvious growth inhibition by investigation of agronomic traits, including growth and photosynthetic parameters. The leaf fatty acid (FA) content was increased by 12.1–27.4% in AhMAGL3b-OE lines, while seed oil content was decreased by 10.7–17.3%. Furthermore, the overexpression of AhMAGL3b resulted in higher soluble sugar and starch content, and lower total soluble protein content in both leaves and seeds. Additionally, during seed germination, AhMAGL3b-OE seeds were more dormant than that of WT and the sensitivity to abscisic acid (ABA) treatment was decreased. Conclusions Taken together, our results indicate that AhMAGL3b is involved in homeostasis among carbohydrates, lipids and protein in A. hypogaea.

Abstract Liquid biopsies have the potential to revolutionize cancer care through non-invasive early detection of tumors. Developing a robust liquid biopsy test requires collecting high-dimensional data from a large number of blood samples across heterogeneous groups of patients. We propose that the generative capability of variational auto-encoders enables learning a robust and generalizable signature of blood-based biomarkers. In this study, we analyze orphan non-coding RNAs (oncRNAs) from serum samples of 1050 individuals diagnosed with non-small cell lung cancer (NSCLC) at various stages, as well as sex-, age-, and BMI-matched controls. We demonstrate that our multi-task generative AI model, Orion, surpasses commonly used methods in both overall performance and generalizability to held-out datasets. Orion achieves an overall sensitivity of 94% (95% CI: 87%–98%) at 87% (95% CI: 81%–93%) specificity for cancer detection across all stages, outperforming the sensitivity of other methods on held-out validation datasets by more than ~ 30%.

Abstract Objective To investigate whether body mass index (BMI) affects the accuracy of vertebral bone quality (VBQ) in determining bone mineral density (BMD) in patients undergoing lumbar fusion surgery. Methods In this retrospective study, patients with preoperative noncontrast T1-weighted MRI were included. Restricted Cubic Spline (RCS) was employed to explore the nonlinear relationship between BMI and VBQ. Then patients were stratified according to the threshold of BMI. Pearson correlation analysis and linear regression were used to analyze the correlation between VBQ and the BMD in different groups. Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was used to assess diagnostic efficacy according to BMI. Results A total of 328 patients (201 female and 127 male patients) with a mean age of 68.3 ± 3.3 years were included in the study. Significant nonlinear relationship was observed given the results of RCS. In patients with BMI

Abstract Background Manipulation under anesthesia (MUA) has been recommended for refractory arthrofibrosis after anterior cruciate ligament (ACL) reconstruction. However, the effectiveness of MUA to restore normal kinematics of the arthrofibrotic knee is still unclear. The objective of this study was to evaluate tibiofemoral and patellofemoral kinematics in six degrees-of-freedom (6DOF) in patients with arthrofibrosis before and after MUA. Methods Computed tomography and dual fluoroscopic imaging system were used to assess in vivo knee kinematics. Ten patients (6 women and 4 men; 32.6 ± 6.5y, 168.4 ± 7.8 cm, 61.8 ± 13.2 kg) were included in this study. The tibiofemoral and patellofemoral kinematics in 6DOF were collected before and one year after MUA. A simple analysis of variance was used to evaluate kinematic data of preoperative arthrofibrotic knee, postoperative arthrofibrotic knee, and the contralateral knee. Results The patella in the postoperative arthrofibrotic knee shifted significantly more inferiorly compared to the preoperative knee at 45° (P = 0.010), 60° (P = 0.008), and 75° (P = 0.049) of flexion. The patellar flexion in the postoperative arthrofibrotic knee significantly increased at 45° (P = 0.048), 60° (P = 0.037), and 75° (P = 0.006) of flexion compared to the preoperative arthrofibrotic knee. The patellar tilt was significantly decreased at 60° (P = 0.006) and at 75° (P = 0.037) of knee flexion in the postoperative arthrofibrotic knee compared to the contralateral knee. MUA significantly increased tibial internal rotation angle in the arthrofibrotic knee at 45° (P = 0.047), at 60° (P = 0.033), and at 75° (P = 0.021) of knee flexion. Conclusions MUA could restore normal patellar inferior shift, flexion, and tibial rotation compared to the contralateral side. However, the MUA could not restore normal patellar tilt of the arthrofibrotic knee. This indicated that improvement of patellar tilt should be emphasized in postoperative rehabilitation.

Abstract Phenology reflects the life cycle of vegetation, crucial for monitoring global vegetation diversity, ecosystem stability, and agricultural security. However, there is currently no dataset related to phenology. The 24 solar terms (24STs), based on the Sun's annual motion, reflect the changing seasons, temperature fluctuations, and phenological phenomena. They serve as a vital means to characterize vegetation phenology. This study generate a global Normalized Difference Vegetation Index (NDVI) product based on 24STs using Moderate Resolution Imaging Spectroradiometer (MODIS) on the Google Earth Engine (GEE). The 24STs NDVI dataset adopted the maximum value compositing (MVC) to process the NDVI values between two adjacent 24STs. The product has a spatial resolution of 250 m, covering the period from 2001 to 2022. Comparing with the MOD13Q1, good spatiotemporal consistency between the two datasets was observed, confirming the reliability of the 24STs product. However, the 24STs product holds distinct phenological meanings. This product introduces, for the first time, a vegetation index dataset based on the 24STs, enriching the vegetation index dataset and facilitating further research on phenology.

Abstract As the main equipment of coal mining production, the anomaly detection of shearer is important to ensure production efficiency and coal mine safety. One key challenge lies in the limited or even absence of labeled monitoring data for the equipment, coupled with the high costs associated with manual annotation. Another challenge stems from the complex structure of the mining machines, making it difficult to reflect the overall operational state through local anomaly detection. Consequently, the application of decoupled local anomaly detection for mining machines in practical production remains challenging. This paper presents an unsupervised learning-based method for detecting anomalies in shearer. The method includes a module for constructing a Multi-scale Correlation Matrix (MSCM) of mining machine operating conditions, as well as the CNN-ConvLSTM Autoencoder (C-CLA) network. The module for constructing an MSCM enhances the representation of interrelationships between various features of the equipment from different perspectives using multiple correlation analysis methods. The C-CLA network integrates convolutional and convolutional recurrent neural networks, with the convolutional structure extracting local spatial features and the ConvLSTM structure further capturing information from different time scales and feature scales, thereby enhancing the model’s perceptual capabilities towards changes in equipment status. Finally, shearer anomaly detection is achieved through the analysis of reconstructed residual matrices. The rationality and practicality of the proposed method have been validated on our dataset, and the model’s generalization capability has been verified through repeated experiments in similar scenarios. However, due to variations in the working environment of different mining faces and differences in equipment models, implementing detection on other mining faces often requires retraining the model with new data. Furthermore, we compared our method with other anomaly detection techniques, and our detection efficiency was superior by approximately 3%. This method effectively detects anomalies in the shearer.

Abstract Offset responses are traditionally viewed as indicators of sound cessation. Here, we investigate offset responses to auditory click trains, examining how they are modulated by inter-click intervals (ICIs) and train duration. Using extracellular recordings and electrocorticography (ECoG) in non-human primates, alongside electroencephalography (EEG) in humans, we show that offset responses are significantly influenced by both ICI and train length, thereby establishing them as markers of temporal integration. We introduce the concept of the ‘Neuronal Integrative Window’ (NIW), defined as the temporal span during which neurons integrate stimuli to produce or modulate the temporal integration signal. Our data reveal that on the neuronal level, the auditory cortex (AC) exhibits a more expansive NIW than the medial geniculate body (MGB), integrating stimuli over longer durations and showing a preference for larger ICIs. Furthermore, our results indicate that offset responses could serve as potential biomarkers for neurological and psychiatric conditions, highlighted by their sensitivity to pharmacological modulation with ketamine. This study advances our understanding of auditory temporal processing and proposes a novel approach for assessing and monitoring brain health.

Conventionally, smell has been regarded as a relatively ineffable percept and concept. However, the personal experience of using the olfactory Chinese word chòu (臭, 'smelly') makes me think that the word is not so ineffable in China as people often use it daily. To verify the hypothesis that the Chinese character chòu (臭) has distinctive figurative sense and collocation patterns compared with English terms like foul, smelly, or stinking, the study used corpus-linguistic data to identify the salience, frequency, and collocation of olfactory words in Chinese and English. The study shows that the psychological similarity between bad smell and negative mental states is very salient in both languages. Nevertheless, the construal of the subjective feelings conveyed through these olfactory words is subject to the specific context and the speaker's intention.

Catechins, the most important bioactive components in tea plants (Camellia sinensis), are influenced by the growth environment. To identify and optimize the key meteorological factors affecting catechin accumulation, we investigated the relationship between meteorological factors and tea plant catechin biosynthesis across three growing seasons at 10 locations. Rainfall, average temperature, and effective accumulated temperature (EAT) were identified as key drivers regulating catechin accumulation via the responsive expression of key structural genes CsCHS1, CsANR, and CsSCPL. Optimal meteorological conditions for enhancing total esterified catechins (TEC) and total non-esterified catechins (TNEC) were determined using LINGO software, although the optimal conditions for these two groups were contrasting. Hot and rainy environments promote the biosynthesis of EGCG, ECG, and TEC through CsPAL and CsSCPL, while reduced rainfall and EAT promote the accumulation of C, EGC, and TNEC. This study reveals the differential effects of meteorological factors on catechin accumulation and obtains optimal meteorological conditions for promoting catechin accumulation. These results provide guidance for improving catechin accumulation and tea cultivation management.

The inferior colliculus (IC) has traditionally been regarded as an important relay in the auditory pathway, primarily involved in relaying auditory information from the brainstem to the thalamus. However, this study uncovers the multifaceted role of the IC in bridging auditory processing, sensory prediction, and reward prediction. Through extracellular recordings in monkeys engaged in a sound duration-based deviation detection task, we observed a 'climbing effect' in neuronal firing rates, indicative of an enhanced response over sound sequences linked to sensory prediction rather than reward anticipation. Moreover, our findings demonstrate reward prediction errors within the IC, highlighting its complex integration in auditory and reward processing. Further analysis revealed a direct correlation between IC neuronal activity and behavioral choices, suggesting its involvement in decision-making processes. This research highlights a more complex role for the IC than traditionally understood, showcasing its integral role in cognitive and sensory processing and emphasizing its importance in integrated brain functions.

We reported the pseudoprogression in an elderly patient with advanced gastric cancer after chimeric antigen receptor (CAR)-T cell therapy. The hepatic metastases enlarged 1 month after CAR-T cell infusion and then shrunk the next month as seen through computed tomography scanning. Based on a comprehensive evaluation that includes imaging, pathology, serum tumor markers, and clinical symptoms, we arrived at a diagnosis of pseudoprogression after CAR-T cell therapy, which has not been reported in previous studies. In this report, we provide detailed descriptions of the patient’s clinical presentation, imaging findings, treatment process, and follow-up outcomes. We believe that this case holds important implications for CAR-T cell therapy research and offers valuable insights for clinical practice.

AIM: To determine whether etomidate (ET) has a protective effect on retinal ganglion cells (RGCs) injured with hydrogen peroxide (H2O2) and to explore the potential mechanism underlying the antioxidative stress effect of ET. METHODS: Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1. An injury model of H2O2-induced RGCs oxidative stress was established in vitro. Cells were pretreated with different concentrations of ET (1, 5, and 10 μmol/L) for 4h, followed by further exposure to H2O2 at 1000 μmol/L. Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12, 24, and 48h after H2O2 stimulation. The levels of nitric oxide, malondialdehyde, and glutathione in culture media were measured at these time points. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12, 24, and 48h after H2O2 stimulation and in the retina at 12h after optic nerve transection (ONT). RESULTS: The applications of 5 and 10 μmol/L of ET significantly increased the viability of RGCs. Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs at 12, 24 and 48h after H2O2 stimulation, as well as in ET-treated retinas at 12h after ONT. Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein, along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo. CONCLUSION: ET is a neuroprotective agent in primary cultured RGCs injured by H2O2. The effect of ET is dose-dependent with the greatest effect being at 10 μmol/L. ET plays an antioxidant role by inhibiting iNOS, up-regulating Nrf2/HO-1, decreasing the production of acrolein, and increasing the scavenge of acrolein.

Abstract Single‐image dehazing is a highly challenging ill‐posed task in the field of computer vision. To address this, a new image dehazing model with feature attention, named feature attention gated context aggregation network (FAGCA‐Net), is proposed to tackle the issues of incomplete or over‐dehazing caused by the original model's inability to handle non‐uniform haze density distributions. A feature attention module that combines channel attention and spatial attention is introduced. Additionally, the authors propose a new extended attention convolutional block, which not only addresses the grid artefacts caused by the extended convolution but also provides added flexibility in handling different types of feature information. At the same time, in addition to the input image itself, incorporating the dark channel and edge channel of the image as the final input of the model is helpful for the model learning process. To demonstrate the robustness of the new model, it is applied to two completely different dehazing datasets, and it achieves significant dehazing performance improvement over the original model. Finally, to verify the effectiveness of the model in practical production processes, the authors apply it as an image preprocessing step to a set of UAV (Unmanned Aerial Vehicle) images of foreign objects. The result shows that the UAV images after being processed by FAGCA‐Net for haze removal have a better impact on subsequent usage.

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1− T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1− T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.

Many different cell types and complex molecular pathways are involved in intervertebral disc degeneration (IDD). We used a multi-omics approach combining single-cell RNA sequencing (scRNA-seq), differential gene expression analysis, and Mendelian randomization (MR) to clarify the underlying genetic architecture of IDD. We identified 1,164 differentially expressed genes (DEGs) across four important cell types associated with IDD using publicly available single-cell datasets. A thorough gene network analysis identified 122 genes that may be connected to programmed cell death (PCD), a crucial route in the etiology of IDD. SLC40A1, PTGS2, and GABARAPL1 have been identified as noteworthy regulatory genes that may impede the advancement of IDD. Furthermore, distinct cellular subpopulations and dynamic gene expression patterns were revealed by functional enrichment analysis and pseudo-temporal ordering of chondrocytes. Our results highlight the therapeutic potential of GABARAPL1, PTGS2, and SLC40A1 targeting in the treatment of IDD.

Identity-based threshold signature (IDTHS) allows a threshold number of signers to generate signatures to improve the deterministic wallet in the blockchain. However, the IDTHS scheme cannot determine the identity of malicious signers in case of misinformation. To solve this challenge, we propose an identity-based threshold (multi) signature with private accountability (for short AIDTHS) for privacy-preserving blockchain. From the public perspective, AIDTHS is completely private and no user knows who participated in generating the signature. At the same time, when there is a problem with the transaction, a trace entity can trace and be accountable to the signers. We formally define the syntax and security model of AIDTHS. To address the issue of identifying malicious signers, we improve upon traditional identity-based threshold signatures by incorporating zero-knowledge proofs as part of the signature and leveraging a tracer holding tracing keys to identify all signers. Additionally, to protect the privacy of signers, the signature is no longer achievable by anyone, which requires a combiner holding the keys to produce a valid signature. We give a concrete construction of AIDTHS and prove its security. Finally, we implement the AIDTHS scheme and compare it with existing schemes. The key distribution algorithm of AIDTHS takes 13.04 ms and the signature algorithm takes 34.60 μs. The verification algorithm takes 1 s, which is one-third of the time the TAPS scheme uses.

Summary: Background: Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction. Methods: Using data from the Health and Retirement Study (HRS) [2008–2020] and the English Longitudinal Study of Ageing (ELSA) [2004–2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact. Findings: A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72–3.69 in the HRS; 1.43, 1.09–1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%–14.6%) and 2.7% (0.5%–14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40–5.38 in the HRS; 2.02, 1.25–3.27 in the ELSA) and accelerated rate of global cognitive decline (β = −0.058 SD/year; 95% CI: −0.073, −0.043 in the HRS; β = −0.049 SD/year; 95% CI: −0.063, −0.035 in the ELSA). Interpretation: Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults. Funding: This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Objects: To evaluate the association of direct oral anticoagulants (DOACs) and warfarin with dementia incidence in atrial fibrillation (AF) patients. Methods: Relevant studies were retrieved in databases including Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Meta-analysis was then conducted using Stata 12.0 software. Results: A total of 9 studies involving 447,644 AF patients were included. The results indicated that AF patients treated with DOACs had a lower incidence of dementia compared to those treated with warfarin (RR: 0.692, 95 % CI: 0.603–0.793, P = 0.000), This trend was observed in both age groups,

Abstract Background We aimed to explore the association between visit‐to‐visit systolic blood pressure variability (BPV) and cognitive function in individuals with type 2 diabetes. Methods We performed a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD‐MIND) substudy. A total of 2867 diabetes patients with ≥3 BP measurements between the 4‐ and 20‐month visits were included. Visit‐to‐visit systolic BPV was calculated. Cognitive decline was defined as a Mini‐Mental State Exam (MMSE), Digit Symbol Substitution Test (DSST), or Rey Auditory Verbal Learning Test (RAVLT) score greater than 1 standard deviation (SD) below the baseline mean, or a Stroop test score more than 1 SD above the baseline mean. The associations of systolic BPV with risks of cognitive decline were examined using Cox proportional hazards models, and with changes in brain magnetic resonance imaging parameters were evaluated using mixed models. Results The risk of cognitive decline defined by the DSST score (but not by other scores) increased significantly with systolic BPV quartiles (p for trend = 0.008), and there was a 55% increased risk for BPV quartile 4 versus quartile 1 (hazard ratio = 1.55, 95% confidence interval 1.10–2.19). Furthermore, a positive correlation was observed between systolic BPV and change in white matter lesion volume (β = 0.07, 95% CI 0.01–0.13). Conclusions A greater visit‐to‐visit systolic BPV was significantly associated with an increased risk of cognitive decline measured by DSST and an increase in white matter lesion volume in patients with type 2 diabetes.

Post-weaning diarrhea (PWD) is a globally significant threat to the swine industry. Historically, antibiotics as well as high doses of zinc oxide and copper sulfate have been commonly used to control PWD. However, the development of bacterial resistance and environmental pollution have created an interest in alternative strategies. In recent years, the research surrounding these alternative strategies and the mechanisms of piglet diarrhea has been continually updated. Mechanically, diarrhea in piglets is a result of an imbalance in intestinal fluid and electrolyte absorption and secretion. In general, enterotoxigenic Escherichia coli (ETEC) and diarrheal viruses are known to cause an imbalance in the absorption and secretion of intestinal fluids and electrolytes in piglets, resulting in diarrhea when Cl− secretion-driven fluid secretion surpasses absorptive capacity. From a perspective of feedstuffs, factors that contribute to imbalances in fluid absorption and secretion in the intestines of weaned piglets include high levels of crude protein (CP), stimulation by certain antigenic proteins, high acid-binding capacity (ABC), and contamination with deoxynivalenol (DON) in the diet. In response, efforts to reduce CP levels in diets, select feedstuffs with lower ABC values, and process feedstuffs using physical, chemical, and biological approaches are important strategies for alleviating PWD in piglets. Additionally, the diet supplementation with additives such as vitamins and natural products can also play a role in reducing the diarrhea incidence in weaned piglets. Here, we examine the mechanisms of absorption and secretion of intestinal fluids and electrolytes in piglets, summarize nutritional strategies to control PWD in piglets from the perspective of feeds, and provide new insights towards future research directions.

The intestinal architecture of piglets is vulnerable to disruption during weaning transition and leads to diarrhea, frequently accompanied by inflammation and metabolic disturbances (including amino acid metabolism). Tryptophan (Trp) plays an essential role in orchestrating intestinal immune tolerance through its metabolism via the kynurenine, 5-hydroxytryptamine, or indole pathways, which could be dictated by the gut microbiota either directly or indirectly. Emerging evidence suggests a strong association between piglet diarrhea and Trp metabolism. Here we aim to summarize the intricate balance of microbiota–host crosstalk by analyzing alterations in both the host and microbial pathways of Trp and discuss how Trp metabolism may affect piglet diarrhea. Overall, this review could provide valuable insights to explore effective strategies for managing piglet diarrhea and the related challenges.

Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Abstract Stark effect, the electric-field analogue of magnetic Zeeman effect, is one of the celebrated phenomena in modern physics and appealing for emergent applications in electronics, optoelectronics, as well as quantum technologies. While in condensed matter it has prospered only for excitons, whether other collective excitations can display Stark effect remains elusive. Here, we report the observation of phonon Stark effect in a two-dimensional quantum system of bilayer 2H-MoS2. The longitudinal acoustic phonon red-shifts linearly with applied electric fields and can be tuned over ~1 THz, evidencing giant Stark effect of phonons. Together with many-body ab initio calculations, we uncover that the observed phonon Stark effect originates fundamentally from the strong coupling between phonons and interlayer excitons (IXs). In addition, IX-mediated electro-phonon intensity modulation up to ~1200% is discovered for infrared-active phonon A 2u. Our results unveil the exotic phonon Stark effect and effective phonon engineering by IX-mediated mechanism, promising for a plethora of exciting many-body physics and potential technological innovations.

Abstract Background There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). Methods Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran’s Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy. Result We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses. Conclusion Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.

Abstract Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning algorithm extends the depth-of-field, allowing rapid acquisition of in-focus images from large areas of tissue even when the tissue surface is highly irregular. Finally, a semi-supervised generative adversarial network virtually stains DeepDOF-SE fluorescence images with hematoxylin-and-eosin appearance, facilitating image interpretation by pathologists without significant additional training. We developed the DeepDOF-SE platform using a data-driven approach and validated its performance by imaging surgical resections of suspected oral tumors. Our results show that DeepDOF-SE provides histological information of diagnostic importance, offering a rapid and affordable slide-free histology platform for intraoperative tumor margin assessment and in low-resource settings.

RNA N6-methyladenosine (m6A) methylation is the most abundant and conserved RNA modification in eukaryotes. It participates in the regulation of RNA metabolism and various pathophysiological processes. Non-coding RNAs (ncRNAs) are defined as small or long transcripts which do not encode proteins and display numerous biological regulatory functions. Similar to mRNAs, m6A deposition is observed in ncRNAs. Studying RNA m6A modifications on ncRNAs is of great importance specifically to deepen our understanding of their biological roles and clinical implications. In this review, we summarized the recent research findings regarding the mutual regulation between RNA m6A modification and ncRNAs (with a specific focus on microRNAs, long non-coding RNAs, and circular RNAs) and their functions. We also discussed the challenges of m6A-containing ncRNAs and RNA m6A as therapeutic targets in human diseases and their future perspective in translational roles.

Summary: The neural mechanisms of novelty detection, especially in relation to behavior, are currently poorly understood. Here, we present a protocol for recording neuronal activity in macaque auditory cortex during novelty detection tasks. We describe steps for behavioral training, surgical headpost implantation, MRI-based electrode targeting, and electrophysiological recording. These steps allow direct assessment of the correlation between novelty detection behavior and neuronal activity.For complete details on the use and execution of this protocol, please refer to Gong et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Purpose To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second‐line monotherapy for treating small‐cell lung cancer (SCLC) patients. Methods According to the “3 + 3” dose‐escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression‐free survival (PFS), overall survival (OS), median progression‐free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. Results This study included 29 patients with stage III–IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose‐limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. Conclusion JK1201I exhibits promising efficacy and relatively low toxicities as a second‐line monotherapy for SCLC, warranting further large‐scale clinical studies to evaluate its efficacy in greater detail.

Background: Recent research highlights the importance of muscular strength as a key factor in physical fitness, a strong indicator of overall mortality risk, and a vital target for preventing chronic diseases. This study used a proteome-wide Mendelian randomization analysis plus colocalization analysis for low hand grip strength to explore potential therapeutic targets for muscle weakness. Methods: We conducted two two-sample Mendelian randomization analyses from four cohorts to identify and validate the causal relationship between plasma proteins and low grip strength. We also employed bidirectional Mendelian randomization analysis with Steiger filtering, Bayesian co-localization, and phenotype scanning to detect reverse causality, thereby consolidating our Mendelian randomization findings. Downstream analyses were also undertaken of identified proteins, including knockout models, enrichment analyses, and protein-protein interaction networks. Finally, we assessed the druggability of the identified proteins. Results: At Bonferroni significance (P

Background and purpose: Remimazolam is a newly developed benzodiazepine drug with water-soluble, esterase degradation, and ultra-short-acting properties. The dose for general anesthesia induction in obese patients was not known. This study aimed to determine the optimal dose of remimazolam in combination with sufentanil for the induction of general anesthesia in obese patients.Methods: It was a prospective observational study. We recruited 46 patients scheduled for bariatric surgery from October 2022 to December 2023. One patient refused to provide informed consent, and six patients were receiving psychotropic medication. Thirty-nine patients were enrolled. The Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale was used to assess the patient’s response. The dose of sufentanil was 0.5 µg/kg (lean body weight [LBW]). The initial dose of remimazolam was 0.3 mg/kg (LBW). The dose of remimazolam was modified using the up-and-down allocation technique. Successful sedation (negative group) was characterized by achieving a MOAA/S score ≤ 1 within 3 min of commencing remimazolam infusion. If negative, the next patient received a low-level dose at a ratio of 0.9. Failed sedation (positive group) was defined as a MOAA/S score of >1 within 3 min of commencing remimazolam infusion. The patients in the positive group received propofol 0.5 mg/kg as a remedial measure, and the next dose was increased to a higher level. The primary outcome was to determine the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam in combination with sufentanil 0.5 µg/kg for induction in obese patients. The secondary outcome was to determine the occurrence of adverse effects such as hypotension, hypertension, and intraoperative awareness.Results: The ED50 and ED95 values of remimazolam (LBW) combined with sufentanil (0.5 µg/kg) (LBW) were 0.115 mg/kg (95% CI: 0.072–0.137) and 0.179 mg/kg (95% CI: 0.150–0.434), respectively, and the time of loss of consciousness in the negative group was 120.13 ± 25.03 s. The cardiovascular system was stable during the induction period. The incidence of post operative nausea and vomiting (PONV) was 38.5% in 39 patients. Respiratory depression, allergic reaction, intraoperative awareness, and delayed emergence were not observed in any patient.Conclusion: Remimazolam combined with sufentanil (0.5 µg/kg) (LBW) can be effectively used for general anesthesia induction in obese patients. The ED50 and ED95 values of remimazolam (LBW) were 0.115 mg/kg and 0.179 mg/kg, respectively.Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200065602.

Abstract Poly(acrylic acid) (PAAc) hydrogels are essential functional materials. However, their mechanical properties do not meet the required standards. In this study, a one‐pot method is employed to prepare cellulose‐reinforced PAAc hydrogels by dissolving allyl cellulose (AC) in acrylic acid (AAc) solutions. Fourier transform infrared (FTIR), solid‐state 13C nuclear magnetic resonance (NMR), and thermogravimetric (TG) analysis are used to demonstrate that the incorporation of AC results in the formation of covalent and hydrogen bonds, which contribute to the crosslink network of the PAAc hydrogels. Significantly, by modifying the ratio of AC to AAc in the pre‐polymerization solution, the prepared AC–PAAc hydrogels exhibit a transition from transparent to opaque. This suggests that phase separation is induced by hydrogen bonding. The occurrence of phase separation is verified by observing the hydrogel microstructures using scanning electron microscopy. Phase separation leads to enhanced polymer–polymer interactions in the hydrogels, resulting in a maximum fracture stress of 2.34 MPa. The AC–PAAc hydrogels display distinct swelling behavior under various pH conditions. Moreover, they demonstrate differences in transparency and mechanical properties when exposed to dimethyl sulfoxide (DMSO) and water, indicating their responsiveness to solvents. This work demonstrates the great potential of enhancing the mechanical performance and responsiveness of PAAc hydrogels.

Internet Gaming Disorder (IGD) is a behavioural addiction characterised by excessive exposure to addictive stimuli, resulting in reduced sensitivity of the brain's reward system towards everyday rewards. Online game addiction is prevalent among adolescents; however, it remains unclear if there are variations in reward processing patterns among adolescents with online game addiction.We compared differences in sensitivity to two types of rewards between patients with IGD and patients with Recreational Game Use (RGU) using the Monetary Incentive Delay (MID) paradigm and the Social Incentive Delay (SID) paradigm (Experiment 1). Additionally, we used a mixed reward latency paradigm, including both monetary and social rewards, to further explore the processing characteristics of IGD towards a mixture of these two rewards (Experiment 2).There were significant differences in the sensitivity of IGD and RGU to monetary and social rewards. Adolescents with IGD had significantly shorter reaction times to the four mixed rewards compared to RGU, while no significant differences were found between groups regarding sensitivity to specific individual rewards. However, the simultaneous presence of two rewards affected the processing speed and preference of adolescents with IGD.The reward processing characteristics observed in adolescents with online gaming disorder show specificity concerning the type and presentation of rewards, providing a theoretical foundation for diagnosing and treating adolescent online gaming addiction.

Tea pigment, as a natural pigment component in tea, has attracted much attention because of its unique health benefits. In recent years, with the deepening of scientific research, the research on biological activity, extraction technology and application of tea pigment has made remarkable progress. Through systematic bibliometrics analysis, this paper comprehensively combs and evaluates the research status of tea pigment. The propose is to provide valuable reference for future research and application. In this paper, the chemical structure of tea pigment is firstly summarized, and then its diverse biological activities, such as antioxidant, anti-inflammatory and anti-tumor, are deeply discussed, especially its potential application in the treatment of cardiovascular diseases and diabetes. In addition, the application prospect of tea pigment in food coloring, textile dyeing and other industrial fields is also discussed in detail. Through the collection and arrangement of a large number of research literatures, this paper analyzes the development trend, research methods and main achievements of tea pigment research, and pays special attention to the dosage and effect of tea pigment in practical application. These analyses not only contribute to a more comprehensive understanding of the characteristics and functions of tea pigments, but also provide scientific basis for the further development and application of tea pigments.

Abstract This study aimed to investigate the effects of ammonia addition on ethylene counter-flow diffusion flames with different diluents on the fuel or oxidizer side, using kinetic analyses. A special emphasis was put on assessing the coupled chemical effects of NH3 and CO2 on C2H4 combustion chemistry. The chemical effects could be evaluated by comparing fictitious inert NH3 or CO2 with normal active NH3 or CO2. The results revealed that the addition of NH3 decreased the mole fractions and production rates of key soot precursors, such as acetylene, propynyl, and benzene. When CO2 was used as the dilution gas, the coupled chemical effects of NH3 and CO2 were affected by the chemical effects of CO2 to varying degrees. With the oxidizer-side CO2 addition, the coupled chemical effects of NH3 and CO2 reduced the mole fractions of H, O, OH radicals, acetylene, propynyl, and benzene, while the effects differed from the fuel-side CO2 addition. The coupled chemical effects of NH3 and CO2 also promoted the formation of aldehyde contaminants, such as acetaldehyde, to some extent, particularly with CO2 addition on the oxidizer side.

Abstract Monolayer molybdenum disulfide (MoS2), an emergent two-dimensional (2D) semiconductor, holds great promise for transcending the fundamental limits of silicon electronics and continue the downscaling of field-effect transistors. To realize its full potential and high-end applications, controlled synthesis of wafer-scale monolayer MoS2 single crystals on general commercial substrates is highly desired yet challenging. Here, we demonstrate the successful epitaxial growth of 2-inch single-crystal MoS2 monolayers on industry-compatible substrates of c-plane sapphire by engineering the formation of a specific interfacial reconstructed layer through the S/MoO3 precursor ratio control. The unidirectional alignment and seamless stitching of MoS2 domains across the entire wafer are demonstrated through cross-dimensional characterizations ranging from atomic- to centimeter-scale. The epitaxial monolayer MoS2 single crystal shows good wafer-scale uniformity and state-of-the-art quality, as evidenced from the ~100% phonon circular dichroism, exciton valley polarization of ~70%, room-temperature mobility of ~140 cm2v−1s−1, and on/off ratio of ~109. Our work provides a simple strategy to produce wafer-scale single-crystal 2D semiconductors on commercial insulator substrates, paving the way towards the further extension of Moore’s law and industrial applications of 2D electronic circuits.

Abstract Background Emerging data point to the critical role of snoRNA in the emergence of different types of cancer, but scarcely in breast cancer (BC). This study aimed to clarify the differential expressions and potential diagnostic value of SNORD16, SNORA73B, SCARNA4, and SNORD49B in BC. Methods We screened differential snoRNAs in BC tissues and adjacent tissues through SNORic datasets, and then we further verified them in the plasma of BC patients and healthy volunteers by quantitative polymerase chain reaction (qPCR). Results These four snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were considerably more abundant in cancerous tissues than in neighboring tissues in the TCGA database. Their plasma levels were also higher in BC and early-stage BC patients when compared to healthy controls. Furthermore, the ROC curve demonstrated that BC (AUC = 0.7521) and early-stage BC (AUC = 0.7305) might be successfully distinguished from healthy people by SNORD16, SNORA73B, SCARNA4, and SNORD49B. Conclusion Plasma snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were upregulated in BC and early-stage BC and can be used as potential diagnostic markers for BC and early-stage BC.

Objective: Postpartum weight retention (PPWR) is a common problem among women after childbirth. The main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition, including macronutrients, leptin, and adiponectin. Methods: The study included a longitudinal cohort (122 mothers), and a cross-sectional cohort (37 mothers). The human milk, maternal weight, and dietary surveys were collected in the longitudinal cohort at different follow-up time points (1−14 days postpartum, 2−4 months postpartum, 5−7 months postpartum, and 12−17 months postpartum). The maternal body weight was analyzed using the responses in the survey questionnaires. A milk analyzer based on the mid-infrared spectroscopy (MIRS) was used to determine milk composition, and nutrition analysis software evaluated dietary intakes. In the cross-sectional cohort, participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body composition. Maternal body composition was measured by bioelectrical impedance analysis (BIA), while ELISA analyzed leptin and adiponectin in milk and serum. Results: At 5−7 months postpartum, the PPWR of breastfeeding mothers was (2.46 ± 3.59) kg. At 12−17 months postpartum, the PPWR was (0.98 ± 4.06) kg. PPWR was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2−4 months postpartum. In addition, the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in milk. Plasma leptin was positively correlated with the mother's body weight, body mass index (BMI), FAT percentage, and body fat mass, while plasma adiponectin did not correlate with any parameter. The results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or milk. Conclusions: Breastfeeding mothers may retain considerable weight gain one year after delivery. Human milk composition may be related to changes in maternal body weight. Leptin and adiponectin in breast milk and leptin in plasma are associated with the maternal body composition. This study supports the notion that maternal nutritional status may affect offspring health through lactation, and future research should focus on exploring weight management of postpartum mothers.

Abstract Purpose The alterations of RNA profile in tumor-educated platelets (TEPs) have been described as a novel biosource for cancer diagnostics. This study aimed to explore the potential snoRNAs in TEP as biomarkers for diagnostics of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). Methods Platelets were isolated using low-speed centrifugation and subjected to a quantitative polymerase chain reaction (qPCR) for snoRNAs detection. Results Down-regulated SNORD12B and SNORD14E as well as up-regulated SNORA63 were identified in TEP from HBV-related HCC, which could act as diagnostic biomarkers for HBV-related HCC as well as the early disease. Besides, TEP SNORD12B, SNORD14E, and SNORA63 facilitate the diagnostic performance of AFP and achieve favorable diagnostics efficiency for HBV-related HCC when combined with platelet parameters. Conclusions Aberrant expression of SNORD12B, SNORA63, and SNORD14E in TEPs could serve as the novel and non-invasive biomarkers for HBV-related HCC diagnosis.

A high-order variable-step numerical scheme is formulated for the space–time-fractional Cahn–Hilliard equation, employing the variable-step fractional BDF2 formula. The unique solvability and mass conservation at the discretization setting are established. Subject to the constraint of time-step ratios, i.e., 0.4159≤rk≤4.660, a careful analysis based on the discrete gradient structure of the fractional BDF2 formula reveals that the proposed scheme adheres to the energy dissipation law. Remarkably, the modified energy exhibits asymptotic compatibility with that of the classical Cahn–Hilliard equation. Moreover, the modified energy dissipation law of the resulting scheme for the space–time-fractional Cahn–Hilliard equation aligns asymptotically with that of the variable-step BDF2 scheme for its classical counterpart. Finally, a few numerical experiments combined with the adaptive method are presented, which confirm the accuracy and efficiency of the proposed scheme.

This paper presents a novel approach to developing control strategies for mobile robots, specifically the Pegasus, a bionic wheel-legged quadruped robot with unique chassis mechanics that enable four-wheel independent steering and diverse gaits. A multi-agent (MA) reinforcement learning (RL) controller is proposed, treating each leg as an independent agent with the goal of autonomous learning. The framework involves a multi-agent setup to model torso and leg dynamics, incorporating motion guidance optimization signal in the policy training and reward function. By doing so, we address leg schedule patterns for the complex configuration of the Pegasus, the requirement for various gaits, and the design of reward functions for MA-RL agents. Agents were trained using two variations of policy networks based on the framework, and real-world tests show promising results with easy policy transfer from simulation to the actual hardware. The proposed framework models acquired higher rewards and converged faster in training than other variants. Various experiments on the robot deployed framework showed fast response (0.8 s) under disturbance and low linear, angular velocity, and heading error, which was 2.5 cm/s, 0.06 rad/s, and 4°, respectively. Overall, the study demonstrates the feasibility of the proposed MA-RL control framework.

Metallurgical industrial buildings, particularly those over 10 years old, frequently experience increased vibrations in their latticed columns due to prolonged dynamic loads from cranes, affecting both structural safety and usability. To enhance the strength and stiffness of these structures in a cost-effective way, a novel composite latticed column made from concrete-filled steel tubes and corrugated steel plates is proposed. An analytical study on its axial compression behavior has also been conducted. The analytical parameters included the yield strength of steel tube and compressive strength of concrete, the waveform of corrugated steel plate, as well as the thickness, yield strength, and configuration of steel lacing tubes. Results show that compared to specimens with C30 concrete, the bearing capacity and initial axial stiffness of specimens with C50 concrete can increase by 35% and 33%, respectively. Compared with the steel specimen with yield strength of 235 MPa, the peak bearing capacity of the steel specimen with yield strength of 400 MPa can be increased by 28%. Additionally, increasing the wave height reduces the concrete cross section, resulting in a decrease in axial stiffness and ductility. Compared to specimens with horizontal lacing tubes, those with diagonal lacing tubes exhibit increases in ductility and axial stiffness of 33% and 12%, respectively. Therefore, diagonal lacing tubes should be considered for the optimal axial compression behavior of latticed columns. Furthermore, a model for predicting the axial compression bearing capacity of latticed columns with CFST tubes and corrugated steel plates was proposed.

Abstract Introduction Diet selection of grazing livestock is one of the critical factors affecting the diversity and composition of plant communities in grasslands, with consequent impacts for ecosystem functioning. Co‐grazing of multiple livestock species could create additive or complementary effects on plant communities due to diet overlap or differentiation among livestock species. However, there is only limited knowledge about diet overlap and differentiation of co‐occurring livestock species and whether or how these diet characteristics change with grassland degradation. Materials and Methods We experimentally test the diets of two commonly co‐occurring livestock species (cattle and sheep) and the dietary niche partitioning/overlap between them in non‐degraded, moderately and severely degraded grasslands. Results Cattle exhibited broader diet than sheep, and diet overlap between species was lower in non‐degraded grasslands. As grassland degradation increased the availability of annual plants, interspecific niche overlap between cattle and sheep gradually increased, and cattle suffered a resulting dietary niche compression. Sheep maintained a relatively narrow and constant dietary breadth. Conclusion The increasing dietary niche overlap between livestock species with increasing extent of grassland degradation indicated increased additive effects of cattle and sheep co‐grazing on plant community, and thus stronger effects on plant community composition and diversity.

Abstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

Abstract In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.

Background: Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD.Methods: A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors.Results: After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = −2.58 [-3.29, −1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = −3.47 [-4.97, −1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress.Conclusion: This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.

With the TBM disc cutter box as the subject of investigation, this study addresses the intricate and labor-intensive nature of the assembly process in TBM disc cutter box welding assembly. In order to expedite the assembly of the cutter-head and disc cutter box, an alternative approach utilizing combined bolt connections is implemented in place of welding assembly. Therefore, this article proposes a TBM disc cutter combination bolt connection design method based on AHP. Initially, a hierarchical analysis model is constructed, taking into account the actual conditions of the TBM disc cutter box combined bolt connections. Subsequently, from the array of factors influencing bolted connection performance, five experimental variables were chosen, and an orthogonal experimental layout was devised to examine the stress dispersion in the TBM disc cutter box under conditions of bolted assembly, employing finite element analysis. By conducting extreme difference analysis, the study examined the effects of each experimental factor on the bolt connection performance, and determined the order of importance of each factor more objectively. Thus, the comprehensive weights of each factor were calculated, and the optimal solution of the bolt connection scheme was selected by synthesizing the effects of multiple factors.