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Abstract Spatial heterogeneity and plasticity of the mammalian liver are critical for systemic metabolic homeostasis in response to fluctuating nutritional conditions. Here, a spatially resolved transcriptomic landscape of mouse livers across fed, fasted and refed states using spatial transcriptomics is generated. This approach elucidated dynamic temporal‐spatial gene cascades and how liver zonation—both expression levels and patterns—adapts to shifts in nutritional status. Importantly, the pericentral nuclear receptor Nr1i3 (CAR) as a pivotal regulator of triglyceride metabolism is pinpointed. It is showed that the activation of CAR in the pericentral region is transcriptionally governed by Pparα. During fasting, CAR activation enhances lipolysis by upregulating carboxylesterase 2a, playing a crucial role in maintaining triglyceride homeostasis. These findings lay the foundation for future mechanistic studies of liver metabolic heterogeneity and plasticity in response to nutritional status changes, offering insights into the zonated pathology that emerge during liver disease progression linked to nutritional imbalances.

Abstract The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS‐induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury‐exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury‐aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell‐intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease‐UC interplay, identifying a metabolic target for innovative treatments in liver injury‐complicated colitis.

Abstract Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome‐wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo‐blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin‐dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.

Abstract Aims Apolipoproteins have been reported to be involved in many cardiovascular diseases. The aim of our study was to investigate the prognostic value of apolipoprotein B (ApoB) to apolipoprotein A‐I (ApoA‐I) ratio (ApoB/ApoA‐I) in patients with heart failure (HF). Methods and results We randomly assigned 2400 HF patients into the training cohort (n = 1400) and the validation cohort (n = 1000). Using a receiver operating characteristic curve, we identified the optimal cut‐off value of the ApoB/ApoA‐I in the training cohort as 0.69, which was further validated in the validation cohort. A propensity score matching (PSM) analysis was conducted to eliminate the imbalance in the baseline characteristics of the high and low ApoB/ApoA‐I group. A total of 2242 HF patients were generated in the PSM cohort. We also validated our results with an independent cohort (n = 838). Univariate and multivariate analyses were conducted to explore the independent prognostic value of ApoB/ApoA‐I in the training cohort (n = 1400), the validation cohort (n = 1000), the PSM cohort (n = 2242), and the independent cohort (n = 838). Patients with high ApoB/ApoA‐I ratio had significantly poorer prognosis compared with those with low ApoB/ApoA‐I ratio in the training cohort, the validation cohort, the PSM cohort, and the independent cohort (P

Abstract The aim of this study was to investigate the association between serum albumin to serum creatinine ratio (sACR) and the prognosis of heart failure (HF). In this single‐center prospective cohort study, a total of 2625 patients with HF were enrolled between March 2012 and June 2017. All patients were divided into three groups according to the tertiles of sACR. Of 2625 patients, the mean age was 57.0 ± 14.3 years. During a median follow‐up time of 23 months, 666 end point events occurred. Prognosis analysis indicated that the lowest sACR was significantly associated with higher mortality risk of HF (hazard ratio [HR] = 1.920, 95% confidence interval [CI] = 1.585–2.326, p

Abstract Aims Dilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc‐dependent and calcium‐containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. Methods and results A total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865‐C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P

Abstract Hepatic ischemia–reperfusion (IR) injury remains a common issue lacking effective strategy and validated pharmacological targets. Here, using an unbiased metabolomics screen, this study finds that following murine hepatic IR, liver 3‐hydroxyanthranilic acid (3‐HAA) and quinolinic acid (QA) decline while kynurenine and kynurenic acid (KYNA) increase. Kynurenine aminotransferases 2, functioning at the key branching point of the kynurenine pathway (KP), is markedly upregulated in hepatocytes during ischemia, shifting the kynurenine metabolic route from 3‐HAA and QA to KYNA synthesis. Defects in QA synthesis impair de novo nicotinamide adenine dinucleotide (NAD) biosynthesis, rendering the hepatocytes relying on the salvage pathway for maintenance of NAD and cellular antioxidant defense. Blocking the salvage pathway following IR by the nicotinamide phosphoribosyltransferase inhibitor FK866 exacerbates liver oxidative damage and enhanced IR susceptibility, which can be rescued by the lipid peroxidation inhibitor Liproxstatin‐1. Notably, nicotinamide mononucleotide administration once following IR effectively boosts NAD and attenuated IR‐induced oxidative stress, inflammation, and cell death in the murine model. Collectively, the findings reveal that metabolic rewiring of the KP partitions it away from NAD synthesis in hepatic IR pathophysiology, and provide proof of concept that NAD augmentation is a promising therapeutic measure for IR‐induced liver injury.

Abstract The current study was aimed to explore the beneficial effects of polysaccharides isolated from Laminaria japonica (LP) on gestational diabetes mellitus (GDM) mice. The obtained results demonstrated that the LP improved serum biochemical index, body weight index, and glucose tolerance. Furthermore, the evidence also suggested that the beneficial effects of LP might be attributed to the alternation in gut microbiota by LP supplementation. Particularly, the Turicibacter, a short‐chain fatty acids‐producing bacterium, was found to be up‐regulated. In conclusion, the obtained results indicated that the LP might serve as prebiotic, and might have a great potential to be used as food supplementation for GDM patients.

Abstract Aims Our objective was to investigate the association of common variants in the coding region of advanced glycosylation end‐product specific receptor (RAGE) and the prognosis of heart failure (HF). Methods and results A total of 3394 HF patients were continuously enrolled from January 2009 to August 2018 with a median follow‐up of 20.4 months. Additionally, 2861 healthy subjects also participated in the study. By sequencing these two groups, we identified a common functional missense variant rs2070600 in the coding region of RAGE, which showed a significant association with the prognosis of HF [hazard ratio = 0.53, 95%, confidence interval (CI) = 0.30–0.94, P = 0.03], but no association with the risk of HF (odds ratio = 0.52, 95%, CI = 0.66–1.04, P = 0.106). A series of functional assays revealed that rs2070600‐A, but not ‐G allele, suppressed the expression of RAGE protein by facilitating the binding of miR‐125a‐3p. Furthermore, the RAGE messenger RNA levels of human peripheral blood lymphocytes were reduced in subjects with the rs2070600‐AA genotype compared with subjects with the rs2070600‐GG or ‐AG genotypes. Additionally, our Western blot results from human heart tissue showed increased RAGE expression in HF samples compared with that in healthy donors. Conclusions Our results demonstrate that the common missense variant rs2070600‐A allele is associated with a reduced risk of cardiovascular death and cardiac transplantation by facilitating the binding of miR‐125a‐3p.

Abstract The demand for autonomous motion control of unmanned aerial vehicles in air combat is boosted as taking the initiative in combat appears more and more crucial. Unmanned aerial vehicles inability to manoeuvre autonomously during air combat that features highly dynamic and uncertain manoeuvres of the enemy; however, limits their combat capabilities, which proves to be very challenging. To meet the challenge, this article proposes an autonomous manoeuvre decision model using an expert actor‐based soft actor critic algorithm that reconstructs empirical replay buffer with expert experience. Specifically, the algorithm uses a small amount of expert experience to increase the diversity of the samples, which can largely improve the exploration and utilisation efficiency of deep reinforcement learning. And to simulate the complex battlefield environment, a one‐to‐one air combat model is established and the concept of missile's attack region is introduced. The model enables the one‐to‐one air combat to be simulated under different initial battlefield situations. Simulation results show that the expert actor‐based soft actor critic algorithm can find the most favourable policy for unmanned aerial vehicles to defeat the opponent faster, and converge more quickly, compared with the soft actor critic algorithm.

Abstract Purpose Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. Methods Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia‐inducible factor‐1α (HIF‐1α) by immunohistochemistry. Results Significant differences were observed in tumor size, age, ANM, HER2+, TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF‐1α protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF‐1α are related to the complication of MC in IBC. Of the patients that exhibited high HIF‐1α protein levels, the percentage of high OCN protein levels was larger in patients with ANM. Conclusion Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF‐1α were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF‐1α had a positive correlation in IBC.

Abstract Aiming at addressing the problem of manoeuvring decision‐making in UAV air combat, this study establishes a one‐to‐one air combat model, defines missile attack areas, and uses the non‐deterministic policy Soft‐Actor‐Critic (SAC) algorithm in deep reinforcement learning to construct a decision model to realize the manoeuvring process. At the same time, the complexity of the proposed algorithm is calculated, and the stability of the closed‐loop system of air combat decision‐making controlled by neural network is analysed by the Lyapunov function. This study defines the UAV air combat process as a gaming process and proposes a Parallel Self‐Play training SAC algorithm (PSP‐SAC) to improve the generalisation performance of UAV control decisions. Simulation results have shown that the proposed algorithm can realize sample sharing and policy sharing in multiple combat environments and can significantly improve the generalisation ability of the model compared to independent training.

Abstract Background Intraductal papillary carcinoma (IPC) with invasion is a rare type of breast cancer. There have been few studies on its prognosis, and a nomogram that predicts the prognosis of the disease has not been described to date. Methods Patients who were diagnosed with invasive IPC were screened from the Surveillance, Epidemiology, and End Results (SEER) database. The screened patients were randomly divided into a training cohort and a verification cohort at 7:3. A Cox proportional hazard regression model was performed to analyze the effects of different variables on the risk of death in invasive IPC. A nomogram was constructed to quantify the possibility of death. The concordance index (C‐index), calibration plots, receiver operating characteristic (ROC) curves, and decision curves analysis (DCA) were used to verify the proposed model. Results We included a total of 803 patients diagnosed with invasive IPC, including 563 patients in the training cohort and 240 patients in the validation cohort. The median follow‐up times in the training cohort and validation cohort were 63 months (range, 2–155 months) and 61 months (range, 1–154 months), respectively. For all patients, the probability of death with invasive IPC was 1.4% within 5 years and 5.4% within 10 years. In multivariate analysis, sex, race, tumor size, lymph node status, type of treatment, and chemotherapy were related to the prognosis of invasive IPC. We constructed a nomogram to predict the possibility of death in patients with invasive IPC. Conclusion Patients with invasive IPC had a high survival rate. The proven nomogram was helpful to both patients and clinical decision makers.

Abstract Background Patient satisfaction has been seen as a key criterion when evaluating hospitals and is one of the main focuses of the current health‐care reform in China. This paper aimed to explore patient‐ and hospital‐level factors associated with inpatient satisfaction, which can provide policy implications for the evaluation and development of a patient‐oriented health‐care system. Methods The paper analyses data from the 2017 China National Patient Survey which includes 20 300 inpatients from 131 tertiary hospitals across 31 provinces. Descriptive analysis and multivariable logistic regressions are conducted to identify key factors related to satisfaction. Results Patient sociodemographic characteristics, including gender, age, income and insurance type, are found to be strongly associated with their satisfaction of inpatient experience. In terms of institutional characteristics, hospital type, size, staffing and financial performance are also significantly correlated with inpatient satisfaction. Patients are more satisfied with specialist hospitals and large hospitals measured by the number of beds and surgeries. Hospitals with higher nurse‐to‐bed ratio also receive more satisfaction. The financial performance of hospitals, however, is negatively associated with satisfaction. Conclusion Patient satisfaction contains unique information on service quality and thus should be incorporated into the matrix of hospital evaluation. Meanwhile, differences in patient composition must be adjusted to make fair comparisons across hospitals. Moreover, future reform needs to put greater efforts in the design of comprehensive public insurance scheme, efficient hospital structure and an overall well‐functioning health‐care delivery system in order to better serve patients in China.

In the alkaline geological environment, crystallization blockage of tunnel drainage systems is a common engineering problem and it is difficult to treat. The microscopic mechanism of crystallization and the environmental influence factors are still unclear. Based on the molecular dynamics (MD) technique, this study establishes nanoscale models of CaCO3 and the polyvinyl chloride (PVC) pipe, which is commonly used in drainage systems, under different alkaline environments. The goal is to study the interfacial interaction between CaCO3 and PVC and to reveal the effect of the alkaline environment on the adsorption of CaCO3 by PVC at the atomic scale. Analysis of the adsorption properties predicted by the CaCO3-PVC MD model reveals that CaCO3 molecules attract each other and form many atomic clusters at approximately 0.11 nm from the PVC interface. The peak difference between the strongly alkaline solution and the pure water solution at this distance reaches 31.6%. An in-depth exploration of the differences in adsorption between CaCO3 and PVC under different alkaline environments indicates that the mobility of CaCO3 rises gradually as the alkalinity of the solution increases. In particular, the mobility of CaCO3 in strongly alkaline solutions is approximately 60% higher than that in pure water. Moreover, as the alkalinity of the solution increases, the binding energy of the interface increases, the affinity of the interface increases, and the CaCO3 adsorption capacity gradually increases. The results of laboratory experiments were consistent with the MD simulation results, which indicates that MD simulation can play an important role in the design and evaluation of engineering practice. The innovation of this paper is to try to use the molecular dynamic (MD) technique in the field of materials to explain the practical problems in the field of traditional civil engineering, and the feasibility of molecular dynamic simulation is verified by indoor simulation experiments. The findings of this study can help for a better understanding of crystallization patterns in tunnel drainage pipes in alkaline geological environments and attempt to provide a theoretical basis and new ideas for solving this problem.

Abstract Background Papillary thyroid microcarcinoma (PTMC) is an indolent carcinoma. The cumulative incidence of death from patients with PTMC and the nomogram built based on the competing risks model have not been described. Methods Patients diagnosed with PTMC were selected from the Surveillance, Epidemiology, and End Results (SEER) program (1983‐2015). Cumulative incidence function was utilized to calculate the likelihood of death resulting from thyroid cancer. Gray's test was conducted to examine the difference in the cumulative incidence of death between groups. A proportional subdistribution hazard model was constructed and we further built a nomogram to quantify the likelihood of death using the model. A 10‐fold cross‐validation procedure was adopted to validate the model. Results A total of 46 662 patients diagnosed with PTMC were included. The median follow‐up time was 81 months (range, 1 to 407 months). The 5‐year, 10‐year, and 20‐year probabilities of death from thyroid carcinoma were 0.3%, 0.6%, and 1.4%, respectively. The age at diagnosis, sex, tumor extension, and lymph node involvement were related to the cumulative incidence of death. A proportional subdistribution hazard model was developed. The performance of the model was good. A nomogram was built based on the model to predict the likelihood of death in patients with PTMC. Conclusion The survival rate of patients with PTMC is excellent. The nomogram constructed based on the well‐performed competing risks model is helpful for both patients and clinicians.