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Abstract Aims End‐stage hypertrophic cardiomyopathy (ES‐HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES‐HCM. Methods and results A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF)

A differential game guidance scheme with obstacle avoidance, based on the formulation of a combined linear quadratic and norm-bounded differential game, is designed for a three-player engagement scenario, which includes a pursuer, an interceptor, and an evader. The confrontation between the players is divided into four phases (P1–P4) by introducing the switching time, and proposing different guidance strategies according to the phase where the static obstacle is located: the linear quadratic game method is employed to devise the guidance scheme for the energy optimization when the obstacle is located in the P1 and P3 stages; the norm-bounded differential game guidance strategy is presented to satisfy the acceleration constraint under the circumstance that the obstacle is located in the P2 and P4 phases. Furthermore, the radii of the static obstacle and the interceptor are taken as the design parameters to derive the combined guidance strategy through the dead-zone function, which guarantees that the pursuer avoids the static obstacle, and the interceptor, and attacks the evader. Finally, the nonlinear numerical simulations verify the performance of the game guidance strategy.

Abstract In the era of cloud service popularization, the trustworthiness of service is particularly important. If users cannot prevent the potential trustworthiness problem of the service during long-term use, once the trustworthiness problem occurs, it will cause significant losses. In order to objectively assess the cloud service trustworthiness, and predict its change, this paper establishes a special hierarchical model of cloud service trustworthiness attributes. This paper proposes corresponding management countermeasures around the model, defines the cloud service trustworthiness level, defines the cloud service trusted state based on fuzzy entropy and Markov chain, constructs the membership function of the cloud service trusted state, and realizes the assessment of cloud service trustworthiness and its changes according to the prediction method of Markov chain. Through case analysis and method comparison, it shows that the method proposed in this paper is effective and feasible. This method can provide objective and comprehensive assessment data for the cloud service trustworthiness and its change, makes up the deficiency of fuzzy entropy assessment method. This research has important reference value and significance for the research of cloud service trustworthiness assessment.

Abstract Living cells can rapidly adjust their metabolic activities in response to external stimuli, leading to fluctuations in intracellular temperature and reactive oxygen species (ROS) levels. Monitoring these parameters is essential for understanding cellular metabolism, particularly during dynamic biological processes. In this study, we present a bifunctional nanoprobe capable of simultaneous measurement of ROS levels and temperature within single cells. The nanoprobe features two individually addressable nanoelectrodes, with platinum (Pt) and nickel (Ni) coatings on both sides. At the tip, these two metal layers form a nano-thermocouple, enabling precise intracellular temperature measurements, while the Pt layer facilitates selective ROS detection. This dual functionality allows for real-time monitoring of cellular responses during synergistic chemo-photothermal therapy of cancer cells and zebrafish embryos subjected to mitochondrial toxic stress. Our results demonstrate that the nanoprobe effectively measures increases in temperature and ROS levels in HeLa cells undergoing chemo-photothermal therapy, as well as in chemically stimulated zebrafish embryos. By providing detailed analysis of submicrometer-scale temperature and ROS variations within living cells, this nanoprobe offers valuable insights into cellular processes and holds promise for early disease detection and drug development.

Abstract The low-potential aldehyde oxidation reaction can occur at low potential (~0 VRHE) and release H2 at the anode, enabling hydrogen production with less than one-tenth of the energy consumption required for water splitting. Nevertheless, the activity and stability of Cu catalysts remain inadequate due to the oxidative deactivation of Cu-based materials. Herein, we elucidate the deactivation and reactivation cycle of Cu electrocatalyst and develop a self-reactivating PdCu catalyst that exhibits significantly enhanced stability. Initially, in-situ Raman spectroscopy confirm the cycle involved in electrochemical oxidation and non-electrochemical reduction. Subsequently, in-situ Raman spectroscopy and X-ray absorption fine structure reveal that the Pd component accelerates the rate of the non-electrochemical reduction, thereby enhancing the stability of the Cu-based electrocatalyst. Finally, a bipolar hydrogen production device is assembled utilizing the PdCu electrocatalyst, which can deliver a current of 400 mA cm−2 at 0.42 V and operate continuously for 120 h. This work offers guidance to enhance the stability of the Cu-based electrocatalyst in a bipolar hydrogen production system.

Abstract Optical patterning of colloidal particles is a scalable and cost-effective approach for creating multiscale functional structures. Existing methods often use high-intensity light sources and customized optical setups, making them less feasible for large-scale microfabrication processes. Here, we report an optical patterning method for semiconductor nanoparticles by light-triggered modulation of their surface charge. Rather than using light as the primary energy source, this method utilizes UV-induced cleavage of surface ligands to modify surface charges, thereby facilitating the self-assembly of nanoparticles on a charged substrate via electrostatic interactions. By using citrate-treated ZnO nanoparticles, uniform ZnO patterns with variable thicknesses can be achieved. These multilayered ZnO patterns are fabricated into a UV detector with an on/off ratio exceeding 104. Our results demonstrate a simple yet effective way to pattern semiconductor nanoparticles, facilitating the large-scale integration of functional nanomaterials into emerging flexible and robotic microdevices.

Abstract The electrocatalytic reduction of CO2 to CO is slowed by the energy cost of the hydrogenation step that yields adsorbed *COOH intermediate. Here, we report a hydrogen radical (H•)-transfer mechanism that aids this hydrogenation step, enabled by constructing Ni-partnered hetero-diatomic pairs, and thereby greatly enhancing CO2-to-CO conversion kinetics. The partner metal to the Ni (denoted as M) catalyzes the Volmer step of the water/proton reduction to generate adsorbed *H, turning to H•, which reduces CO2 to carboxyl radicals (•COOH). The Ni partner then subsequently adsorbs the •COOH in an exothermic reaction, negating the usual high energy-penalty for the electrochemical hydrogenation of CO2. Tuning the H adsorption strength of the M site (with Cd, Pt, or Pd) allows for the optimization of H• formation, culminating in a markedly improved CO2 reduction rate toward CO production, offering 97.1% faradaic efficiency (FE) in aqueous electrolyte and up to 100.0% FE in an ionic liquid solution.

Abstract Quantum entanglement acts as a crucial part in quantum computation and quantum information, hence quantifying unknown entanglement is an important task. Due to the fact that the amount of entanglement cannot be achieved directly by measuring any physical observables, it remains an open problem to quantify entanglement experimentally. In this work, we provide an effective way to quantify entanglement for the unknown quantum states via artificial neural networks. By choosing the expectation values of measurements as input features and the values of entanglement measures as labels, we train artificial neural network models to predict the entanglement for new quantum states accurately. Our method does not require the full information about unknown quantum states, which highlights the effectiveness and versatility of machine learning in exploring quantum entanglement.

Abstract Background Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear. Methods We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression. Results An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes. Conclusions E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE. Graphical Abstract

Abstract Recent years have seen increased interest in object detection‐based applications for fire detection in digital images and videos from edge devices. The environment's complexity and variability often lead to interference from factors such as fire and smoke characteristics, background noise, and camera settings like angle, sharpness, and exposure, which hampers the effectiveness of fire detection applications. Limited picture data for fire and smoke scenes further challenges model accuracy and robustness, resulting in high false detection and leakage rates. To address the need for efficient detection and adaptability to various environments, this paper focuses on (1) proposing a cloud‐edge collaborative architecture for real‐time fire and smoke detection, incorporating an iterative transfer learning strategy based on user feedback to enhance adaptability; (2) improving the detection capabilities of the base model YOLOv8 by enhancing the data augmentation method and introducing the coordinate attention mechanism to improve global feature extraction. The improved algorithm shows a 2‐point accuracy increase. After three iterations of transfer learning in the production environment, accuracy improves from 93.3% to 96.4%, and mAP0.5:0.95 increases by nearly 5 points. This program effectively addresses false detection issues in fire and smoke detection systems, demonstrating practical applicability.

Abstract Although septal myectomy is the preferred treatment for medication-refractory hypertrophic obstructive cardiomyopathy (HOCM), the procedure remains subjective. A preoperative planning procedure is proposed using computational fluid dynamics simulations and shape optimization to assist in the objective assessment of the adequacy of the resection. 3 patients with HOCM were chosen for the application of the proposed procedure. The geometries of the preoperative left ventricular outflow tract (LVOT) of patients in the systolic phase were reconstructed from medical images. Computaional fluid dynamics (CFD) simulations were performed to assess hemodynamics within LVOT. Sensitivity analysis was performed to determine the resection extent on the septal wall, and the depth of the resection was optimized to relieve LVOT obstruction while minimizing damage to the septum. The optimized resection was then transferred from systole to diastole to provide surgeons with instructive guidance for septal myectomy. Comparison between preoperative and postoperative hemodynamics showed an evident improvement with respect to the pressure gradient throughout the LVOT. The resected myocardium in the diastolic phase is more extended and thinner than its state in the systolic phase. The proposed preoperative planning procedure may be a viable addition to the current preoperative assessment of patients with HOCM.

Abstract Background This study explores the relationship between serum uric acid(UA) levels and depression. UA is the final product of purine metabolism in the human body, possessing certain physiological functions such as blood pressure regulation, antioxidation, DNA protection, and anti-aging, thereby drawing attention for its potential role in preventing and treating depression. Methods This cross-sectional study includes 32,424 participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, generating a nationally representative database. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Serum uric acid concentration was measured using the uricase-peroxidase coupled method, and participants were divided into quartiles of serum uric acid concentration. Weighted data were calculated according to analysis guidelines. The association between serum uric acid and depressive symptoms was analyzed using weighted multivariable logistic regression models and restricted cubic spline regression analyses. Subgroup analyses were also performed. Results Among 32,424 participants, 3,421 were defined as having depressive symptoms. The crude prevalence of depressive symptoms was 10.5% (weighted prevalence: 9.086% [95% confidence interval: 9.032–9.139%]). Compared with the first quartile, individuals with higher UA levels had a decreased risk of depressive symptoms by 9% (OR: 0.910, 95% CI: 0.797–10.40), 14.6% (OR: 0.854, 95% CI: 0.741–0.983), and 20.5% (OR: 7795, 95% CI: 0.680–0.930), respectively. Further restricted cubic spline regression analysis revealed a nonlinear association between UA and depressive symptoms, with an inflection point of 319.72 µmol/L. Subgroup multivariable weighted logistic regression analysis found that the association between UA and the risk of depressive symptoms remained consistent across all subgroups, demonstrating high stability and reliability. Conclusion This study emphasizes a significant nonlinear negative correlation between serum uric acid and depressive symptoms. This suggests that proper control of serum uric acid levels may play a role in preventing and treating depression.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that currently cannot be completely cured with a great health burden. Since the production of autoantibodies plays a key role in the pathogenesis of SLE, discovering the underlying immunoregulation mechanism of B cells will be helpful for developing promising immunotherapy for SLE. In recent studies, dopamine receptors (DRDs), G protein-coupled receptors that include D1-like and D2-like subtypes, are expressed on B cells and participate in various physiological processes, involving immune responses. However, the regulatory effect of DRDs on B cells has not been determined. Methods This study explored the expression of DRDs on B-cell subsets from SLE patients and healthy individuals. The effects of D1-like receptor on B-cell activation and differentiation were further explored using D1-like receptor agonists or antagonists. RNA-seq and bioinformatics analyses were used to identify specific molecular mechanisms involved. Results The D1-like DRDs on B cells of SLE patients were highly expressed compared with those of healthy controls (HCs). D1-like receptor agonist treatment exacerbated lupus-like symptoms in pristane-induced lupus-like mice, while D1-like receptor antagonists alleviated the lupus-like phenotypes. Inhibition of D1-like receptor signals impeded B-cell differentiation, while activation of D1-like receptor signals could promote B cell differentiation. Further RNA-seq confirmed that PTGS2, a gene related to B-cell differentiation, was up-regulated once the D1-like receptor signals were activated, while BMP6 and IL-24 were up-regulated once the D1-like receptor signals were inhibited. Conclusion D1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.

Highlights Introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue. Highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices in bone tissue engineering. Emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics.

Abstract Salmonella Enteritidis is a major foodborne pathogen throughout the world and the increase in antibiotic resistance of Salmonella poses a significant threat to public safety. Natural nanobodies exhibit high affinity, thermal stability, ease of production, and notably higher diversity, making them widely applicable for the treatment of viral and bacterial infections. Recombinant expression using Lactococcus lactis leverages both acid resistance and mucosal colonization properties of these bacteria, allowing the effective expression of exogenous proteins for therapeutic effects. In this study, nine specific nanobodies against the flagellar protein FliC were identified and expressed. In vitro experiments demonstrated that FliC-Nb-76 effectively inhibited the motility of S. Enteritidis and inhibited its adhesion to and invasion of HIEC-6, RAW264.7, and chicken intestinal epithelial cells. Additionally, a recombinant L. lactis strain secreting the nanobody, L. lactis-Nb76, was obtained. Animal experiments confirmed that it could significantly reduce the mortality rates of chickens infected with S. Enteritidis, together with alleviating the inflammatory response caused by the pathogen. These results provide a novel strategy for the treatment of antibiotic-resistant S. Enteritidis infection in the intestinal tract. Graphical Abstract

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4+ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4+ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology. Despite the increasing global incidence and poor prognosis, the exact pathogenic mechanisms remain elusive. Currently, effective therapeutic targets and treatment methods for this disease are still lacking. This study tried to explore the pathogenic mechanisms of IPF. We found elevated expression of SULF1 in lung tissues of IPF patients compared to normal control lung tissues. SULF1 is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans, playing a critical role in biological regulation. However, the effect of SULF1 in pulmonary fibrosis remains incompletely understood. Our study aimed to investigate the impact and mechanisms of SULF1 in fibrosis. Methods We collected lung specimens from IPF patients for transcriptome sequencing. Validation of SULF1 expression in IPF patients was performed using Western blotting and RT-qPCR on lung tissues. ELISA experiments were employed to detect SULF1 concentrations in IPF patient plasma and TGF-β1 levels in cell culture supernatants. We used lentiviral delivery of SULF1 shRNA to knock down SULF1 in HFL1 cells, evaluating its effects on fibroblast secretion, activation, proliferation, migration, and invasion capabilities. Furthermore, we employed Co-Immunoprecipitation (Co-IP) to investigate the regulatory mechanisms involved. Results Through bioinformatic analysis of IPF transcriptomic sequencing data (HTIPF) and datasets GSE24206, and GSE53845, we identified SULF1 may potentially play a crucial role in IPF. Subsequently, we verified that SULF1 was upregulated in IPF and predominantly increased in fibroblasts. Furthermore, SULF1 expression was induced in HFL1 cells following exposure to TGF-β1. Knockdown of SULF1 suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-β1-driven and non-TGF-β1-driven conditions. We found that SULF1 catalyzes the release of TGF-β1 bound to TGFβRIII, thereby activating the TGF-β1/SMAD pathway to promote fibrosis. Additionally, TGF-β1 induces SULF1 expression through the TGF-β1/SMAD pathway, suggesting a potential positive feedback loop between SULF1 and the TGF-β1/SMAD pathway. Conclusions Our findings reveal that SULF1 promotes fibrosis through the TGF-β1/SMAD pathway in pulmonary fibrosis. Targeting SULF1 may offer a promising therapeutic strategy against IPF.

Abstract Background With the rapid increase of chest computed tomography (CT) images, the workload faced by radiologists has increased dramatically. It is undeniable that the use of artificial intelligence (AI) image‐assisted diagnosis system in clinical treatment is a major trend in medical development. Therefore, in order to explore the value and diagnostic accuracy of the current AI system in clinical application, we aim to compare the detection and differentiation of benign and malignant pulmonary nodules between AI system and physicians, so as to provide a theoretical basis for clinical application. Methods Our study encompassed a cohort of 23 336 patients who underwent chest low‐dose spiral CT screening for lung cancer at the Health Management Center of West China Hospital. We conducted a comparative analysis between AI‐assisted reading and manual interpretation, focusing on the detection and differentiation of benign and malignant pulmonary nodules. Results The AI‐assisted reading exhibited a significantly higher screening positive rate and probability of diagnosing malignant pulmonary nodules compared with manual interpretation (p

Abstract Background Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes. Methods This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group. Results We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p

Abstract In the domain of control engineering, effectively tuning the parameters of proportional-integral-derivative (PID) controllers has persistently posed a challenge. This study proposes a hybrid algorithm (HGJGSO) that combines golden jackal optimization (GJO) and golden sine algorithm (Gold-SA) for tuning PID controllers. To accelerate the convergence of GJO, a nonlinear parameter adaptation strategy is incorporated. The improved GJO is combined with Gold-SA, capitalizing on the expedited convergence speed offered by the improved GJO, coupled with the global optimization and precise search capabilities of Gold-SA. HGJGSO maximizes the strengths of two algorithms, facilitating a comprehensive and balanced exploration and exploitation. The effectiveness of HGJGSO is assessed through tuning the PID controllers for three typical systems. The results indicate that HGJGSO surpasses the comparison tuning methods. To evaluate the applicability of HGJGSO, it is used to tune the cascade PID controllers for trajectory tracking in a quadrotor UAV. The results demonstrate the superiority of HGJGSO in addressing practical challenges.

Abstract Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Abstract Lithium is key for a clean energy transition but faces sustainability challenges in the global supply. Here, we use a bottom-up approach to study the evolution of the global lithium-ion battery industry from 2023 to 2050. The supply and demand trends are predicted to determine the supply potential and allocation structure of primary and secondary lithium. The results indicate a projected global lithium demand of 1.93 million metric tons in 2050, a significant increase of 26.2 times compared to 2023. In the process of global lithium resources shifting from underground reserves to in-use stocks, population and Gross Domestic Product (GDP) influence regions’ lithium endowment and per capita primary consumption, respectively. If the European Union’s new battery regulation is implemented globally, then it is projected to reduce global primary lithium consumption by 1.03 million metric tons by 2050, with a 53.48% decrease in the proportion of primary lithium consumption.

Abstract Background Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. Method This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. Discussion Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. Trial registration ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Abstract The deformation law of pipelines crossing landslide areas is an important prerequisite for the scientific design of pipelines. Most current studies find it difficult to simulate the real stress and strain state of pipelines on site. This study conducted two centrifuge model tests to observe pipeline failure indicators (deformation, stress, strain) and slope failure indicators (crack width, soil pressure, landslide displacement) in response to changes in acceleration. The experimental findings align with the results obtained from numerical simulations. The findings indicate that slope failure with high moisture content is more serious. At a moisture content of 15%, the slope has a maximum displacement of 70 mm in close reach to the buried pipeline. The pipeline has a “bimodal distribution” of strain along its axial length. The largest amount of deformation occurs at a distance of L/4 from the center of the pipeline, and the deformation value is 9000 με. Moreover, the maximum deformation in the mid-span is 21 mm, which corresponds to the result accumulated from the numerical simulation. Thus, the pipeline needs to improve the disaster prevention capabilities at the mid-span and L/4 of the pipeline.

Abstract Photoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.

Abstract Background Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. Methods The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. Results In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: − 0.43, − 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: − 0.61, − 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: − 0.69, − 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. Conclusions This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission. Graphical Abstract

Abstract Background The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. Methods The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. Results In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37–13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38–0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01–0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92–7.59) and 13.63 (95% CI: 9.44–18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73–2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09–0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00–0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32–8.32) and 10.00 (95% CI: 6.09–14.05), respectively. Conclusions The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection. Graphical Abstract

Abstract Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Abstract Background Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Purpose To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. Methods BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1β. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. Results BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/β-catenin signaling, regardless of IL-1β presence or duration of exposure. This inhibition of the Wnt/β-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. Conclusions PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/β-catenin signaling, irrespective of inflammatory conditions.

ObjectivePrevious studies have established a causal relationship between metabolites and breast cancer (BC), but the underlying mechanisms remain unclear. Thus, we aimed to investigate the genetic relationship between metabolites and BC, including its subtypes, using Mendelian randomization (MR) analysis.MethodsUtilizing the latest and most comprehensive summary statistics from genome-wide association studies we conducted an Mendelian randomization study. Data on 233 metabolites, used as exposure variables, were obtained from a study involving 136,016 participants. BC data, used as outcome variables, were sourced from a study comprising 122,977 cases and 105,974 controls. We used the inverse-variance weighted method as the primary approach, along with three supplementary methods, to assess the causal relationship. We also used Cochran’s Q test to detect heterogeneity and MR-Egger regression to examine the presence of horizontal pleiotropy.ResultsUpon analyzing 233 metabolites across 11 classes in relation to BC, we found six classes of metabolites (fatty acids glycerides and phospholipids, lipoprotein subclasses, lipids, apolipoproteins, and lipoprotein particle size) associated with overall BC. Five classes of metabolites (fatty acids glycerides and phospholipids, lipoprotein subclasses, lipids, and lipoprotein particle size) were related to estrogen receptor (ER) + BC, and eight classes of metabolites (fatty acids, amino acids, glycerides and phospholipids, lipoprotein subclasses, lipids, apolipoproteins, glycolysis-related metabolites, and lipoprotein particle size) were linked to ER- BC.ConclusionOur study demonstrates a genetic causal relationship between most metabolites and BC, confirming the link between these factors. This research provides a significant foundation for the prevention and treatment of BC.

Abstract Two indices, indicating the regional average stiffness and the pace of strain hardening respectively, are derived from the nonlinear stress–strain behavior obtained from biomechanical analysis of aneurysm. A comprehensive method based on electrocardiographic‐gated multidimensional dynamic computed tomography angiography (MD CTA) is developed for extracting these mechanical characteristics in vivo. The proposed indices are evaluated by 26 cases including 9 healthy, one aortosclerosis, and 16 abdominal aortic aneurysm cases. The difference of SSI and dSSI value between aneurysmal and healthy groups is up to orders in magnitude. Significant correlation of these indices with the clinical indicator of aneurysm diameter is found. Logistic models based on these indices are capable to sharply discriminate the healthy and the aneurysmal arteries with AUC>0.98. This work introduces new tools and new indices for aortic mechanical assessment which may shed light on understanding the mechanical condition, pathological state and eventually benefit clinical decision‐making.

Background: PFAS pose a significant threat to cardiovascular health and increase the risk of atherosclerotic cardiovascular disease (ASCVD). However, there is limited research evidence regarding the mechanisms by which PFAS affect the risk of ASCVD and the exposure-risk (E-R) relationship. The effect of kidney function in the relationship between PFAS and ASCVD risk has not been adequately validated. Objective: This study aims to explore the mechanisms by which four PFAS (Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), Perfluorohexanesulfonic acid (PFHS), and Perfluorononanoic acid (PFNA)) affect the risk of ASCVD and to verify and discuss the mediating effect of kidney function in this impact. Methods: This study utilizes data from 14,607 participants in the NHANES 2005–2018 to conduct a cross-sectional study. Initially, Generalized Linear Model (GLM) and Restricted Cubic Splines models are used to assess the impact of four PFAS on ASCVD risk and the E-R relationship. Subsequently, the Weighted Quantile Sum regression (WQS) model is used to evaluate the relationship between mixed four PFAS exposure and ASCVD risk. Finally, Directed Acyclic Graphs (DAG) and causal mediation models are used to confirm and analyze whether the decline in kidney function mediates the impact of four PFAS on ASCVD risk. Results: The results from GLM and WQS models indicate that both singular and mixed four PFAS exposures are associated with an increased risk of ASCVD. The E-R curves between four PFAS singular and mixed exposures and ASCVD risk are all characterized by nonlinearity. The results from DAG and causal mediation models clearly indicate that the decline in kidney function plays a significant mediating role in the relationship between four PFAS and ASCVD risk. Conclusion: Exposure levels of four PFAS do not significantly increase the risk of ASCVD unless they reach a certain threshold, and the decline in kidney function exerts a significant mediating effect in the relationship between four PFAS exposure and ASCVD risk.

BackgroundSystemic inflammation (SI) and insulin resistance (IR) are correlated to the progression of gastrointestinal (GI) cancer. Therefore, this study aimed to analyze the potential clinical value of the C-reactive protein-triglyceride-glucose index (CTI) in relation to SI and IR in patients with GI cancer.MethodsThis prospective cohort study included patients with GI cancer. Patient data were collected from Fujian Cancer Hospital as an external validation cohort. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses were used to predict the efficacy and accuracy of CTI survival prediction. Multivariate survival analysis was performed to evaluate the potential prognostic value of the CTI. Multiple logistic regression was performed to evaluate the relationship between the CTI and 90-day and 180-day mortalities.ResultsWe divided 1520 patients with GI cancer (mean age, 60.39 ± 11.3 years; male sex, 67%) into a training cohort and internal validation cohort; the external validation cohort included 476 patients. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses of all cohorts indicated that the CTI could reliably and accurately predict the short- and long-term survival outcomes of patients with GI cancer. Multivariate survival analysis showed that for each standard deviation increase in the CTI, the risk of death increased by 32%, 21%, and 40% in the training, internal validation, and external validation cohorts, respectively. A high CTI was correlated to worse survival in patients with GI cancer (training cohort, hazard ratio [HR]=1.67, 95% confidence interval [CI]=1.35–2.08; internal validation cohort, HR=1.51, 95% CI=1.07–2.14, and external validation cohort, HR=1.59, 95% CI=1.18–2.13). In different tumor subgroups, a high CTI predicted worse survival outcomes for upper GI cancer (HR=1.54, 95% CI=1.18–2.01) and lower GI cancer (HR=1.98, 95% CI=1.36–2.86). Multivariate logistic regression analysis showed that a high CTI was positively correlated with 90-day (odds ratio [OR]=3.25, 95% CI=1.75–6.23) and 180-day mortalities (OR=2.66, 95% CI=1.72–4.15).ConclusionsThe CTI is related to SI and IR and can predict the short- and long-term prognosis of patients with GI cancer. Evaluation of the CTI could provide clinicians with an effective tool for predicting the prognosis of patients with GI cancer.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=31813, identifier ChiCTR1800020329.

Time-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities. However, the effect of TRE on the human immune system, especially on immunosenescence, intestinal microbiome, and metabolism remains unclear. We conducted a 30-day 16:8 TRE single-arm clinical trial with 49 participants. Participants consumed daily meals from 9 a.m. to 5 p.m., provided by a nutrition canteen with a balanced, calorie-appropriate nutrition, which is designed by clinical nutritionists (ChiCTR2200058137). We monitored weight changes and weight-related parameters and focused on changes in the frequency of CD4+ senescent T cells, immune repertoire from peripheral blood, as well as serum metabolites and gut microbiota. We found that up to 95.9 % of subjects experienced sustained weight loss after TRE. The frequency of circulating senescent CD4+ T cells was decreased, while the frequency of Th1, Treg, Tfh-like, and B cells was increased. Regarding the immune repertoire, the proportions of T cell receptor alpha and beta chains were increased, whereas B cell receptor kappa and lambda chains were reduced. In addition, a reduced class switch recombination from immunoglobulin M (IgM) to immunoglobulin A (IgA) was observed. TRE upregulated the levels of anti-inflammatory and anti-aging serum metabolites named sphingosine-1-phosphate and prostaglandin-1. Additionally, several anti-inflammatory bacteria and probiotics were increased, such as Akkermansia and Rikenellaceae, and the composition of the gut microbiota tended to be “younger”. Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay “young”. Clinical Trial Registration URL: https://www.chictr.org.cn/showproj.html?proj=159876.

Ultra High Performance Concrete (UHPC) is a new concrete material with excellent performance. Many practices have shown that UHPC tends to have excessive compressive properties but insufficient tensile properties. The electromagnetic alignment technology of steel fibers enhances the efficiency of steel fiber utilization. It greatly enhances the flexural strength, but the ductility of the flexural specimens is poor. Furthermore, it is required to use environmentally friendly fibers to partially replace steel fibers, as the incorporation of steel fibers adds to carbon emissions. This research explores the tensile behaviors of hybrid steel-macro basalt fiber UHPC to search for low-carbon construction materials with great mechanical behaviors. The effects of two key parameters, the alignment of steel fibers and the mixing ratio of steel-macro basalt fibers, on the tensile properties were systematically analyzed. Aligned steel fiber was classified as parallel to the tensile direction, vertical to the tensile direction, and undirected. In the steel-macro basalt fiber blend, the total volume doping of 1.5 % was kept unchanged, and a total of four groups of blend schemes were established. Uniaxial tensile tests were performed, and the elastic modulus, tensile strength, and tensile ductility coefficient of the specimens were calculated to produce the stress-strain relationship curves. The results reveal that the parallel orientation of steel fibers could significantly enhance the tensile strength, and the ductility of the material is increased considerably by blending macro basalt fibers. Carbon emissions can be effectively reduced while maintaining superior tensile properties through an optimized combination of steel fiber orientation and steel-macro basalt fiber blend ratio. Finally, the tensile strength prediction equations for this material are proposed by considering the impact of the two fibers on the tensile properties separately.

Abstract Background: Cognitive impairment is the most common long‐term complication in children with congenital heart disease (CHD) and is closely related to the brain network. However, little is known about the impact of CHD on brain network organization. This study aims to investigate brain structural network properties that may underpin cognitive deficits observed in children with Tetralogy of Fallot (TOF). Methods: In this prospective study, 29 preschool‐aged children diagnosed with TOF and 19 without CHD (non‐CHD) were enrolled. Participants underwent diffusion tensor imaging (DTI) scans alongside cognitive assessment using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence—fourth edition (WPPSI‐IV). We constructed a brain structural network based on DTI and applied graph analysis methodology to investigate alterations in diverse network topological properties in TOF compared with non‐CHD. Additionally, we explored the correlation between brain network topology and cognitive performance in TOF. Results: Although both TOF and non‐CHD exhibited small‐world characteristics in their brain networks, children with TOF significantly demonstrated increased characteristic path length and decreased clustering coefficient, global efficiency, and local efficiency compared with non‐CHD (p < 0.05). Regionally, reduced nodal betweenness and degree were found in the left cingulate gyrus, and nodal efficiency was decreased in the right precentral gyrus and cingulate gyrus, left inferior frontal gyrus (triangular part), and insula (p < 0.05). Furthermore, a positive correlation was identified between local efficiency and cognitive performance (p < 0.05). Conclusion: This study elucidates a disrupted brain structural network characterized by impaired integration and segregation in preschool TOF, correlating with cognitive performance. These findings indicated that the brain structural network may be a promising imaging biomarker and potential target for neurobehavioral interventions aimed at improving brain development and preventing lasting impairments across the lifetime.

Abstract Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota‐derived lipopolysaccharides (LPS), accumulating to the liver through the gut‐liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS‐induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan‐horse strategy is proposed using an oral dextran‐carbenoxolone (DEX‐CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut‐liver axis for simultaneous modulation of hepatic inflammation and gut microbiota. In the orthotopic HCC model, a 95–45% reduction in the relative abundances of LPS‐associated microbiota is observed, especially Helicobacter, caused by DEX‐CBX treatment over phosphate‐buffered saline (PBS) treatment. Notably, a dramatic increase (37‐fold over PBS) in the abundance of Akkermansia, which is known to strengthen systemic immune response, is detected. Furthermore, DEX‐CBX significantly increased natural killer T cells (5.7‐fold) and CD8+ T cells (3.9‐fold) as well as decreased M2 macrophages (59% reduction) over PBS treatment, resulting in a tumor suppression rate of 85.4%. DEX‐CBX is anticipated to offer a novel strategy to precisely modulate hepatic inflammation and the gut microbiota to address both the symptoms and root causes of LPS‐induced immunosuppression in HCC.

Aim of the StudyTo study the changes in the chemical composition and medicinal effects of black ginseng during processing.Materials and MethodsThe contents of ginsenosides Rg1, Re, Rh1, Rb1, 20-(S)-Rg3, 20-(R)-Rg3, and Rg5 were determined using high-performance liquid chromatography (HPLC), and the percentage of rare saponins was calculated. Furthermore, changes in the contents of reducing sugars and amino acids (i.e., Maillard reaction (MR) substrates) were measured to assess the relationship between processing and the MR. Compounds were identified using HPLC-MS and their cleavage patterns were analyzed. Gene co-expression network bioinformatics techniques were applied to identify the pharmacological mechanism of black ginseng.ResultsThe changes in the physicochemical characteristics of black ginseng during processing were determined based on the MR. Rare saponins accumulated during black ginseng processing. In addition, reducing sugars were produced through polysaccharide pyrolysis and the MR; thus, their content initially increased and then decreased. The amino acid content gradually decreased as the number of evaporation steps increased, indicating that both amino acids and reducing sugars acted as substrates for the MR during black ginseng processing. Thirty-one saponins, 18 sugars, and 58 amino acids were identified based on the MS analysis. Transcriptomics results demonstrated that black ginseng can regulate signaling pathways such as the TNF, IL-17, MAPK, and PI3K-Akt pathways. This finding helps us understand the observed proliferation and differentiation of immune-related cells and positively regulated cell adhesion.

The livestock industry has long been a hotspot environment for antibiotic resistance genes, with smallholder farming still holding a significant position in pig farming. However, the microbial antibiotic resistance and pathogen risks in pigs under the smallholder farming model remain unclear. We systematically analyzed the antibiotic resistance and microbial composition of pig feces from smallholder and large-scale farming models in Sichuan. The results indicated a lower abundance of antibiotic resistance genes (ARGs) and similar microbial composition in smallholder farming compared to large-scale farming. Beneficial bacteria were more abundant in small-scale farming, whereas large-scale farming exhibited more ARGs, virulence genes, and human pathogenic bacteria (HPBs), including ESBL Escherichia coli strains closely related to human strains, indicating higher zoonotic risk. The findings suggest that smallholder farming presents a relatively better microbial composition and resistance profile, highlighting its advantages over large-scale farming in terms of pig and human health. It is noteworthy that a considerable proportion of HPBs carrying ARGs still exist in the feces from smallholder farming, and given the openness of fecal handling, there remains a high risk of transmitting ARGs and pathogens to humans.

Reducing fertilizer-N rate, applying a nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. A field 15N tracer study was conducted to compare their effectiveness on fertilizer-N fates during the maize growing season in Northeast China. The following six treatments were used: (1) no N fertilization (control); (2) 200 kg urea-N ha−1 (100%N); (3) 200 kg urea-N ha−1 and straw (100%N + S); (4) 160 kg urea-N ha−1 (80%N); (5) 160 kg urea-N ha−1 and NI (Nitrapyrin in this study) (80%N + NI); and (6) 160 kg urea-N ha−1, NI, and straw (80%N + NI + S). The results showed that the five N fertilization treatments yielded 16–25% more grain and 39–60% more crop N uptake than the control, but the differences among the five treatments were not statistically significant. Compared with the 100%N, 20% fertilizer-N reduction (80%N) decreased the 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (NUE15N, 60% vs. 50%). Compared with the 80%N, NI co-application (80%N + NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly. Straw incorporation decreased fertilizer-N retention in soil compared with NI co-application because it promoted NUE15N significantly. In conclusion, the results demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract Background Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. Methods This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. Discussion The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. Trial registration China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Abstract Background Off-pump coronary artery bypass grafting (OPCABG) presents distinct hemodynamic characteristics, yet the relationship between intraoperative hypotension and short-term adverse outcomes remains clear. Our study aims to investigate association between intraoperative hypotension and postoperative acute kidney injury (AKI), mortality and length of stay in OPCABG patients. Methods Retrospective data of 494 patients underwent OPCABG from January 2016 to July 2023 were collected. We analyzed the relationship between intraoperative various hypotension absolute values (MAP > 75, 65 65 mmHg emerges as a significant independent protective factor for AKI in OPCABG and IOH is related to length of hospital stay. Proactive intervention targeting intraoperative hypotension may provide a potential opportunity to reduce postoperative renal injury and hospital stay. Trial registration ChiCTR2400082518. Registered 31 March 2024. https://www.chictr.org.cn/bin/project/edit?pid=225349 .

Abstract Objectives Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low‐dose computed tomography (LDCT) screening for the high‐risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real‐world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick‐slice LDCT scanning. Methods A total of 29 296 subjects who underwent low‐dose thick‐slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low‐dose thin‐slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. Results The positive rate of LDCT screening in the thin‐slice scanning group was significantly higher than that in the thick‐slice scanning group (20.1% vs. 14.4%, p

With the rise of computing power networks, a novel infrastructure centered around computational power has emerged as a key driver in the development of the information economy. Data, recognized as a crucial production factor in the digital era, serves as a vital pillar for constructing new development paradigms. The data factor market, acting as the link between data and computational power networks, is particularly critical. Its robust operation directly affects the sustainable development of computational power networks and is provided with crucial support for the information economy system. Therefore, the data products were treated as the focal point, while the processes involved in the data factor market and the inherent connections among these components were introduced. Subsequently, the existing work on three key aspects of the data factor market was studied, including data value, data pricing, and data transactions. Regarding data value assessment, key aspects such as relative data value evaluation were discussed, introducing indicator systems, indicator weights, and value indices. For data asset value assessment, traditional methods such as the cost method, income method, and market method were discussed, as well as emerging methods based on machine learning. In terms of data pricing models, existing methods were categorized into two main types: pricing for dataset products and pricing for data service products. Seven pricing methods were summarized, and the advantages, disadvantages, and applicable scenarios of each method were further analyzed. Regarding data transaction systems, the applications of centralized and distributed architectures in the data trading market were analyzed from the perspective of system architecture. The current status and prospects of both on-exchange and over-the-counter trading modes were then introduced.

Abstract Background and aims The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. Method The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan–Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25–1.45, P

Purpose – Adopting adaptive behavior has become a basic measure for farmers because the increasingly severe climate change is affecting agricultural production. Perception is a critical first step in adopting adaptive behaviors. Livelihood resilience represents a farmer's ability to adapt to climate change. Therefore, this article aims to explore the impact of livelihood resilience and climate change perception on the climate change adaptation behavior of farmers in the Qinling Mountains region of China. Design/methodology/approach – In this study, 443 micro-survey data of farmers are obtained through one-on-one interviews with farmers. The Logit model and Poisson regression model are used to empirically examine the impact of farmers' livelihood resilience and climate change perception on their climate change adaptation behaviors. Findings – It was found that 86.68% of farmers adopt adaptive behaviors to reduce the risks of facing climate change. Farmers' perception of extreme weather has a significant positive impact on their adaptive behavior under climate change. The resilience of farmers' livelihoods and their perception of rainfall have a significant positive impact on the intensity of their adaptive behavior under climate change. Climate change adaptation behaviors are also different for farmers with different levels of livelihood resilience. Originality/value – Based on the results, policy recommendations are proposed to improve farmers' perception of climate change, enhance the sustainability of farmers' adaptive behavior to climate change, strengthen emergency management and infrastructure construction and adjust and upgrade farmers' livelihood models.

This study focuses on the pretreatment and characterization of natural fibers from the bamboo shoot shell (BSS) of Phyllostachys heterocycla to determine their suitability as biorefining materials. The discarded bamboo shoot shell was used as a source of fibers, which were analyzed for their physical, chemical, and microstructure properties. Fourier transform infrared spectroscopy, X-ray diffraction spectra, and scanning electron microscopy confirmed that a mixture of sodium hydroxide immersion plus high-pressure steam treatment allowed the cellulose structure to be disrupted, providing more adsorption sites for cellulases. Gas chromatography mass spectrometry (GC-MS) also showed that the pretreatment exposed the internal structure of the fibers and that high-mass silicon compounds were present in the eluted solution. After adding the cellulase produced by Trichoderma viride and Aspergillus niger, the reducing sugar yield was increased by 268% and 251%, compared to unpretreated BSS fibers. This strategy may apply to many industries, especially biorefining and lignocellulose biotransformation technology.