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Abstract EphrinB2 (erythropoietin-producing hepatoma interactor B2) is a key Eph/ephrin family member, promoting angiogenesis, vasculogenesis, and lymphangiogenesis during embryonic development. However, the role of EphrinB2 in cardiac lymphangiogenesis following myocardial infarction (MI) and the potential molecular mechanism remains to be demonstrated. This study revealed that EphrinB2 prevented ischemic heart post-MI from remodeling and dysfunction by activating the cardiac lymphangiogenesis signaling pathway. Deletion of EphrinB2 impaired cardiac lymphangiogenesis and aggravated adverse cardiac remodeling and ventricular dysfunction post-MI. At the same time, overexpression of EphrinB2 stimulated cardiac lymphangiogenesis which facilitated cardiac infiltrating macrophage drainage and reduced inflammation in the ischemic heart. The beneficial effects of EphrinB2 on improving clearance of inflammatory response and cardiac function were abolished in Lyve1 knockout mice. Mechanistically, EphrinB2 accelerated cell cycling and lymphatic endothelial cell proliferation and migration by activating CDK5 and CDK5-dependent ISL1 nuclear translocation. EphrinB2 enhanced the transcriptional activity of ISL1 at the VEGFR3 (FLT4) promoter, and VEGFR3 inhibitor MAZ51 significantly diminished the EphrinB2-mediated lymphangiogenesis and deteriorated the ischemic cardiac function. We uncovered a novel mechanism of EphrinB2-driven cardiac lymphangiogenesis in improving myocardial remodeling and function after MI.

Abstract Objective Rheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients. Methods This single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group. Results Out of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab. Conclusion Inadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.

Abstract The concept of the Human Digital Twin (HDT) has recently emerged as a new research area within the domain of digital twin technology. HDT refers to the replica of a physical-world human in the digital world. Currently, research on HDT is still in its early stages, with a lack of comprehensive and in-depth analysis from the perspectives of universal frameworks, core technologies, and applications. Therefore, this paper conducts an extensive literature review on HDT research, analyzing the underlying technologies and establishing typical frameworks in which the core HDT functions or components are organized. Based on the findings from the aforementioned work, the paper proposes a generic architecture for the HDT system and describes the core function blocks and corresponding technologies. Subsequently, the paper presents the state of the art of HDT technologies and their applications in the healthcare, industry, and daily life domains. Finally, the paper discusses various issues related to the development of HDT and points out the trends and challenges of future HDT research and development.

Abstract Background Abnormal heart rate recovery (HRR), representing cardiac autonomic dysfunction, is an important predictor of cardiovascular disease. Prolonged sedentary time (ST) is associated with a slower HRR. However, it is not clear how much moderate-to-vigorous physical activity (MVPA) is required to mitigate the adverse effects of sedentary behavior on HRR in young and middle-aged adults. This study aimed to examine the joint association of ST and MVPA with abnormal HRR in this population. Methods A cross-sectional analysis was conducted on 1253 participants (aged 20–50 years, 67.8% male) from an observational study assessing cardiopulmonary fitness in Fujian Province, China. HRR measured via cardiopulmonary exercise tests on a treadmill was calculated as the difference between heart rate at peak exercise and 2 min after exercise. When the HRR was ≤ 42 beats·minute−1 within this time, it was considered abnormal. ST and MVPA were assessed by the IPAQ-LF. Individuals were classified as having a low sedentary time (LST [

Abstract. As a complementary and alternative medicine (CAM), traditional Chinese medicine (TCM) represents an established medical system with a rich history and abundant clinical experience. TCM is an empirical medicine, the process of which is analogous to ChatGPT’s learning and development model. In TCM, inquiry is a relatively objective way of traditional syndrome differentiation. Although various artificial intelligence systems related to TCM consultation exist, their interactive abilities remain limited. The study standardized the primary complaint and instructed ChatGPT to simulate a TCM practitioner, conducting three comprehensive inquiry tests. The results yielded unexpected conclusions, revealing that ChatGPT could simulate a TCM practitioner’s inquiry with patients, confirming its potential in the field of TCM inquiry. However, current applications still pose certain limitations and risks. Hence, to integrate ChatGPT-like language models with traditional TCM AI to establish an associative mode that can facilitate TCM diagnosis and treatment with more convenience and standardization is crucial, yet at the same time, it should be treated very carefully.

There is a pronounced coupling vibration between the catenary and pantograph during operation for high-speed railways. In this paper, a pantograph–catenary coupling vibration model is constructed to investigate the vibration characteristics under various working conditions. Two different types of catenaries (simple and elastic chain types) are simulated and compared using the finite element method. The pantograph is simplified into a mass–spring–damping combination member, the contact and messenger wires are set to linear beam cells, and the dropper and stitch wire are set to truss cells. The results suggest that the vibration characteristics of the two types of catenaries and pantograph exhibit different trends. The maximum stresses of the messenger wire, dropper, and contact wire do not follow a monotonically increasing trend with the train speed. The maximum stress of the messenger wire under the simple chain type of catenary is higher when the initial contact force increases from 80 to 120 N. However, the maximum stress under the elastic chain type of catenary is higher when the initial contact force is 60 or 140 N. Except for the initial contact force of 140 N, the maximum stresses of the dropper and contact wire under the simple chain type of catenary are lower than those under the elastic chain type. This work provides a valuable reference for optimizing the design of pantograph–catenary systems.

In deterministic mobile edge computing (MEC) networks, accurately predicting latency is critical for optimizing resource allocation and enhancing quality of service (QoS). This paper introduces a novel approach leveraging attention mechanism enhanced long short-term memory (LSTM) networks to predict latency in MEC networks. The proposed model integrates attention mechanisms into LSTM networks to capture temporal dependency and emphasize relevant features in the input data, thereby improving the prediction accuracy. T extensive experiments are conducted by using practical MEC network data, demonstrating that the proposed approach significantly outperforms traditional LSTM and other baseline models in terms of prediction accuracy and computational efficiency. Additionally, we analyze the impact of various configurations in the attention mechanism and LSTM on the model performance, providing insights into the optimal settings. The findings of this study contribute to the advancement of latency prediction techniques in deterministic MEC networks, facilitating more efficient and reliable network management.

This study systematically examines the energy dissipation mechanisms and ballistic characteristics of foam sandwich panels (FSP) under high-velocity impact using the explicit non-linear finite element method. Based on the geometric topology of the FSP system, three FSP configurations with the same areal density are derived, namely multi-layer, gradient core and asymmetric face sheet, and three key structural parameters are identified: core thickness (tc), face sheet thickness (tf) and overlap face/core number (no). The ballistic performance of the FSP system is comprehensively evaluated in terms of the ballistic limit velocity (BLV), deformation modes, energy dissipation mechanism, and specific penetration energy (SPE). The results show that the FSP system exhibits a significant configuration dependence, whose ballistic performance ranking is: asymmetric face sheet > gradient core > multi-layer. The mass distribution of the top and bottom face sheets plays a critical role in the ballistic resistance of the FSP system. Both BLV and SPE increase with tf, while the raising tc or no leads to an increase in BLV but a decrease in SPE. Further, a face-core synchronous enhancement mechanism is discovered by the energy dissipation analysis, based on which the ballistic optimization procedure is also conducted and a design chart is established. This study shed light on the anti-penetration mechanism of the FSP system and might provide a theoretical basis for its engineering application.

Abstract Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKβ/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKβ in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKβ. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKβ protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKβ. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKβ. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKβ in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKβ to safeguard renal tubular function in the management of DKD.

Abstract Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

The surface coating technology, encompassing ceramics, refractory materials, metallic alloys containing Al or Si, and multicomponent composites, presents a viable approach to improve the corrosion resistance of ferritic/martensitic (F/M) steels with (9–12) wt.% Cr in liquid lead-bismuth eutectic (LBE) environment. Among these coating materials, chromium (Cr) coating emerges as a particularly noteworthy option. This study specifically focused on depositing a 3 μm thick Cr coating on on T91 and SIMP steels using magnetron sputtering. Subsequently, the corrosion behavior of the Cr coating was investigated in LBE at temperatures of 600 °C and 700 °C. The results revealed that, after 300 h at 600 °C, T91 and SIMP steels formed oxide scales with approximately 32.6 μm and 19.3 μm thicknesses, respectively. At 700 °C for 140 h, these oxide scales increased to about 82.4 μm and 73.1 μm for T91 and SIMP steels, respectively. However, the application of a Cr coating resulted in the formation of a dense layer of chromium oxide with a thickness of 4–5 μm. This layer effectively impeded oxygen diffusion and Fe migration leading to a significant reduction in the corrosion rate of the steel. Notably, the Cr coating maintained secure attachment to the steel even after exposure to high-temperature LBE corrosion. These findings underscore the capacity of coating to markedly enhance the corrosion resistance of T91 and SIMP steels in high-temperature LBE environments, providing robust protection against the detrimental effects of challenging conditions. Consequently, Cr coating emerges as a promising solution for future fission nuclear reactors.

Ultra-intense laser-plasma wakefield accelerator possess several superior properties compared with the traditional radio-frequency accelerators. These characteristics include femtosecond duration, micro-source size, and ultra-dense beam density, result in highly advantageous for various important applications. In this paper, we reviewed the generation of ultra-intense and high charge electron beam based on laser-plasma acceleration and its nuclear applications in Shanghai Jiao Tong University, including the production of 10 s nC charge beams, the generation of ultra-high flux neutron source on the order of 1019 n/cm2/s, and the excitation of nuclear isomers with the peak efficiency on the order of 1015 particle/s. This laser driving ultra-dense electron source, in conjunction with the plasma environment, presents immense potential in addressing critical problems in astrophysics, and facilitating various nuclear applications. Based on above progress in nuclear astrophysics, a new research plateform about laboratory astrophysics with a 2.5 PW laser will be constructed in TDLI institute.

Background: Little is known about the combined effect of bisphenol mixtures and metal mixtures on type 2 diabetes mellitus (T2DM) risk, and the mediating roles of metabolites. Methods: The study included 606 pairs of T2DM cases and controls matched by age and sex, and information of participants was collected through questionnaires and laboratory tests. Serum bisphenol and plasma metal concentrations were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Widely targeted metabolomics was employed to obtain the serum metabolomic profiles. Conditional logistic regression models were used to assess the single associations of bisphenols and metals with T2DM risk after multivariable adjustment. Additionally, the joint effects of bisphenol mixtures and metal mixtures were examined using quantile-based g-computation (QG-C) models. Furthermore, differential metabolites associated with T2DM were identified, and mediation analyses were performed to explore the role of metabolites in the associations of bisphenols and metals with T2DM risk. Results: The results showed bisphenol mixtures were associated with an increased T2DM risk, with bisphenol A (BPA) identified as the primary contributor. While the association between metal mixtures and T2DM remained inconclusive, cobalt (Co), iron (Fe), and zinc (Zn) showed the highest weight indices for T2DM risk. A total of 154 differential metabolites were screened between the T2DM cases and controls. Mediation analyses indicated that 9 metabolites mediated the association between BPA and T2DM, while L-valine mediated the association between Zn and T2DM risk. Conclusions: The study indicated that BPA, Co, Fe, and Zn were the primary contributors to increased T2DM risk, and metabolites played a mediating role in the associations of BPA and Zn with the risk of T2DM. Our findings contribute to a better understanding of the mechanisms underlying the associations of bisphenols and metals with T2DM.

ObjectiveThis study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications.MethodsPatients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators.ResultsThirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-β exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15).ConclusionThe Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.

Al-containing MAX phase ceramic has demonstrated great potential in the field of high-performance low-voltage electrical contact material. Elucidating the anti-arc erosion mechanism of the MAX phase is crucial for further improving performance, but it is not well-understood. In this study, Ag/Ti3AlC2 electrical contact material was synthesized by powder metallurgy and examined by nanoindentation techniques such as constant loading rate indentation, creep testing, and continuous stiffness measurements. Our results indicated a gradual degradation in the nano-mechanical properties of the Ti3AlC2 reinforcing phase with increasing arc erosion times, although the rate of this degradation appeared to decelerate over arc erosion times. Specifically, continuous stiffness measurements highlighted the uneven mechanical properties within Ti3AlC2, attributing this heterogeneity to the phase’s decomposition. During the early (1–100 times) and intermediate (100–1000 times) stages of arc erosion, the decline in the nano-mechanical properties of Ti3AlC2 was primarily ascribed to the decomposition of Ti3AlC2 and limited surface oxidation. During the later stage of arc erosion (1000–6200 times), the inner region of Ti3AlC2 also sustained arc damage, but a thick oxide layer formed on its surface, enhancing the mechanical properties and overall arc erosion resistance of the Ag/Ti3AlC2.

The most essential cause of the fracture of the dropper is the effect of alternating stress for a long time. Therefore, in order to ensure the safe operation of high-speed railways, the influence of moving loads on the stress of a dropper was investigated in this study. Due to a high-voltage catenary system, it is very difficult to measure the moving load. Thus, the uplift displacement measured by some software and hardware devices has been applied to the contact wire instead of the moving load. The response equation for the contact wire has been derived so as to determine the initial and boundary conditions of each dropper. Then it was combined with the equation for vibration analysis of the dropper and the stress of each dropper was calculated by using the finite-difference method based on a written MATLAB program. The results show that the dropper stress, during a certain period goes through two stages of immediate rebound and bending compression when the uplift displacement is large. After the pantograph passes, the vibration of the dropper tends to be smooth; also, dropper stress variation with timecan be described by three stages: immediate rebound, vibration attenuation, and bending compression. In addition, the maximum tensile stress of dropper Ⅳ was the highest. It indicates that dropper Ⅳ was more prone to fracture than other droppers.

The off-line discharge between the pantograph and catenary (PAC) occurs frequently in the actual operation of an electric locomotive, which affects the quality of the received current and the service life of the pantograph. The current experiments on the off-line discharge between the PAC are mainly low-power ones and the models established are static. To study the electrical behaviors during the PAC relative motion under the actual working conditions, in this paper, the voltage and current of the contact wire (CW) during its motion are measured. And the electrical behaviors during the rise, fall and reciprocating motions of the pantograph are investigated by combining a finite element method (FEM) model based on the magnetohydrodynamics with the auto transformer (AT) traction network circuit and moving mesh method. It is found that the harmonic frequencies are mainly in the range of 0-30 MHz. The voltage distortion is more obvious during the fall of the pantograph. And the negative polarity spike pulse has a larger amplitude and occurs more frequently. The novelty of this paper lies in the experimental test with the high current and high power, as well as the systematic analysis of the electrical behaviors and multi-physical field evolution during the motion of the pantograph under the working conditions. Its contribution is to present an effective method to study the dynamic behaviors of the PAC. The research results can provide an important reference for the identification of the electrical characteristics of the PAC and the protection of the PAC equipment.

The electrified railways in mountainous areas are faced with multiple difficulties such as weak power grids, special climatic environments, complex and dangerous geographical conditions, which poses a great challenge to the reliable power supply of the traction power supply system (TPSS). In order to ensure that the overall reliability level of the TPSS meets the design requirements, this paper proposes a reliability allocation method for the TPSS of electrified railways in mountainous areas. Firstly, based on the characteristics of the interconnected power supply system of traction substation group (TSG) of the electrified railways in mountainous areas, the special topology of the TPSS, as well as the logical relationships between each power supply area and each equipment are sorted out. Secondly, the reliability allocation model of the interconnected power supply system of the TSG is established, and the reliability index of the system is allocated layer-by-layer from the whole system to the TSG according to the design requirements of the overall reliability level of the system. Finally, the reliability allocation model of the traction substation is established, and the reliability index is allocated to the underlying equipment of the traction substation, so as to clarify the reliability requirements of each power supply area and equipment. The results indicate that the reliability allocation results calculated by the proposed method can assist designers to be informed of the reliability objectives of each subsystem and power supply equipment, and can provide insights for related reliability design.

In the context of high-quality economic development in China, it is important to promote green innovation development by protecting intellectual property rights (IPR). Taking the pilot policy of the intellectual property courts in Beijing, Shanghai, and Guangzhou for example in a quasi-natural experiment, this article examines the effect of IPR protection on the development of corporate green innovation and its mechanisms by using a difference-in-differences model and a mediating effect model based on Chinese enterprise data from 2011 to 2019. The study found that first, IPR protection promotes enterprise green technological innovation; second, IPR protection affects green innovation through enterprise financing constraints and R&D investment; that is, increasing enterprise R&D investment and alleviating enterprise financing constraints are two important channels through which IPR protection promotes enterprise green technological innovation.

Abstract Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were −6.7% (SE 0.7) with mazdutide 3 mg, −10.4% (0.7) with 4.5 mg, −11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from −7.7% to −12.3% (all p

IntroductionThe efficient utilization of straw resources as animal feed has gained considerable attention. The objective of this study was to evaluate whether Lentinus sajor-caju treatment alters the chemical composition and antioxidant activity of highland barley straw and enhances its functional value as a ruminant feed.MethodsThe chemical composition, antioxidant capacity, and metabolomic profile of highland barley straw were determined after 21 days of solid-state fermentation with L. sajor-caju at 25°C. The differential metabolites between fermented and unfermented highland barley straw were identified by LC–MS and the relationship between the identified metabolites and antioxidant capacity was elucidated.ResultsThe results showed that, compared with untreated highland barley straw, the crude protein and ether extract contents were higher (51.55 and 76.43%, respectively) in highland barley straw after 21 days of incubation with L. sajor-caju, whereas the hemicellulose, cellulose, and acid detergent lignin contents were lower (2.48, 25.08, and 45%, respectively). The total antioxidant capacity was significantly higher in L. sajor-caju-treated than in untreated highland barley straw. In total, 600 differential metabolites (301 upregulated and 299 downregulated) were identified between L. sajor-caju-fermented and unfermented highland barley straw. Correlation analysis results showed that Fe2+ scavenging and total phenolic content were strongly correlated with total antioxidant capacity. Meanwhile, the differential flavonoid metabolites between fermented and unfermented highland barley straw were primarily associated with antioxidant activity, with kaempferol 3-xylosylglucoside, isoginkgetin, and rhoifolin being the most representative.ConclusionThus, this study demonstrates that L. sajor-caju could enhance the functional value of highland barley straw, showing the potential of L. sajor-caju for improving the utilization of agricultural straws in ruminants.

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-β-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.

Radiation therapy (RT) is currently the main clinical treatment of tumors. Before treatment initiation, precise delineation of the planned target volume (PTV) and organs at risk (OAR) is essential. This segmentation, together with the dose prediction algorithm, aids in the calculation and evaluation of the dose distribution, and ultimately in the refinement of the treatment plan. To provide a comprehensive view of the current landscape of research on dose prediction methods, we meticulously collected and summarized papers published between 2017 and 2023. First, we present our rigorous literature search approach, providing a statistical analysis of the pooled papers and an elaborate overview of the evaluation metrics that are commonly and consistently employed in this domain. Then, we focus on a detailed survey of the evolutionary trajectories of dose prediction methods. This comprehensive investigation covers a spectrum ranging from traditional Knowledge-Based Planning (KBP) methods to emerging deep learning-based methods, which include input improvement methods, U-Net-based methods, GAN-based methods, and other deep learning-based methods. Throughout this exposition, we have carefully outlined the strengths and limitations inherent in these various approaches. Finally, we conclude with a summary of the primary challenges facing the field and propose several prospective research directions to effectively address them.

Serious arc erosion is the main reason for premature failure of the Ag-matrix composite electrical contact materials in actual service. Clarifying the structure and property degradation process is crucial for creating eco-friendly Ag/MAX electrical contacts and upgrading high-performance materials for low-voltage switch applications. In this study, the representative Ag/Ti2AlC electrical contacts were designed into three arc erosion stages (from 1 to 5610 cycles) by ex-situ arc discharging experiment, and the nanoindentation technique was then applied to in-depth analyze the evolution behavior of nano-mechanical properties by comparing nano hardness, modulus, creep, continuous stiffness, elastic/plastic deformation, and NanoBlitz 3D Mapping indentation results in different erosion stages. Finally, the inherent relationship among the structural dissociation of Ti2AlC, and compositional changes of Ag/Ti2AlC interface and nano-mechanical properties of composite was revealed, and the material degradation model and anti-arc erosion mechanism were proposed. This work further elucidates the intrinsic source of excellent arc erosion resistance and degradation process of Ag/Ti2AlC composite from the nano-mechanical perspective and lays a theoretical foundation for the future design and optimization of this material system.

Abstract Background This study aimed to investigate the utilization patterns and factors related to oral health care for 5-year-old preschoolers based on Andersen’s Behavioural Model in Guizhou Province, Western China. Method A cross-sectional study of 4,862 5-year-old preschoolers in 66 kindergartens was conducted in 2019 and 2020. A basic oral examination and a survey of parents and grandparents were conducted to gather data on oral health services. The results were analysed using chi-square tests and logistic regression analysis. Result The utilization rate of oral health services for children in Guizhou province was 20.5%. The dmft was 4.43, and the rate of caries was 72.2%. The average cost of a dental visit was higher in rural areas and higher for girls. Logistic regression analysis revealed that dmft ≥ 6 teeth, a history of toothache, starting toothbrushing at age ≤ 3 years and limited parental knowledge were the primary factors impacting dental visits. Conclusion Needs factors such as severe oral conditions and pain in children are the main reasons for the utilization of these services. This study underscores the urgency to actively promote the importance of oral health and expand insurance coverage for oral health services.

The frequent occurrence of the pantograph–catenary (PC) arc seriously threatens the safe and stable operation of electric multiple units (EMUs). In order to investigate the primary factors affecting the electrical characteristics of the PC arc, this paper first reveals the mechanism of arc generation when EMUs leave the split-zone insulator according to the actual mechanical structure of the PC articulated split-zone insulator. Then, based on the Habedank black box arc model, considering the dynamic changes in arc length during the actual operation of EMUs, a numerical simulation model suitable for describing the PC articulated split-zone insulator arc is established. Furthermore, by comparing with existing research results, the effectiveness of the proposed model is verified. Next, a series of simulation experiments were conducted to analyze the influence of different operating parameters of the EMUs on the electrical characteristics of the PC arc. More importantly, the paper proposes using the entropy weight method to calculate the impact strength of different operating parameters of the EMUs on the arc duration time of the contact wire split-zone region. The research results of this paper can provide some technical references for reducing the erosion of the PC contact wire and slide caused by arcs when the EMUs pass through the split-zone insulator.

The fatigue behaviors of high-strength bearing steel were investigated with rotating bending fatigue loading with a frequency of 52.5 Hz. It was revealed that the high-strength steel tended to initiate at interior non-metallic inclusions in a very high-cycle fatigue regime. During fractography observation, it was also seen that the inclusion acting as a failure-originating site was seldom smaller than 10 μm. Moreover, prior austenite grains could also act as the originating source of failure when inclusion was absent. The crystal plasticity finite element method (CPFEM) was adopted to simulate the residual stress distribution around non-metallic inclusions of different sizes under different loading amplitudes. The accumulated plastic strain around the inclusion suggested that the existence of inclusion may reduce material strength and lead to more fatigue damage. The value of accumulated plastic strain around different inclusion sizes also resembled the crack nucleation or propagation of the materials. The simulation results also indicated that inclusions smaller than 5 μm had little influence on fatigue lifetimes, while inclusions larger than 10 μm had a significant influence on fatigue lifetimes.

The effective vibration area includes most of the catenary vibration caused by pantograph–catenary interactions and is the basis of the real-time catenary model for hardware-in-the-loop simulation. However, while the length of the effective vibration area is one of the most important parameters of the real-time catenary model, it has not been fully studied at present. In this paper, the length of the effective vibration area is first investigated. A pantograph–catenary interaction model is developed based on the modal superposition method. After the validation of the model, the vibration energy distribution of the catenary is used to determine the length of the effective vibration area based on the converged total energy. The influence of vehicle velocity and contact wire tension on the vibration energy distribution and length of the effective vibration area is investigated. The obtained appropriate length of effective vibration area is validated by a real-time catenary model and online measurement data of the contact force. The investigation results show that the energy distribution of the catenary can accurately determine the length of effective vibration area, and it increases with increasing vehicle velocity but decreases with increasing contact wire tension. The appropriate length of effective vibration area should be at least 160 m (approximately three spans) in the pantograph–catenary system.

The advancement of the big data industry is playing a pivotal role in urban land management refinement. Recently, China initiated a big data strategy, establishing national big data comprehensive pilot zones (NBDCPZs) across diverse regions. These initiatives present substantial opportunities for enhancing the urban land green use efficiency (ULGUE). Consequently, in this study, we utilized the super-efficiency slack-based measure (SBM) model with undesirable outputs to assess the ULGUEs across 281 prefecture-level cities in China from 2006 to 2021. Subsequently, leveraging the NBDCPZ establishment as a quasi-natural experiment, we employed the difference-in-differences (DID) method to empirically explore the impact of the NBDCPZ policy on the ULGUE for the first time. The findings revealed the following: (1) The implementation of the NBDCPZ policy significantly enhances the ULGUE; (2) the effects are mediated through mechanisms such as fostering technological innovation, mitigating resource misallocation, and promoting industrial agglomeration; (3) the heterogeneity analysis emphasizes the increased policy effectiveness in cities characterized by fewer natural resources, lower economic growth pressures, stable development stages, and moderate digital infrastructure and human capital levels; and (4) further analysis demonstrates the significant positive spillover effects of the NBDCPZ policy on the ULGUEs of neighboring non-pilot cities, with a diminishing impact as the proximity between pilot and non-pilot cities decreases. Overall, this study contributes to the literature on the relationship between the digital economy and land utilization, offering valuable insights for achieving sustainable urban development.

Abstract Background Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods A cross-sectional analysis of data from 3602 participants in the 2009–2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). Results There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). Conclusion Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Abstract Background Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging. Results Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment. Conclusion Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

Abstract The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U‐300, degludec U‐100, glargine U‐100, detemir, and insulin protamine Hagedorn) in insulin‐naïve adult patients with type 2 diabetes in the Asia‐Pacific region. Based on evidence from a systematic review, we developed an Asia‐Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second‐round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia‐Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.

Abstract Background Mitochondrial metabolism has been proposed as an attractive target for breast cancer therapy. The discovery of new mechanisms underlying mitochondrial dysfunction will facilitate the development of new metabolic inhibitors to improve the clinical treatment of breast cancer patients. DYNLT1 (Dynein Light Chain Tctex-Type 1) is a key component of the motor complex that transports cellular cargo along microtubules in the cell, but whether and how DYNLT1 affects mitochondrial metabolism and breast cancer has not been reported. Methods The expression levels of DYNLT1 were analyzed in clinical samples and a panel of cell lines. The role of DYNLT1 in breast cancer development was investigated using in vivo mouse models and in vitro cell assays, including CCK-8, plate cloning and transwell assay. The role of DYNLT1 in regulating mitochondrial metabolism in breast cancer development is examined by measuring mitochondrial membrane potential and ATP levels. To investigate the underlying molecular mechanism, many methods, including but not limited to Co-IP and ubiquitination assay were used. Results First, we found that DYNLT1 was upregulated in breast tumors, especially in ER + and TNBC subtypes. DYNLT1 promotes the proliferation, migration, invasion and mitochondrial metabolism in breast cancer cells in vitro and breast tumor development in vivo. DYNLT1 colocalizes with voltage-dependent anion channel 1 (VDAC1) on mitochondria to regulate key metabolic and energy functions. Mechanistically, DYNLT1 stabilizes the voltage-dependent anion channel 1 (VDAC1) by hindering E3 ligase Parkin-mediated VDAC1 ubiquitination and degradation. Conclusion Our data demonstrate that DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting Parkin-mediated ubiquitination degradation of VDAC1. This study suggests that mitochondrial metabolism can be exploited by targeting the DYNLT1-Parkin-VDAC1 axis to improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC).

The transverse resistivity anomaly with a hump feature, associated with topological magnetic textures, is of paramount importance for the applications of next-generation chiral spintronic devices. However, the origin of the hump feature still remains debated due to the complicated mechanism, not merely assigned to the intrinsic topological Hall effect (THE). In this work, we observe the apparent transverse resistivity hump characteristic superimposed on the Hall signals in AgNbO3/SrRuO3 (ANO/SRO) heterostructures. The intrinsic THE is ruled out by minor-loop and current density measurements. Combining the microscopic characterization and the two-channel anomalous Hall effect fitting, the hump feature is unambiguously attributed to the synergetic contribution from the SRO layer and the interfacial intermixing thin layer of ANO and SRO.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a dynamic chronic liver disease closely related to metabolic abnormalities such as diabetes and obesity. MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). However, the mechanisms underlying the progression of MASLD and further progression to liver fibrosis and liver cancer are unknown. Methods: In this study, we performed transcriptome analysis in livers from mice with MASLD and found suppression of a potential anti-oncogene, RAS association domain protein 4 (RASSF4). RASSF4 expression levels were measured in liver or tumor tissues of patients with MASH or HCC, respectively. We established RASSF4 overexpression and knockout mouse models. The effects of RASSF4 were evaluated by quantitative polymerase chain reaction, Western blotting, histopathological analysis, wound healing assays, Transwell assays, EdU incorporation assays, colony formation assays, sorafenib sensitivity assays, and tumorigenesis assays. Results: RASSF4 was significantly down-regulated in MASH and HCC samples. Using liver-specific RASSF4 knockout mice, we demonstrated that loss of hepatic RASSF4 exacerbated hepatic steatosis and fibrosis. In contrast, RASSF4 overexpression prevented steatosis in MASLD mice. In addition, RASSF4 in hepatocytes suppressed the activation of hepatic stellate cells (HSCs) by reducing transforming growth factor beta secretion. Moreover, we found that RASSF4 is an independent prognostic factor for HCC. Mechanistically, we found that RASSF4 in the liver interacts with MST1 to inhibit YAP nuclear translocation through the Hippo pathway. Conclusions: These findings establish RASSF4 as a therapeutic target for MASLD and HCC.

Wheel flat can seriously affect the wheel–rail contact performance and cause impact vibrations, which significantly threaten the safe operation of railway vehicles. It is crucial to accurately assess the effects of wheel flats on the wheel–rail contact performance and the vibration impact on the traction drive system. However, studies related to wheel flats have focused on the mechanical part and have yet to fully consider the electrical and mechanical parts of the entire traction drive system. Therefore, this paper first builds an electromechanical coupling model based on the electric traction drive system and the locomotive-track coupling dynamics model. Then, based on this model, the impact of the wheel flat on the electrical and mechanical parts of the traction drive system under different flat lengths, different flat depths, and different vehicle speeds was analyzed. The results indicate that with the increasing depth of the flat spot, the wheel–rail dynamic response, motor rotor speed, and motor torque exhibit more significant fluctuations. Additionally, as the locomotive speed increases, the impact of the flat on the wheel–rail contact performance intensifies. Wheel flats can excite the 1st bending mode of the wheelset, resulting in vibration shocks at 90 Hz.

Dropper failure seriously threatens the operation safety of a high-speed railway. In this work, for a simple chain suspension catenary, one span with five droppers is performed to establish a model and thus the effects of the moving load speed on dropper stress are investigated. First, the partial differential vibration equation of dropper is obtained through the mechanical analysis and converted into the finite difference equation. Then, we consider contact line as a beam element to obtain its motion equation. Furthermore, the boundary and initial conditions of five droppers are determined. Finally, the stresses of five droppers are numerically calculated and the effects of the moving load speed on dropper stress are investigated by writing a MATLAB code. The results suggest that the dropper location significantly affects its stress. Compared with other droppers, droppers II and IV have much more severe vibration amplitudes. Different moving load speeds could cause different stress change of each dropper. With the increasing speed, dropper experiences longer bending compression stage and the bending amplitude increases. The impact of the moving load speed on dropper stress is significant.

BackgroundDementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. ObjectiveBased on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. MethodsCN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer’s Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. ResultsExcept for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P

ContextSeveral observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified.ObjectiveThe aim of the study was to examine the causality of such associations by a Mendelian randomization study.MethodsTwo-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR–Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy.ResultsInverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (β= 9.059926, se= 1.762903, P = 2.76E-07 and β= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (β= 8.427943, se= 2.142493, P = 8.36E-05 and β= 3.100939, se= 0.74956, P=3.52E-05, respectively).ConclusionsThe study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.

Straw return can improve rice eating quality by modifying starch formation from long-term field trials, whereas the relevant mechanisms are still unknown. A long-term field experiment, including straw removal (CK), straw burning return (SBR), and straw return (SR) was conducted to investigate the starch structure, physicochemical properties, and cooked rice textures of indica early- and late-rice. Compared with CK, SBR and SR enhanced relative crystallinity, amylopectin long chains in both rice seasons, and gelatinization temperatures in late rice. Compared to SBR, SR decreased protein content and amylopectin short chains but increased starch branching degree, breakdown, and stickiness, ultimately contributing to improved starch thermal and pasting properties. Meanwhile, SR decreased hardness, cohesiveness, and chewiness, resulting in cooked texture meliorated, which was mainly attributed to amylopectin chain length and starch granule size. The results suggest that SR increased cooked texture of indica rice by altering starch structural and physicochemical properties.

Abstract Aims To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin‐naïve patients with type 2 diabetes mellitus. Methods MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO. Results Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta‐analyses and network meta‐analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U‐300 or degludec U‐100, glargine U‐100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U‐100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin

Abstract IoT is one of the fastest-growing technologies and it is estimated that more than a billion devices would be utilised across the globe by the end of 2030. To maximise the capability of these connected entities, trust and reputation among IoT entities is essential. Several trust management models have been proposed in the IoT environment; however, these schemes have not fully addressed the IoT devices’ features, such as device’s role, device type and its dynamic behavior in a smart environment. As a result, traditional trust and reputation models are insufficient to tackle these characteristics and uncertainty risks while connecting nodes to the network. Whilst continuous study has been carried out and various articles suggest promising solutions in constrained environments, research on trust and reputation is still at its infancy. In this paper, we carry out a comprehensive literature review on state-of-the-art research on the trust and reputation of IoT devices and systems. Specifically, we first propose a new structure, namely a new taxonomy, to organise the trust and reputation models based on the ways trust is managed. The proposed taxonomy comprises of traditional trust management-based systems and artificial intelligence-based systems, and combine both the classes which encourage the existing schemes to adapt these emerging concepts. This collaboration between the conventional mathematical and the advanced ML models result in design schemes that are more robust and efficient. Then we drill down to compare and analyse the methods and applications of these systems based on community-accepted performance metrics,e.g. scalability, delay, cooperativeness and efficiency. Finally, built upon the findings of the analysis, we identify and discuss open research issues and challenges, and further speculate and point out future research directions.

The impact of population aging on economic growth is a very important issue in the process of population structure change. This paper first proposes research hypotheses based on a systematic literature review and theoretical analysis of the negative and positive effects of population aging on economic growth. Then, based on the data of 30 provinces in the Chinese Mainland from 2000 to 2019, this paper empirically tests the impact of population aging on economic growth and its impact mechanism using a static panel data model, a dynamic panel data model and a mediating effect model. Our empirical analysis leads to the following conclusions. First, population aging has a significant inhibitory effect on economic growth. Second, the industrial structure upgrading plays a mediating role in the process of population aging affecting economic growth; that is, population aging inhibits economic growth by affecting the overall upgrading of the industrial structure as well as the industrial rationalization and optimization. Last, some policy implications are proposed based on the research conclusions.

Climate warming is a critical environmental issue affecting rice production. However, its effects on cooked rice texture and rice thermal properties remain unstudied in China. To address this gap, we conducted a two-year multi-site field warming experiment using free-air temperature increase facilities across three major Chinese rice cropping systems. Interestingly, warming had a minimal impact on the hardness of cooked rice, while it significantly increased stickiness by an average of 16.3% under warming conditions. Moreover, compared to control treatments, rice flour exhibited a significant increase in gelatinization enthalpy, onset, peak, and conclusion temperatures under warming conditions, with average increments of 8.7%, 1.00 °C, 1.05 °C, and 1.17 °C, respectively. In addition, warming significantly declined the amylose content, remarkedly elevated the protein content and relative crystallinity, and altered the weight distribution of the debranched starch. Correlation analysis revealed significant relationships between cooked rice stickiness, rice flour thermal properties, amylose content, protein content, and partial starch structures. Therefore, warming-induced alterations in rice composition and starch structure collectively enhanced cooked rice stickiness and rice thermal stability.

AimIt was the aim of this study to assess static postural control characteristics in people with type 2 diabetes mellitus (T2D) of different ages using a force platform. A relationship was also established between static postural control parameters and age in this study.MethodsA total of 706 participants with T2D were included in this study. The participants were stratified into three age groups: Group 1 (70 years old). Static postural control assessment during two-leg stance was performed on a force platform by all participants. The center of pressure (CoP)-related parameters were measured under two stance conditions (eyes open and closed). Kruskal–Wallis tests were applied to explore the difference among the different age groups. Multivariate regression analysis was performed to determine the relation between age and static postural control parameters.ResultsGroup 1 (70 years old). Group 1 (70 years old). There was a significantly positive correlation between age and the most static postural parameters such as CoP TTL, SA, MSL-X, MSL-Y, and V-Y. There was a significantly negative correlation between age and TTL/SA.ConclusionThis study suggested that older T2D participants had worse static postural control ability than younger ones. Most static postural parameters presented a significant correlation with age; the higher the age, the worse the static postural control.

Abstract Background Semantic segmentation of brain tumors plays a critical role in clinical treatment, especially for three-dimensional (3D) magnetic resonance imaging, which is often used in clinical practice. Automatic segmentation of the 3D structure of brain tumors can quickly help physicians understand the properties of tumors, such as the shape and size, thus improving the efficiency of preoperative planning and the odds of successful surgery. In past decades, 3D convolutional neural networks (CNNs) have dominated automatic segmentation methods for 3D medical images, and these network structures have achieved good results. However, to reduce the number of neural network parameters, practitioners ensure that the size of convolutional kernels in 3D convolutional operations generally does not exceed $$7 \times 7 \times 7$$ 7 × 7 × 7 , which also leads to CNNs showing limitations in learning long-distance dependent information. Vision Transformer (ViT) is very good at learning long-distance dependent information in images, but it suffers from the problems of many parameters. What’s worse, the ViT cannot learn local dependency information in the previous layers under the condition of insufficient data. However, in the image segmentation task, being able to learn this local dependency information in the previous layers makes a big impact on the performance of the model. Methods This paper proposes the Swin Unet3D model, which represents voxel segmentation on medical images as a sequence-to-sequence prediction. The feature extraction sub-module in the model is designed as a parallel structure of Convolution and ViT so that all layers of the model are able to adequately learn both global and local dependency information in the image. Results On the validation dataset of Brats2021, our proposed model achieves dice coefficients of 0.840, 0.874, and 0.911 on the ET channel, TC channel, and WT channel, respectively. On the validation dataset of Brats2018, our model achieves dice coefficients of 0.716, 0.761, and 0.874 on the corresponding channels, respectively. Conclusion We propose a new segmentation model that combines the advantages of Vision Transformer and Convolution and achieves a better balance between the number of model parameters and segmentation accuracy. The code can be found at https://github.com/1152545264/SwinUnet3D .

Abstract Water chestnut is a characteristic aquatic vegetable in China, and its demand for peeling fresh fruit is increasing rapidly. Aiming at the existing problems of high labor intensity and low efficiency of manual peeling, a combined water chestnut peeling machine was designed, which used a rotary knife to remove bud and root, and a differential friction belts to remove side peel. The performance of the peeling machine was tested with water chestnut from Xiaogan, Hubei Provence. Under the conditions of 200 g feeding mass and 10 r/min rotation speed, the single factor test was carried out with cutting speed as the influencing factor and the cutting rate of bud and root as the evaluation index. The results showed that the cutting rate of fresh fruit of water chestnut bud and root were 79.04% and 83.77% respectively when the cutting speed of rotary knife was 1.2 m/s. In the differential friction belts, high and low linear velocities were taken as the influencing factors, and the side peel removal rate was used as the evaluation index. The side peel removal rate was 84.93% at the high-speed linear velocity of 2.1 m/s and the low-speed linear velocity of 1.58 m/s. The performance of the whole machine was evaluated, and the results showed that the working loss of the combined water chestnut peeling machine was 43.03% and the comprehensive peeling rate was 77.43%, which reached the design requirements. This study can provide a reference for the research and development of water chestnut peeling device.

Diagnosis of bile duct cancer often occur in advanced stages, leading to poor survival. Here, the authors combine light scattering and diffuse reflectance spectroscopies in a minimally invasive endoscopic technique for directly assessing the malignant potential of the bile duct lining, and demonstrate 97% detection accuracy.

Abstract Background This study utilized bioinformatics to analyze the underlying biological mechanisms involved in adipogenic differentiation, synthesis of the extracellular matrix (ECM), and angiogenesis during preadipocyte differentiation in human Simpson–Golabi–Behmel syndrome at different time points and identify targets that can potentially improve fat graft survival. Results We analyzed two expression profiles from the Gene Expression Omnibus and identified differentially expressed genes (DEGs) at six different time points after the initiation of preadipocyte differentiation. Related pathways were identified using Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis (GSEA). We further constructed a protein–protein interaction (PPI) network and its central genes. The results showed that upregulated DEGs were involved in cell differentiation, lipid metabolism, and other cellular activities, while downregulated DEGs were associated with angiogenesis and development, ECM tissue synthesis, and intercellular and intertissue adhesion. GSEA provided a more comprehensive basis, including participation in and positive regulation of key pathways of cell metabolic differentiation, such as the “peroxisome proliferator-activated receptor signaling pathway” and the “adenylate-activated protein kinase signaling pathway,” a key pathway that negatively regulates pro-angiogenic development, ECM synthesis, and adhesion. Conclusions We identified the top 20 hub genes in the PPI network, including genes involved in cell differentiation, ECM synthesis, and angiogenesis development, providing potential targets to improve the long-term survival rate of fat grafts. Additionally, we identified drugs that may interact with these targets to potentially improve fat graft survival.

Objectives To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL).Methods Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated.Results No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75–21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83–15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1–3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1–6).Conclusions For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.