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Abstract Ultrawidefield fundus (UWF) images have a wide imaging range (200° of the retinal region), which offers the opportunity to show more information for ophthalmic diseases. Image quality assessment (IQA) is a prerequisite for applying UWF and is crucial for developing artificial intelligence-driven diagnosis and screening systems. Most image quality systems have been applied to the assessments of natural images, but whether these systems are suitable for evaluating the UWF image quality remains debatable. Additionally, existing IQA datasets only provide photographs of diabetic retinopathy (DR) patients and quality evaluation results applicable for natural image, neglecting patients’ clinical information. To address these issues, we established a real-world clinical practice ultra-widefield fundus images dataset, with 700 high-resolution UWF images and corresponding clinical information from six common fundus diseases and healthy volunteers. The image quality is annotated by three ophthalmologists based on the field of view, illumination, artifact, contrast, and overall quality. This dataset illustrates the distribution of UWF image quality across diseases in clinical practice, offering a foundation for developing effective IQA systems.

Abstract Parkinson’s disease (PD) is a prevalent type of neurodegenerative disorder. AVE0991, a non-peptide analogue of Ang-(1–7), by which the progression of PD has been discovered to be ameliorated, but the specific mechanism whereby AVE0991 modulates the progression of PD re-mains unclear. The mice overexpressing human α-syn (A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing hα-syn (A53T). The [18F] FDG-PET/CT method was employed to assess FDG uptake in human α-syn (A53T) overexpressing mice. Levels of lnc HOTAIRM1 and miR-223-3p were detected via qRT-PCR. Flow cytometry was deployed to assay cell apoptosis. Here, we found that AVE0991 improved behaviour disorders and decreased α-syn expression in the substantia nigra of mice with Parkinson’s disease. AVE0991 inhibited the apoptosis of dopaminergic neurons overexpressing hα-syn (A53T) via lncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Moreover, miR-223-3p level in peripheral blood was found negatively correlated with the α-syn. Our present study shows that the angiotensin-(1–7) analogue AVE0991 targeted at the HOTAIRM1/miR-223-3p axis to degrade α-synuclein in PD mice, and showed neuroprotection in vitro.

Abstract This study evaluated cone density (CD) in the macular region and assess macular perfusion in children with varying degrees of myopia. This was a prospective, cross-sectional, observational study. Children underwent confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT), and OCT angiography (OCTA) imaging. A built-in software was used to measure mean CD (cells/mm2), retinal vessel density, choriocapillaris perfusion area, and choroidal thickness (CT). The study included 140 eyes from children categorized into four groups: emmetropia (31 eyes), low myopia (44 eyes), moderate myopia (31 eyes), and high myopia (34 eyes). The high myopia group exhibited significantly lower macular CD than the emmetropia group (P

Utilizing transplanted human umbilical cord mesenchymal stem cells (HUMSCs) for cartilage defects yielded advanced tissue regeneration, but the underlying mechanism remain elucidated. Early after HUMSCs delivery to the defects, we observed substantial apoptosis. The released apoptotic vesicles (apoVs) of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment. ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs. Mechanistically, in macrophages, miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization. In MSCs, let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis. Consequently, a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix (DCM) scaffold effectively promoted the regeneration of osteochondral defects. Overall, new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study. Moreover, we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.

Glucose-dependent insulinotropic polypeptide receptor (GIPR) is one of the important targets of neuroendocrine tumors (NETs). In this study，a novel GIPR targeting probe 68Ga-DOTA-GIP(1-30)-F-02 was constructed through the module for automatic labeling. The labeling yield，radiochemical purity，and in vitro stability of this probe were investigated. The biodistribution in normal ICR mice and Micro-PET/CT imaging of PC12-hGIP tumor-bearing mouse models were studied. The results showed that the automatic method for 68Ga-DOTA-GIP(1-30)-F-02 preparation was simple and convenient with a good radiochemical yield of (65.32±1.57)%，high radiochemical purity (>99%)，and good in vitro stability. The results of biodistribution showed low uptakes of 68Ga-DOTA-GIP(1-30)-F-02 in normal tissues，mainly excreted through the renal urinary system. Micro-PET/CT imaging showed the uptake at the tumor site reached (6.51±1.03)%ID/g at 60 min post-injection which indicates good tumor imaging potentiality. The feasibility and specificity of the probe for GIPR-targeted imaging of neuroendocrine tumors were preliminarily demonstrated.

Articular cartilage injury (ACI) remains one of the key challenges in regenerative medicine, as current treatment strategies do not result in ideal regeneration of hyaline-like cartilage. Enhancing endogenous repair via microRNAs (miRNAs) shows promise as a regenerative therapy. miRNA-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid (tFNA)-based targeting miRNA codelivery system, named A-T-M, was used. With tFNAs as vehicles, miR-140 and miR-455 were connected to and modified on tFNAs, while Apt19S (a DNA aptamer targeting MSCs) was directly integrated into the nanocomplex. The relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding mechanisms. Interestingly, a synergistic effect between miR-140 and miR-455 was revealed. Furthermore, A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation. A-T-M provides a new perspective and strategy for the regeneration of articular cartilage, showing strong clinical application value in the future treatment of ACI.

Abstract Anxiety among pregnant women can significantly impact their overall well-being. However, the development of data-driven HCI interventions for this demographic is often hindered by data scarcity and collection challenges. In this study, we leverage the Empatica E4 wristband to gather physiological data from pregnant women in both resting and relaxed states. Additionally, we collect subjective reports on their anxiety levels. We integrate features from signals including Blood Volume Pulse (BVP), Skin Temperature (SKT), and Inter-Beat Interval (IBI). Employing a Support Vector Machine (SVM) algorithm, we construct a model capable of evaluating anxiety levels in pregnant women. Our model attains an emotion recognition accuracy of 69.3%, marking achievements in HCI technology tailored for this specific user group. Furthermore, we introduce conceptual ideas for biofeedback on maternal emotions and its interactive mechanism, shedding light on improved monitoring and timely intervention strategies to enhance the emotional health of pregnant women.

Abstract Controversies persist about the protective effects of vaccines against acute cardiovascular events. Using electronic medical records from hospitals and influenza vaccine administration data in Beijing, China, we studied individuals vaccinated between January 1, 2016, and December 31, 2018, who experienced at least one acute cardiovascular event within two years. A self-controlled case series design calculated the relative incidence (RI) and 95% confidence interval (CI) of acute cardiovascular events within one year after vaccination. Among 1647 participants (median age: 65 years, 38.43% female), the risk of events 29–365 days post-vaccination was 0.76 times the baseline level (RI: 0.76; 95% CI: 0.68–0.84). The protective effect was more pronounced in younger participants (P = 0.043) and those without cardiovascular history (P

Abstract Background Malnutrition is common in older patients with chronic heart failure (HF) and often accompanies a deterioration of their condition. The Controlling Nutritional Status (CONUT) score is used as an objective indicator to evaluate nutritional status, but relevant research in this area is limited. This study aimed to report the prevalence, clinical correlates, and outcomes of malnutrition in elder patients hospitalized with chronic HF. Methods A retrospective analysis was conducted on 165 eligible patients admitted to the Department of Cardiology at Huadong Hospital from January 2021 to December 2022. Patients were categorized based on their CONUT score into three groups: normal nutrition status, mild risk of malnutrition, and moderate to severe risk of malnutrition. The study examined the nutritional status of this population and its relationship with clinical outcomes. Results Findings revealed that malnutrition affected 82% of the older patients, with 28% experiencing moderate to severe risk. Poor nutritional scores were significantly associated with prolonged hospital stay, increased in-hospital mortality and all-cause mortality during readmissions within one year (P

Intelligent control of the hole-seeking process of a rock drilling rig boom is crucial for enhancing the accuracy and efficiency of rock drilling operations. The inverse kinematics solution (IKS) is the core of achieving precise and rapid hole-seeking control of the boom. However, existing analytical and numerical techniques are inadequate in fulfilling the accuracy and time efficiency requirements for IKS in complex drilling boom scenarios. Conventional neural network (NN) approaches heavily depend on labeled data comprising target borehole sets derived from the activities of each joint and forward kinematics. The distribution of drill endpoints generated by this data cannot cover the entire workspace, resulting in the low reliability of the solution. To overcome these challenges, this study introduces an unsupervised learning-based NN method for IKS emphasizing safety constraints. This innovative method differs from traditional approaches in that it does not depend on labeled data. Instead, it utilizes the desired end position of the drilling boom as the network input. The network generates an eight-dimensional joint vector, and the actual drill end pose is derived through forward kinematics calculations on this vector. Then, the difference between the actual and desired drill end poses is used as the optimization objective, driving the network updates through gradient descent. The advantage of this method lies in eliminating the need for complex joint label data required in supervised learning IKS and using the differences in drill end poses directly as optimization objectives, which helps improve the accuracy of IKS. Meanwhile, a critical innovation of this study is integrating a safety collision penalty into the objective function of the solution, ensuring that the network’s output for joint positions adheres to specific environmental limitations. If the actual distance falls below the safety threshold, penalty terms are incorporated into the objective function, allowing for the adjustment of weights to maintain a balance between the precision demands of hole drilling and the design requirements of the safety constraints. This method improves the accuracy of IKS and significantly reduces its collision rate. Experimental results reveal that the mean hole-seeking error obtained using this unsupervised learning-based method achieves a mean hole-seeking error of 5–7 mm in IKS, a significant improvement of approximately 70.72% over supervised learning methods. Moreover, introducing safety constraints has successfully reduced the collision rate in IKS solutions by 90.28% without sacrificing the accuracy of the solutions.

Abstract Background Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer’s dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [3H]1 and [11C]1. The PET imaging properties of [11C]1 in mice and baboon were investigated. [3H]1 was studied in Bmax measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [11C]iodomethane or [3H]iodomethane to produce [11C]1 and [3H]1, respectively. Ex vivo brain biodistribution of [11C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [3H]1 was performed in frozen sections using a standard saturation binding technique. Results Compound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [11C]1 was synthesized with high yield. [3H]1 was synthesized similarly (commercially). Biodistribution of [11C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [11C]1 was ~ 50% specific for CSF1R. PET/CT [11C]1 study in baboon revealed low brain uptake (0.36 SUV) of [11C]1. Autoradiography with [3H]1 gave significantly elevated Bmax values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter. Conclusions Compound 1 exhibits a high in vitro CSF1R binding affinity. [11C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood–brain barrier in baboon PET. [3H]1 specifically labels CSF1R in post-mortem human brain. The binding of [3H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects.

Abstract Background Studies have indicated a close association between genes linked to liquid–liquid phase separation (LLPS) and the progression of prostate cancer (PCa). However, the interplay among long non-coding RNAs (lncRNAs) linked to LLPS in PCa remains elusive. Therefore, we constructed a prediction model based on LLPS-related LncRNA in PCa to explore its relationship with the prognosis and drug treatment of PCa. Methods We obtained clinical and sequencing data from TCGA and LLPS genes from the Phase Separation Protein Database. By analyzing the differential expression of LLPS-related genes and lncRNAs in prostate cancer, and using Poisson correlation, we identified LLPS-related lncRNAs. Prognostic LLPS-lncRNAs were found through prognostic correlation analysis and included in a Cox model to compute regression coefficients. Patients were scored and divided into high- and low-risk groups. Independent prognostic factors were integrated into a prognostic nomogram with risk and Gleason scores. We also conducted drug sensitivity analyses, GSEA, and validated the impact of key lncRNAs through functional experiments. Results Our study identified five LLPS-associated lncRNAs that are of prognostic importance. And found notable disparities in biochemical recurrence rates and survival outcomes between these risk groups, with the low-risk cohort exhibiting superior prognostic indicators. Moreover, our prediction nomogram demonstrated robust predictive accuracy and significant clinical utility. Furthermore, our model exhibited promising capabilities in forecasting patient sensitivity to various conventional therapeutic drugs, thereby highlighting its potential in personalized treatment strategies. GSEA showed that these lncRNAs may influence PCa prognosis and sensitivity to therapeutic agents by affecting pathways such as cell cycle. Knockdown of AC009812.4 could inhibit the ability of PCa cells to proliferate, migrate and invade, and compare to paracancerous tissue, AC009812.4 in PCa tissue has significantly higher expression. Conclusion Our research uncovers the prognostic significance of lncRNAs associated with LLPS in PCa and established a model exhibiting excellent predictive accuracy for prognosis. Those lncRNAs may influence progress of PCa as well as sensitivity to therapy drugs through pathways such as cell cycle.

Abstract Hydrate formation in foam drainage gas recovery wells and the shut in accidents caused by plugging have become an important problem that restricts the safe production of natural gas. The blockage and accumulation of hydrates is a gradual problem. This research goes beyond predicting the formation of hydrates and delves deeper into examining the rate of hydrate formation and the degree of pipeline blockage at different wellbore locations. First, the temperature model, pressure model, multiphase flow model, and hydrate plugging model of hydrate formation process are established from the equations of mass conservation, energy conservation, and momentum conservation. Second, an iterative approach is employed to solve the model, with a maximum error of 6.86% in model validation. Finally, sensitivity analysis shows that wellhead temperature, wellhead pressure, and foam viscosity have different effects on hydrate formation, maximum plugging position, and plugging degree. At the same time, combined with the actual drainage and gas production process, and the characteristics of hydrate blockage, proposed hydrate prevention measures can be taken to achieve safe production of natural gas. The research results indicate that a decrease in temperature signifies an increase in undercooling, resulting in an accelerated rate of hydrate formation and an elevated risk of hydrate blockage. The decrease in wellhead pressure leads to a decrease in the rate of hydrate formation and an increase in production, which is beneficial for the hydrate prevention. However, larger pressure differences and gas production rates will put higher requirements on equipment such as well control devices. An increase in foam viscosity will lead to increased pressure, foam compression, reduced drainage capacity, and intensified hydrate generation. Therefore, foam viscosity should be kept as small as possible to keep the foam stable.

Abstract Objective We aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease. Methods We prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes. Results A total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26–43.90, P

This study aimed to evaluate the seroprevalence of Bordetella pertussis and persistence of antibodies following vaccination. We recruited 6060 healthy subjects from five provinces of China during 2017–2018. Serum IgG antibodies against pertussis toxin (anti-PT IgG) and filamentous hemagglutinin (anti-FHA IgG), and serum IgA antibodies against pertussis toxin (anti-PT IgA) were measured by ELISA. Geometric mean concentration (GMC), seropositivity rate, and recent infection rate were calculated. Among 0–6 years-olds, the anti-PT IgG, anti-PT IgA, and anti-FHA IgG GMCs were 6.4 IU/ml (95% CI 6.1–6.8), 2.8 IU/ml (95% CI 2.7–2.8), and 13.3 IU/ml (95% CI 12.4–14.2), respectively. The anti-PT IgG GMC increased in accordance with the primary vaccination series (4–6 months) and the toddler booster (18–24 months), but declined thereafter through to age 5 years [4.7 IU/ml (95% CI 4.2–5.4)]. The seropositivity rate of pertussis in >6 year-olds was 9.0% (95% CI 8.1–9.9) and the recent infection rate was 3.3% (95% CI, 2.7–3.8). Recent infection rate began to increase from 6 years of age, with peaks at 9, 20, 40, and ≥60 years of age. The anti-PT IgG GMCs of children aged 0–6 years who were vaccinated with DTaP, DTaP-IPV//PRP～T, and DTaP-Hib were 5.9 IU/ml (95% CI 5.6–6.3), 20.7 IU/ml (95% CI 15.6–27.8), and 11.7 IU/ml (95% CI 7.5–18.1) (p

This paper proposes a stochastic strategic bidding approach for a multi-energy microgrid (MEMG) to optimize its participation across electricity, thermal energy, and hydrogen markets. A MEMG powered entirely by renewable energy and integrating these three energy forms is designed using advanced energy conversion and storage technologies. A bi-level model is developed: in the upper level, the MEMG’s bidding strategies are optimized to maximize profits under operational constraints and market demands; in the lower level, detailed pricing mechanisms for each energy market are modeled, incorporating physical constraints and market competition. To address uncertainties in renewable energy generation, a chance-constrained approach is employed to mitigate potential market penalties. Moreover, a novel cost estimation method enables the MEMG to effectively price energy during trading. The bi-level problem is transformed into a tractable mixed-integer linear programming (MILP) problem using the Karush–Kuhn–Tucker conditions and linearization techniques. Numerical results show that the MEMG efficiently participates in multiple energy markets, reducing renewable energy curtailment and adjusting its trading strategies based on market conditions, thereby improving overall economic benefits.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median −12.12%, interquartile ranges (IQRs) −18.62 to −5.626) and creatine (median −46.91 μmol/L, IQR −64.70 to −29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03–25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

As an important load-bearing part of the automobile chassis, the subframe is connected to the body and suspension system, and it is of great significance to perform the research on subframe lightweighting to improve the ride comfort and handling stability of the automobile. In order to comprehensively reflect the influence of operating conditions on the subframe, and at the same time consider the performance requirements such as strength and modal, the lightweight design of the subframe was performed with the combination of multi-condition topology optimization and multi-objective optimization methods. A rigid-flexible coupled multibody dynamic model of the front suspension was constructed to extract the loads at each articulation point of the subframe under multiple working conditions. Furthermore, the subframe was optimized for multi-condition topology in combination with the compromise programing method. Subsequently, the subframe was reconstructed based on the topology optimization results and a radial basis function (RBF) neural network approximation model was constructed using the optimal Latin hypercube tests. Then, the NSGA-II algorithm was adopted for multi-objective optimization of the reconstructed subframe. The optimized front subframe satisfies the performance requirements with the first-order frequency increased by 4 Hz, a weight reduction of 2.5 kg, the lightweight rate reaches 9.1%.

Background:Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model.Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress.Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.

BackgroundChina is vigorously promoting the health management of chronic diseases and exploring digital active health management. However, as most medical information systems in China have been built separately, there is poor sharing of medical information. It is difficult to achieve interconnectivity among community residents’ self-testing information, community health care information, and hospital health information, and digital chronic disease management has not been widely applied in China. ObjectiveThis study aimed to build a digital health platform and improve the effectiveness of full-cycle management for community chronic diseases through digital active health management. MethodsThis was a single-arm pre-post intervention study involving the development and use of a digital health platform (2-year intervention; 2020 to 2022). The digital health platform included the “i Active Health” applet for residents and the active health information system (cardio-cerebrovascular disease risk management system) for medical teams. The digital active health management of chronic diseases involved creating health streets, providing internet-assisted full-cycle active health services for residents, implementing internet-based community management for hypertension and diabetes, and performing real-time quantitative assessment and hierarchical management of residents’ risks of cardio-cerebrovascular disease. After the 2-year intervention, management effectiveness was evaluated. ResultsWe constructed a digital health platform with interconnected health information and implemented a digital active health management model. After the intervention, the 2-way referral between community health care institutions and hospitals increased. Residents’ health literacy rate increased from 30.6% (3062/10,000) in 2020 to 49.9% (4992/10,000) in 2022, with improvements in health knowledge, health behavior, and health skills. Moreover, the risk of cardio-cerebrovascular disease decreased after the intervention. The community hypertension and diabetes standardized management rates increased from 59.6% (2124/3566) and 55.8% (670/1200) in 2020 to 75.0% (3212/4285) and 69.4% (1686/2430) in 2022, respectively. The control rates of blood pressure in patients with hypertension and blood sugar in patients with diabetes increased from 51.7% (1081/2091) and 42.0% (373/888) in 2020 to 81.2% (1698/2091) and 73.0% (648/888) in 2022, respectively. The intervention improved patients’ BMI, waist circumference, blood uric acid levels, and low-density lipoprotein cholesterol levels. The drug compliance rate of patients with hypertension and diabetes increased from 33.6% (703/2091) and 36.0% (320/888) in 2020 to 73.3% (1532/2091) and 75.8% (673/888) in 2022, respectively. The intervention greatly improved the diet behavior, exercise behavior, and drinking behavior of patients with hypertension and diabetes. ConclusionsOur digital health platform can effectively achieve the interconnection and exchange of different health information. The digital active health management carried out with the assistance of this platform improved the effectiveness of community chronic disease management. Thus, the platform is worth promoting and applying in practice.

Head pose estimation plays a crucial role in various applications, including human–machine interaction, autonomous driving systems, and 3D reconstruction. Current methods address the problem primarily from a 2D perspective, which limits the efficient utilization of 3D information. Herein, a novel approach, called pose orientation‐aware network (POANet), which leverages normal maps for orientation information embedding, providing abundant and robust head pose information, is introduced. POANet incorporates the axial signal perception module and the rotation matrix perception module, these lightweight modules make the approach achieve state‐of‐the‐art (SOTA) performance with few computational costs. This method can directly analyze various topological 3D data without extensive preprocessing. For depth images, POANet outperforms existing methods on the Biwi Kinect head pose dataset, reducing the mean absolute error (MAE) by ≈30% compared to the SOTA methods. POANet is the first method to perform rigid head registration in a landmark‐free manner. It also incorporates few‐shot learning capabilities and achieves an MAE of about 1° on the Headspace dataset. These features make POANet a superior alternative to traditional generalized Procrustes analysis for mesh data processing, offering enhanced convenience for human phenotype studies.

Background: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. Methods: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. Results: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. Conclusion: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.