Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Objective To explore the construction of heart preservation model of empty beating donor based on extracorporeal membrane oxygenation (ECMO). Methods From January 2022 to August 2023, 20 Guangxi Bama miniature pigs weighing 25-30 kg were selected, half male and half female. Under general anesthesia and heparinization, a midline thoracotomy was performed. The pericardium was cut after freeing the anterior and posterior vena cavae, and a perfusion needle was inserted near the brachiocephalic artery in the ascending aorta, connected to a blood collection bag to collect 500-600 mL of blood. The anterior and posterior vena cavae were ligated, the aorta was blocked and perfused with HTK solution to stop the heart beating. The superior and inferior vena cavae were cut off, the right pulmonary vein was decompressed, the aorta and left and right pulmonary arteries and veins were cut off, and the whole heart was removed. An ECMO device was used to continuously perfuse a cardioprotective solution mainly composed of oxygenated warm blood, maintaining the isolated pig heart beating for 8 hours, monitoring (once/hour) ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, inflammatory factors, myocardial enzymes, myoglobin, and troponin levels. Myocardial tissue was taken for hematoxylin-eosin (HE) staining to observe myocardial cell damage and evaluate the quality of heart preservation. Results Among the 20 isolated beating pig hearts, 17 successfully resumed beating, 3 experienced ventricular fibrillation, resuscitated after intracardiac electrical defibrillation, and all 20 pig hearts successfully beat for 8 hours. There was no statistical difference in ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, and inflammatory factors at each time point (P>0.05). There were statistical increases in myocardial enzymes, myoglobin, and troponin levels (P<0.05). HE staining results suggested that there was no severe myocardial damage. Conclusion ECMO technology can be used for pig heart preservation with good results, and this study provides experimental evidence for improving heart preservation research in clinical heart transplantation.

ObjectiveTo investigate the effect of repetitive peripheral magnetic stimulation (rPMS) combined with upper limb intelligent robotic training on muscle tension, motor function and cortical excitability in children with unilateral spastic cerebral palsy (USCP). MethodsFrom March, 2023 to December, 2024, 90 children with USCP admitted to Children's Hospital of Soochow University were selected and randomly divided into control group (n = 30), rPMS group (n = 30) and combined group (n = 30). The control group received conventional occupational therapy. The rPMS group received rPMS intervention followed by conventional occupational therapy. The combined group received rPMS followed by upper limb intelligent robot training, for four weeks. Before and after treatment, muscle tension of biceps brachii was assessed using the modified Ashworth Scale (MAS); upper limb motor function was evaluated using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and upper limb intelligent parameters; and cortical excitability was measured using transcranial magnetic stimulation (TMS), including resting motor threshold (RMT) and motor-evoked potential (MEP) amplitude of the affected hemisphere. ResultsAfter treatment, MAS grades improved in all groups (|Z| > 3.523, P < 0.001), and the improvement in the combined group was superior to that in the control group (P < 0.05). Significant intra-group (F > 65.21, P < 0.001), inter-group (F > 17.94, P < 0.001) and interaction effects (F > 5.36, P < 0.01) were observed in FMA-UE scores, upper limb intelligent parameters and TMS parameters. Post Hoc analysis showed that the combined group demonstrated significantly greater improvements in FMA-UE scores, upper limb intelligent parameters, and TMS parameters compared with both the control and rPMS groups (all P < 0.01). Except for FMA-UE scores, the rPMS group showed significantly greater improvements than the control group in upper limb intelligent parameters (mechanical feedback, trajectory, and range of motion) and TMS parameters (RMT and MEP amplitude) (P < 0.05). ConclusionrPMS combined with upper limb intelligent robotic training can reduce upper limb muscle tension, improve motor function, and enhance cortical excitability in children with USCP.

ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 （SAMP8） by regulating the expression of glycoprotein non-metastatic melanoma protein B （GPNMB）. Furthermore， it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease （AD）. MethodsIn experiment 1， 24 5-month-old SAMP8 mice were randomly and equally divided into the model group， and the low-， middle- and high-dose（0.59，1.18，2.36 g·kg^-1） Liuwei Dihuangwan groups. At the same time， six 5-month-old senescence accelerated mouse resistant 1 （SAMR1） mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol （Cort）， adrenocorticotropic hormone （ACTH） and urine 17-hydroxycorticosteroid （17-OHCS） levels were detected by enzyme-linked immunosorbent assay （ELISA）. The ultrastructure of hippocampal neurons was observed by transmission electron microscope （TEM）， and the expression levels of hippocampal GPNMB， a disintegrin and metalloproteinase 10 （ADAM10） and autophagy-related proteins were detected by Western blot. In experiment 2， 18 SAMP8 mice were randomly and equally divided into the model group， vector control group （Vector）， and GPNMB overexpression group （GPNMB^OE）. Lentiviral vectors were stereotactically injected into the brain （2 μL per side in the GPNMB^OE group）. Western blot was used to detect the expression of the above target proteins in the hippocampus； In Experiment 3， 24 SAMP8 mice were randomly and equally divided into the model group， Liuwei Dihuangwan group， Liuwei Dihuangwan+negative control （NC） group， and Liuwei Dihuangwan+GPNMB silencing group （shGPNMB）. Before drug treatment， the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus， respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group （P<0.01）. The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group （P<0.01）. Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group， mitochondria were dominant， and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups， a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group， the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group， the levels of serum Cort， ACTH， and urine 17-OHCS in the model group were substantially increased， while the expression of hippocampal ADAM10， Beclin1， and microtubule associated-protein light chain 3-Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased （P<0.05， P<0.01）. Compared with the model group， the serum Cort and ACTH levels in the low-， medium-， and high-dose Liuwei Dihuangwan groups were significantly reduced， while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ expression levels in the medium-， and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group， whereas the expression of p62 was significantly reduced （P<0.01）. The above indicators showed a progressive trend among the three groups. Compared with the model group， the GPNMB^OE group showed a significant increase in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ expression， and a significant decrease in p62 expression （P<0.01）. Compared with the model group， the expression of GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased， while the expression of p62 significantly decreased （P<0.01）. Compared with the Liuwei Dihuangwan group， the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ， and a significant increase in p62 expression （P<0.01）. ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Objective To explore the regularity of prescriptions for epidemic disease in Taiping Huimin Heji Ju Fang based on the latent structure model and association rules analysis,and to provide references for modern epidemic treatment.Methods Prescriptions for epidemic diseases were extracted from Taiping Huimin Heji Ju Fang.A high-frequency herb matrix(frequency≥10)was constructed,and high-frequency herbs were analyzed using MicrosoftExcel 2016,Lantern 5.0,and IBM SPSS Modeler 18.0 for efficacy classification,property/flavor/channel tropism statistics,latent structure modeling,and association rule analysis.Results Among the 200 collected herbal prescriptions,46 high-frequency medicinal materials were identified,such as licorice,fresh ginger,dried ginger,poriae,and ginseng.The top 3 drugs efficacy were tonifying deficiency,relieving surface and warming inner.The medicinal properties were mainly warm,and the medicinal flavors were pungent,bitter,and sweet.The meridian tropisms mainly included the spleen meridian,lung meridian and stomach meridian.The analysis of latent structure model suggested that there were 8 types of common symptoms of epidemic disease,such as wind evil attack exterior,wind-cold-dampness,wind-heat,excess-heat in triple energizer,dampness inhibits qi stagnation,yang deficiency,blockage and spleen-qi deficiency.Theanalysis of association rules obtained licorice-ephedra and licorice-atractylodes,which with a core of licorice medicine,and the 16 association rules such as dried ginger-cinnamon,pericarpium citri reticulatae-mangnolia officinalis and poriae-ginseng-atractylodes macrocephala after eliminating ginger,jujube and licorice.Conclusion Most of the medicines used in the treatment of epidemic diseases in Taiping Huimin Heji Ju Fang are pungent,bitter and dispelling evil,the treatment should follow the principle of dispelling evil,warming yang to dissipate cold,dispelling dampness,clearing heat and expelling fire,inducing resuscitation,supporting the right and supplementing deficiency,which embodies the treatment principle of dispelling evil and supporting right,and provides reference and ideas for the treatment of clinical diseases based on syndrome differentiation.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.