Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

Lung cancer is one of the most lethal cancers, and the overall survival rate of lung cancer patients is very low. With the increasing research on lung cancer, the critical role of intestinal flora in lung cancer treatment has been gradually discovered. Among the various therapeutic approaches targeting the intestinal flora, fecal microbiota transplantation (FMT) is considered as a potential strategy to treat lung cancer by interfering with the homeostasis of the intestinal flora. FMT can improve the efficacy of lung cancer treatment and attenuate the side effects associated with immunotherapy, chemotherapy, and radiotherapy by remodeling the microbial composition, modulating the metabolites, and activating immune responses. The aim of this paper is to discuss the current status and potential mechanisms of FMT in lung cancer treatment, and to provide a new strategy for regulating the intestinal flora to enhance the prevention and treatment of lung cancer.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Objective: To investigate the correlation of emotional and behavioral problems with sleep problems in children with cerebral palsy, so as to provide reference for intervention of emotional and behavioral problems in children. Methods: A cross sectional survey was conducted, and 402 children aged 6-18 with cerebral palsy who were adopted by social welfare institutions in Guangzhou City from January 2023 to January 2024 were selected to investigate their full time nurses. The Parents Strengths and Difficulties Questionnaire (SDQ) was used to assess the emotional and behavioral problems of children with cerebral palsy, and the Children s Sleep Habits Questionnaire (CSHQ) was used to assess sleep problems. Multiple linear regression analysis was used to analyze the correlation between the sleep problem of children with cerebral palsy and the emotional and behavioral problems. Results: The prevalence of emotional and behavioral difficulties among children with cerebral palsy was 15.7%. The median sleep problem score of children with emotional and behavioral problems [37.0(36.0, 41.0)] was significantly higher than that of children without emotional and behavioral [35.0(34.0, 36.0)] ( Z =-5.74, P <0.01). The results of multiple linear regression analysis showed that after adjusting covariables such as age, gender, cerebral palsy classification, language retardation, visual impairment and epilepsy, the total sleep problem score of children with cerebral palsy was positively correlated with the total difficulty score ( β= 0.28, 95%CI =0.17-0.34, P <0.05). Conclusions Sleep problems in children with cerebral palsy are associated with emotional and behavioral difficulties. Understanding of the management of sleep problems in children with cerebral palsy should be enhanced to reduce the incidence of emotional and behavioral problems in children with cerebral palsy.

Objective:To investigate the effect of infusing different doses of graft cells on viral infections and survival after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 99 patients with hematological diseases who underwent allo-HSCT in Shanxi Bethune Hospital were retrospectively analysed.The proportion of mononuclear cells(MNC)was counted microscopically,the proportions and absolute counts of CD34+cells and lymphocyte subsets(including CD3+T,CD4+T,CD8+T,CD4+CD8+T,B,and NK cells)were detected by flow cytometry,and the infusion dose of each cell types was calculated.The patients were divided into high-dose group and low-dose group based on the median value of the infused cell dose.The effects of different doses of various graft cells on post-transplant viral infections(CMV,EBV,BKV)and survival were analyzed.Results:The low-dose MNC(＜7.97 × 108/kg)and high-dose CD4+CD8+T cell(≥3.02 × 106/kg)groups had a higher Epstein-Barr virus(EBV)infection rate(P=0.031;P=0.020).The high-dose CD34+cell group and low-dose CD3+T,CD8+T and natural killer(NK)cell groups showed a trend toward higher EBV infection rates,but the differences were not statitsically significant(P＞0.05).There was no significant difference in the rates of EBV infection between the high-dose and low-dose groups of CD4+T and B cells(P＞0.05).Multivariate analysis revealed that the doses of MNC and CD4+CD8+T cells in the graft were independent factors influencing EBV infection(P=0.023;P=0.016).The doses of cells in the graft showed no significant impact on CMV and BKV infection,or patient survival(P＞0.05).Conclusion:Infusing a lower dose of MNC and a higher dose of CD4+CD8+T cells increases the risk of EBV infection,but does not affect the survival outcome.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

The active ingredient of WINREVAIR,sotatercept-csrk,is a recombinant activin receptor ⅡA-Fc(ActRⅡA-Fc)fusion protein that improves pro-proliferation(ActRⅡA/Smad2/3-mediated)and anti-proliferation(BMPRⅡ/Smad 1/5/8-mediated)signals,thereby regulating vascular proliferation.In March 2024,WINREVAIR was approved by the U.S.Food and Drug Administration for the treatment of pulmonary arterial hypertension(PAH)in adults.Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84％.Common adverse drugreactions include headache,epistaxis,rash,etc.