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Abstract Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P

Abstract Spinal cord injury (SCI) results in irreversible neurological impairment. After SCI, Ferritinophagy-induced free iron released from ferritin can lead to extensive lipid peroxidation and aggravate neurological damage. NRF2/HO-1 pathway is to endow cells with a protective effect against oxidative stress, and it plays an important role in the transcriptional activation of a series of antioxidant and detoxification genes. UAMC-3203 is a ferrostatin-1(Fer-1) analogue with better solubility and stability, which can more effectively inhibit ferroptosis after SCI. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with UAMC-3203. ELISA was employed to assess the impact of UAMC-3203 on inflammation-related factors, while immunofluorescence was utilized to investigate the influence of UAMC-3203 on neuronal count as well as the activation of astrocytes and microglia/macrophages. Malondialdehyde (MDA) were detected to reflect the level of oxidation products. Western blot analysis was used to measure the level of ferroptosis markers and the expression of NRF2/HO-1. Our findings demonstrate that UAMC-3203 inhibits the production of reactive oxygen species (ROS) and lipid peroxides, preventing ferroptosis and reducing neuronal degeneration. Additionally, UAMC-3203 suppresses astrocyte proliferation and microglia/macrophage activation, as well as the release of ferroptosis-related inflammatory factors. These combined effects contribute to the preservation of spinal cord tissue and the facilitation of motor function recovery. UAMC-3203 maybe inhibit ferroptosis after SCI to promote functional recovery.

Abstract Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.

Hepatitis B virus (HBV) infection was highly endemic in China, where the prevalence of HBsAg was 9.7% in 1992. Comprehensive strategies, including universal infant hepatitis B vaccination with emphasis on timely birth-dose and 3-dose coverage, dramatically reduced the mother-to-infant transmission and early childhood acquisition of HBV, resulting in estimated HBsAg prevalence rates of 5.6% and 0.1% in the general population and among children aged

Mitochondria can contact lipid droplets (LDs) to form peridroplet mitochondria (PDM) which trap fatty acids in LDs by providing ATP for triglyceride synthesis and prevent lipotoxicity. However, the role of PDM in metabolic dysfunction associated steatotic liver disease (MASLD) is not clear. Here, the features of PDM in dietary MASLD models with different severity in mice were explored. Electron microscope photographs show that LDs and mitochondria rarely come into contact with each other in normal liver. In mice fed with high-fat diet, PDM can be observed in the liver as early as the beginning of steatosis in hepatocytes. For the first time, we show that PDM in mouse liver varies with the severity of MASLD. PDM and cytosolic mitochondria were isolated from the liver tissue of MASLD and analyzed by quantitative proteomics. Compared with cytosolic mitochondria, PDM have enhanced mitochondrial respiration and ATP synthesis. Diethyldithiocarbamate (DDC) alleviates choline-deficient, L-amino acid–defined diet-induced MASLD, while increases PDM in the liver. Similarly, DDC promotes the contact of mitochondria-LDs in steatotic C3A cells in vitro. Meanwhile, DDC promotes triglyceride synthesis and improves mitochondrial dysfunction in MASLD. In addition, DDC upregulates perilipin 5 both in vivo and in vitro, which is considered as a key regulator in PDM formation. Knockout of perilipin 5 inhibits the contact of mitochondria-LDs induced by DDC in C3A cells. These results demonstrate that PDM might be associated with the progression of MASLD and the prevention of MASLD by DDC.

Abstract Spinal cord injury (SCI) is a serious condition that results in irreparable nerve damage and severe loss of motor or sensory function. Resveratrol (3,4′,5-trihy- droxystilbene) is a naturally occurring plant-based polyphenol that has demonstrated powerful antioxidative, anti-inflammatory, and anti-carcinogenic pharmaceutical properties in previous studies. In the central nervous system, it promotes neuronal recovery and protects residual function. However, the role of resveratrol in SCI recovery remains elusive. In this study, the potential mechanisms by which resveratrol affect SCI in rats were assessed by constructing a contusion model of SCI. Resveratrol was intraperitoneally administered to rats. Behavioral scores and electrophysiological examinations were performed to assess functional recovery. After magnetic resonance imaging and staining with hematoxylin and eosin (HE) and Luxor Fast Blue (LFB), tissue recovery was analyzed. Immunofluorescence with NeuN and glial fibrillary acidic protein (GFAP) was employed to evaluate neuronal survival and glial changes. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to examine apoptotic rates. Moreover, network pharmacology was performed to identify relevant pathways of resveratrol for the treatment of SCI. Lastly, ELISA was performed to detect the expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Our findings revealed that resveratrol dramatically improved the hindlimb locomotor function and their electrophysiological outcomes. Notably, lesion size was significantly reduced on magnetic resonance imaging. HE and LFB staining exposed increased sparseness of tissue and myelin. GFAP and NeuN immunofluorescence assays at the lesion site determined that resveratrol boosted neuronal survival and attenuated glial cell overgrowth. In addition, resveratrol reduced the density and number of TUNEL-positive cells in rats after injury. Additionally, gene ontology analysis revealed that the enriched differentially expressed protein was associated with the JNK/p38MAPK (c-jun N-terminal kinase/p38 mitogen-activated protein kinase) signaling pathway. Following resveratrol treatment, the expression levels of IL-1β, TNF-α, and IL-6 were decreased. In summary, the administration of resveratrol protects motor function and neuronal survival in rats after SCI. Furthermore, resveratrol exerts an anti-inflammatory effect by blocking the JNK/p38MAPK signaling pathway.

This study addresses the challenges of elaeagnus angustifolia disease detection in smart agriculture by developing a detection system that integrates advanced deep learning technologies, including Large Language Models (LLMs), Agricultural Knowledge Graphs (KGs), Graph Neural Networks (GNNs), representation learning, and neural-symbolic reasoning techniques. The system significantly enhances the accuracy and efficiency of disease detection through an innovative graph attention mechanism and optimized loss functions. Experimental results demonstrate that this system significantly outperforms traditional methods across key metrics such as precision, recall, and accuracy, with the graph attention mechanism excelling in all aspects, particularly achieving a precision of 0.94, a recall of 0.92, and an accuracy of 0.93. Furthermore, comparative experiments with various loss functions further validate the effectiveness of the graph attention loss mechanism in enhancing model performance. This research not only advances the application of deep learning in agricultural disease detection theoretically but also provides robust technological tools for disease management and decision support in actual agricultural production, showcasing broad application prospects and profound practical value.

Objectives: To evaluate the efficacy and image processing time of the dynamic contrast-enhanced MRI (DCE-MRI) exchange model in liver fibrosis staging and compare it to the efficacy of magnetic resonance elastography (MRE). Methods: The subjects were 45 patients with nonalcoholic fatty liver disease (NAFLD) who underwent MRE and DCE-MRI in our hospital. Liver biopsy results were available for all patients. Spearman rank correlation coefficients were used to compare the correlations among MRE, DCE-MRI and liver fibrosis parameters. Quantitative DCE-MRI parameters, MRE-derived liver stiffness measurement (LSM), and the results of a combined DCE-MRI + MRE logistic regression model were compared in terms of the area under the receiver operating characteristic curve (AUC). We also compared the scanning and postprocessing times of the MRE and DCE-MRI techniques. Results: The correlation coefficients between the following parameters of interest and liver fibrosis were as follows: capillary permeability–surface area product (PS; DCE-MRI parameter), −0.761; portal blood flow (Fp; DCE-MRI parameter), −0.754; MRE-LSM, 0.835. Some DCE-MRI parameters (PS, Fp) had slightly greater AUC values than MRE-LSM for diagnosing the presence or absence of liver fibrosis, and the combined model had the highest AUC value for all stages except F4, but there was no significant difference in the diagnostic efficacy of the DCE-MRI, MRE, and combined models for any stage of fibrosis. The average scanning times for MRE and DCE-MRI were 17 s and 330 s, respectively, and the average postprocessing times were 45.5 s and 342.7 s, respectively. Conclusions: In the absence of MRE equipment, DCE-MRI represents an alternative technique. However, MRE is a quicker and simpler method for assessing fibrosis than DCE-MRI in the clinic.

Background: Mildly elevated levels of transaminase and/or immunoglobulin G (IgG) are common in patients with primary biliary cholangitis (PBC). It is still unclear whether adding immunosuppressive therapy to ursodeoxycholic acid (UDCA) benefits those patients who are not fulfilling the diagnostic criteria of PBC with autoimmune hepatitis (AIH) features. Objectives: To assess the efficacy of adding immunosuppressive therapy to UDCA for patients with PBC and autoimmune phenomena but not fulfilling the diagnostic criteria of PBC with AIH features. Design: This is a retrospective–prospective cohort study in a tertiary medical center. Methods: Patients with PBC and autoimmune phenomena were defined by the elevation of IgG and/or transaminase but did not fulfill the diagnostic criteria of PBC with AIH features. We grouped these patients based on with and without add-on immunosuppressive therapy and balanced their baseline characteristics using inverse probability treatment weighting (IPTW). Results: A total of 652 patients with PBC and autoimmune phenomena were included, with a median follow-up of 4.08 years. After IPTW, the pseudo sample size in the add-on therapy and monotherapy groups was 558 and 655, respectively. After 1 year of observation, patients in the add-on therapy group had a higher biochemical response rate (normalization of transaminase and IgG levels) (49% versus 17%, p

In this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ1 − 42 aggregation. Notably, compounds 13 and 17d displayed potent drug − likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC50 = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC50 = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ1 − 42−induced SH − SY5Y damage, while maintaining low toxicity in SH − SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual − targeted candidates for treating AD.

Due to the complex pathological mechanisms of Alzheimer's disease (AD), its treatment remains a challenge. One of the major difficulties in treating AD is the difficulty for drugs to cross the blood–brain barrier (BBB). Low-intensity ultrasound (LIUS) is a novel type of ultrasound with neuromodulation function. It has been widely reported that LIUS combined with intravenous injection of microbubbles (MB) can effectively, safely, and reversibly open the BBB to achieve non-invasive targeted drug delivery. However, many studies have reported that LIUS combined with MB-mediated BBB opening (LIUS + MB-BBBO) can improve pathological deposition and cognitive impairment in AD patients and mice without delivering additional drugs. This article reviews the relevant research studies on LIUS + MB-BBBO in the treatment of AD, analyzes its potential mechanisms, and summarizes relevant ultrasound parameters.

Abstract Background Non-alcoholic steatohepatitis (NASH) had not yet been approved therapy. Electro-acupuncture (EA) has been reported to have potential efficacy. However, high-quality clinical evidence was still lacking. Methods NASH patients were randomized and allocated to either sham acupuncture (SA) or EA group in a 1:1 ratio, with the patient blinded. Each patient received 36 sessions of SA or EA treatment over 12 weeks, followed by additional 4 weeks. The primary outcome was the changes in relative liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Results A total of 60 patients were enrolled. From baseline to week 12, the reduction of relative liver fat content measured by MRI-PDFF in the EA group (− 33.6%, quantile range: − 52.9%, − 22.7%) was significantly more significant than that in the SA group (− 15.8%, quantile range: − 36.1%, − 2.7%) (p = 0.022). Furthermore, the EA group had more patients who achieved MRI-PDFF to 30% reduction at week 12 (53.3% vs. 25.9%, p = 0.035). EA treatment also significantly reduced body weight (− 3.0 vs. + 0.1 kg, p = 0.034) and BMI (− 1.5 vs. − 0.2 kg/m2, p = 0.013) at week 16. Except for AST (− 27.4 vs. − 16.2 U/L, p = 0.015), other biochemical varieties, including ALT, fasting-glucose, cholesterol, and triglyceride, showed no statistically significant difference. Both groups measured no significant changes in liver stiffness by magnetic resonance elastography (MRE). There were no serious adverse events in either group. Conclusions Twelve weeks of EA effectively and safely reduces relative liver fat content in NASH patients. Further multicenter randomized controlled studies are needed. Trial registration Chinese Clinical Trial Registry, ChiCTR2100046617. Registered 23 May 2021, http://www.chictr.org.cn/edit.aspx?pid=127023&htm=4

In order to develop a coarse grain steamed bread with good quality and low glycemic index (GI), taking the appearance, texture, palatability and taste of coarse grain steamed bread as evaluation indexes, the fuzzy mathematical sensory evaluation method was established to determine the best proportion of barley powder, soybean powder and chickpea powder by orthogonal test. Finally, glycemic index human body test was carried out on coarse grain steamed bread. The results showed that the best preparation conditions of coarse grain steamed bread raw materials were 69.7% high gluten wheat flour, 2% potato flour, 3% tartary buckwheat flour, 5% highland barley flour, 10% soybean flour, 8% chickpea flour, 1.5% mulberry leaf extract and 0.8% stachyose. At this time, the sensory evaluation score was 82.3 and the GI value was 50.48. Therefore, the developed product was a low-glycemic index coarse grain steamed bread with lower glycemic index value, which was more suitable for people with sugar control and chronic diseases such as diabetes.

Abstract Anti‐mitochondrial autoantibodies (AMAs) are highly specific for the diagnosis of primary biliary cholangitis (PBC) but are also occasionally found in other diseases. In the present study, we evaluated the incidence of and predictors for PBC development in AMA‐positive patients with other liver or non‐liver diseases at baseline. In this retrospective study, we screened patients who tested positive for AMA and/or anti‐mitochondrial M2 antibody (AMA‐M2) at Beijing Friendship Hospital, Capital Medical University, from October 2005 to January 2017. They were categorized by their diagnosis at the baseline as patients with PBC or non‐PBC cases. We followed up on the non‐PBC cases through telephone interviews and reviewing of medical records to obtain laboratory results and clinical outcomes. In total, 139 patients were AMA‐positive but did not fulfill the diagnostic criteria of PBC at baseline, including 51 patients with non‐PBC liver diseases and 88 cases with non‐liver diseases. The titers of AMA‐M2, alkaline phosphatase, gamma‐glutamyl transpeptidase, and immunoglobulin M were significantly higher in patients with PBC compared to those with non‐PBC liver diseases and non‐liver diseases. After a median follow‐up of 4.6 (interquartile range: 2.4–7.6) years, 4.3% (6 of 139) developed PBC, with an accumulative 5‐year incidence rate of 4.2%. None of the patients with non‐PBC liver diseases developed PBC, whereas the 5‐year incidence rate of PBC was 7.8% among 88 patients with non‐liver diseases. Lower alanine aminotransferase and higher immunoglobulin M were independent predictors for developing PBC. Conclusion: Our results suggest a low risk of developing PBC over time in AMA‐positive patients with other liver and non‐liver diseases.

Abstract Background and aims Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse. Methods We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse. Result Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse. Conclusion Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.

Abstract Backgrounds Hereditary hemochromatosis (HH) is mainly caused by homozygous p.C282Y mutations in HFE in the Caucasians. We recently reported non-HFE mutations constitute the major cause of HH in Chinese. However, there is still a relatively high proportion of cases with primary iron overload from unexplained causes. We aimed to explore novel non-HFE mutations in Chinese patients with primary iron overload. Methods Whole exome sequence was conducted to screen mutations in novel HH-related genes in the 9 cases with unexplained primary iron overload. Then the representative candidate genes were screened for mutations in another cohort of 18 HH cases. The biological function of the selected genes and variants were analyzed in vitro. Results Whole exome sequencing of 9 cases with unexplained primary iron overload identified 42 missense variants in 40 genes associated with iron metabolism pathway genes such as UBE2O p.K689R and PCSK7 p.R711W. Subsequent Sanger sequencing of the UBE2O and PCSK7 genes in the 27 cases with primary iron overload identified p.K689R in UBE2O, p.R711W and p.V143F in PCSK7 at frequency of 2/27,1/27 and 2/27 respectively. In vitro siRNA interference of UBE2O and PCSK7 resulted in down-regulated HAMP mRNA expression. Adenovirus generation of UBE2O p.K689R in cell lines resulted in increased expression of SMAD6 and SMAD7 and downregulation of p-SMAD1/5 and HAMP expression, and the reduction of hepcidin level. Conclusions Our study identified a series of novel candidate non-HFE mutations in Chinese patients with HH. These may provide insights into the genetic basis of unexplained primary iron overload.

ObjectiveEpimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models.MethodsThe active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein–protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology.ResultsA total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI’s effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI’s active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor.ConclusionEPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.

IntroductionAnterior cervical discectomy and fusion (ACDF) is a common operation for spinal surgery to treat a variety of cervical diseases. The postoperative infection rate of this procedure is extremely low, and adjacent segments are rarely involved. Tuberculosis (TB) is a common infectious disease that affects the spine in less than 1% of cases and is more common in the thoracolumbar and rarely cervical spine. Herein, for the first time, we report tuberculosis infection in adjacent segments after ACDF.Case presentationWe report a 50-year-old patient with cervical spondylotic myelopathy (CSM) who was discharged from the hospital after receiving ACDF at the C3/4 level. Two months later, he was admitted to the hospital with neck pain and found to be infected with tuberculosis in C4/5. After 4 months of anti-tuberculosis treatment, the vertebral body was fused.ConclusionAfter ACDF, the adjacent cervical vertebrae were infected with TB but the infection was limited. We believe that the special vertebral blood supply and postoperative secondary blood-borne infection may lead to the occurrence of extrapulmonary tuberculosis.

Abstract Background During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Results We found that spermatogenesis was restarted by transplanting FGSCs into Kit w/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kit w/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis. Conclusion This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

With the evolution of modern agriculture and precision farming, the efficient and accurate detection of crop diseases has emerged as a pivotal research focus. In this study, an interpretative high-precision rice disease detection method, integrating multisource data and transfer learning, is introduced. This approach harnesses diverse data types, including imagery, climatic conditions, and soil attributes, facilitating enriched information extraction and enhanced detection accuracy. The incorporation of transfer learning bestows the model with robust generalization capabilities, enabling rapid adaptation to varying agricultural environments. Moreover, the interpretability of the model ensures transparency in its decision-making processes, garnering trust for real-world applications. Experimental outcomes demonstrate superior performance of the proposed method on multiple datasets when juxtaposed against advanced deep learning models and traditional machine learning techniques. Collectively, this research offers a novel perspective and toolkit for agricultural disease detection, laying a solid foundation for the future advancement of agriculture.

Abstract Background Hereditary hemochromatosis (HH) is widely recognized and clinical manifestations of hemochromatosis-related (HFE-related) HH is well studied in European populations. Less is known about the clinical and laboratory characteristics of non-HFE related HH in Asian population. We aimed to explore the relationship between genotype and clinical phenotype in Chinese patients with non-HFE related hereditary hemochromatosis. Methods Peripheral blood samples and clinical data of patients with primary iron overload were collected from the China Registry of Genetic/Metabolic Liver Diseases. Sanger sequencing was performed in cases with primary iron overload, for 5 known HH related genes (HFE, HJV, HAMP, TFR2 and SLC40A1) and 2 novel iron homeostasis-related genes (DENND3 and SUGP2). The correlation of genotype and clinical phenotype in these patients was analyzed. Results Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%), including 8 pathogenic variants in HJV, 7 pathogenic variants in SLC40A1, 8 likely pathogenic variants in SUGP2 and 5 likely pathogenic variants in DENND3 cases. Among these 31 cases, 4 cases harbored homozygous variants, 2 cases harbored homozygous + heterozygous variants, 19 cases harbored heterozygous or combined heterozygous variants, and 6 cases harbored no any damaging variants. None of investigated cases carried damaging HAMP and TFR2 variants were found. 8 cases were classified as type 2A HH and 6 cases as type 4 HH, 10 cases as non-classical genotype, and 6 cases had no pathogenic variants from 31 cases. During the statistical analysis, we excluded one case (SLC40A1 IVS3 + 10delGTT + SUGP2 p. R639Q(homo)) with difficulty in grouping due to combined damaging variants. Cases with type 2A HH have an earlier age at diagnosis (p = 0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p = 0.01). Arthropathy was relatively rare in all groups. None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p = 0.011), cardiac involvement (p = 0.042), diabetes (p = 0.035) and hypogonadism (p = 0.020) was statistically significant in the four groups. However, due to the limited sample size, the pairwise comparison showed no significant difference. Conclusions This is the first comprehensive analysis about the gene variant spectrum and phenotypic aspects of non-HFE HH in China. The results will be useful to the identification, diagnosis and management of HH in China.

Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients.Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts.Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682–0.756) in the discovery cohort and 0.828 (95% CI: 0.788–0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084).Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.

Background: Three-dimensional facial soft tissue landmark prediction is an important tool in dentistry, for which several methods have been developed in recent years, including a deep learning algorithm which relies on converting 3D models into 2D maps, which results in the loss of information and precision. Methods: This study proposes a neural network architecture capable of directly predicting landmarks from a 3D facial soft tissue model. Firstly, the range of each organ is obtained by an object detection network. Secondly, the prediction networks obtain landmarks from the 3D models of different organs. Results: The mean error of this method in local experiments is 2.62±2.39, which is lower than that in other machine learning algorithms or geometric information algorithms. Additionally, over 72% of the mean error of test data falls within ±2.5 mm, and 100% falls within 3 mm. Moreover, this method can predict 32 landmarks, which is higher than any other machine learning-based algorithm. Conclusions: According to the results, the proposed method can precisely predict a large number of 3D facial soft tissue landmarks, which gives the feasibility of directly using 3D models for prediction.

Abstract Background Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients. Methods This prospective multicentre observational follow-up study will include 142 obese patients with NAFLD scheduled to undergo one of the following surgical procedures: sleeve gastrostomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The primary outcome is the complete remission rate of NAFLD one year postoperatively, which is defined by liver fat fraction

N6-methyladenosine (m6A) methylation modification is the most prevalent and abundant internal modification of eukaryotic mRNAs. Increasing evidence has shown that mRNA m6A plays important roles in the development of stem cells. However, to the best of our knowledge, no reports about the roles of mRNA m6A in mouse female germline stem cells (mFGSCs) have been published. In this study, we compared the genome-wide profiles of mRNA m6A methylation and DNA methylation between FGSCs and sandosinbred mice (SIM) embryo-derived thioguanine and ouabain-resistant (STO) cells. qRT-PCR revealed that the expression levels of mRNA m6A-related genes (Mettl3, Alkbh5, Ythdf1, Ythdf2, Ythdc1, and Ythdc2) in FGSCs were significantly higher than those in STO cells. m6A RNA immunoprecipitation sequencing (MeRIP-seq) data further showed that the unique m6A-methylated mRNAs in FGSCs and STO cells were related to cell population proliferation and somatic development, respectively. Additionally, knockdown of Ythdf1 inhibited FGSC self-renewal. Comparison of methylated DNA immunoprecipitation sequencing (MeDIP-seq) results between FGSCs and STO cells identified that DNA methylation contributed to FGSC proliferation by suppressing the somatic program. These results suggested that m6A regulated FGSC self-renewal possibly through m6A binding protein YTHDF1, and DNA methylation repressed somatic programs in FGSCs to maintain FGSC characteristics.

Hepatic inflammation contributes to the development of nonalcoholic steatohepatitis (NASH). Here, the authors show that a transfer of ex vivo generated CD4 derived double negative T cells can prevent the development and progression of NASH by suppression of inflammatory Th17 cells and M1 macrophages in mouse models.

New endoscopic approaches for the prevention of delayed bleeding (DB) after gastric endoscopic submucosal dissection (ESD) have been reported in recent years, and endoscopic delivery of biodegradable polymers for iatrogenic ulcer hemostasis and coverage has emerged as one of the most promising techniques for post-ESD management. However, the comparative efficacy of these techniques remains uncertain. We performed a systematic search of multiple databases up to May 2022 to identify studies reporting DB rates as outcomes in patients undergoing gastric ESD who were treated with subsequent endoscopic management, including endoscopic closure (clip-based methods and suturing), PGA sheet tissue shielding, and hemostatic powder/gel spray (including polymeric sealants and other adhesives). The risk ratios (RRs) of delayed bleeding in treatment groups and control groups were pooled, and the Bayesian framework was used to perform a network meta-analysis (NMA). Among these studies, 16 head-to-head comparisons that covered 2742 lesions were included in the NMA. Tissue shielding using PGA sheets significantly reduced the risk of DB by nearly two thirds in high-risk patients, while hemostatic spray systems, primarily polymer-based, reduced DB in low-risk patients nine-fold. Researchers should recognize the essential role of polymers in the management of ESD-induced ulcers, and develop and validate clinical application strategies for promising materials.

HFE-related Hemochromatosis is the most common genetic iron overload disease in European populations, particularly of Nordic or Celtic ancestry. It is reported that the HFE p.C282Y mutation is present in 1/10 people of northern European descent, resulting in one in two hundred people will be homozygous. However, the HFE p.C282Y heterozygosity is virtually absent among East Asians, including Japanese, Koreans, and Chinese. In this article, we report a case of HFE-related hemochromatosis caused by compound heterozygosity HFE p.C282Y/p.R71X. This is the first report of hemochromatosis associated with HFE p.C282Y mutation in China.

T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune checkpoint that regulates normal immune responses but can be exploited by tumor cells to evade immune surveillance. TIM-3 is primarily expressed on immune cells, particularly on dysfunctional and exhausted T cells, and engagement of TIM-3 with its ligands promotes TIM-3-mediated T cell inhibition. Antagonistic ligand-blocking anti-TIM-3 antibodies have the potential to abrogate T cell inhibition, activate antigen-specific T cells, and enhance anti-tumor immunity. Here we describe M6903, a fully human anti-TIM-3 antibody without effector function and with high affinity and selectivity to TIM-3. We demonstrate that M6903 blocks the binding of TIM-3 to three of its ligands, phosphatidylserine (PtdSer), carcinoembryonic antigen cell adhesion-related molecule 1 (CEACAM1), and galectin 9 (Gal-9). These results are supported by an atomic resolution crystal structure and functional assays, which demonstrate that M6903 monotherapy enhanced T cell activation. This activation was further enhanced by the combination of M6903 with bintrafusp alfa, a bifunctional fusion protein that simultaneously blocks the transforming growth factor-β (TGF-β) and programmed death ligand 1 (PD-L1) pathways. M6903 and bintrafusp alfa combination therapy also enhanced anti-tumor efficacy in huTIM-3 knock-in mice, relative to either monotherapy. These in vitro and in vivo data, along with favorable pharmacokinetics in marmoset monkeys, suggest that M6903 as a monotherapy warrants further pre-clinical assessment and that M6903 and bintrafusp alfa may be a promising combination therapy in the clinic.

ABSTRACT Background: primary biliary cholangitis (PBC) patients with a suboptimal response to ursodeoxycholic acid (UDCA) have a significantly worse survival rate. Fenofibrate has been shown to improve the short-term biochemical response in this group of patients. However, there is limited data available on the safety and efficacy of its long-term use, especially in patients with cirrhosis. Methods: in this retrospective cohort study, fenofibrate was given to PBC patients with a suboptimal response to at least 12 months of UDCA (13-15 mg/kg/d) therapy. Biochemistry data, GLOBE score and UK-PBC risk score at baseline and at different time points of treatment were compared. The safety profiles were also compared between cirrhotic and non-cirrhotic patient groups. Results: fenofibrate (200 mg/day) was given to 39 PBC patients with a suboptimal response to UDCA (15 cirrhotic and 24 non-cirrhotic patients). In the 26 patients who completed more than one year of combination therapy, the alkaline phosphatase (ALP) levels were 215 (185, 326) U/l, 122 (110, 202) U/l, 128 (106, 194) U/l, 124 (100, 181) U/l and 120 (82, 168) U/l, at baseline, three months, six months, 12 months and 24 months, respectively. All p values were < 0.01 when compared to baseline values. After two years of combination therapy, the UK-PBC risk score and GLOBE score did not significantly improve. The overall rates of adverse events were not significantly different between the cirrhotic and non-cirrhotic group. The elevation of liver enzymes was the most frequent side effect (n = 7), leading to a discontinuation in four patients. Furthermore, after two years of combination therapy, the serum creatinine levels and estimated glomerular filtration rates (eGFR) were significantly worse in both groups. Conclusion: fenofibrate add-on therapy could improve ALP and -GT levels in both non-cirrhotic and cirrhotic PBC patients with a suboptimal response to UDCA. However, patients need to be monitored carefully for a potential liver injury and nephrotoxicity.

Background/Aims: Dysfunctional autophagy has been reported to be associated with aberrant intestinal metabolism. Amino acids can regulate autophagic activity in intestinal epithelial cells (IECs). Na+/H+-exchanger 3 (NHE3) has been found to participate in the absorption of amino acids in the intestine, but whether NHE3 is involved in the regulation of autophagy in IECs is unclear. Methods: In the present study, an amino acid starvation-induced autophagic model was established. Then, the effects of alanine and proline with or without the NHE inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) were evaluated. Autophagy was examined based on the microtubule-associated light chain 3 (LC3) levels, transmission electron microscopy (TEM), tandem GFP-mCherry-LC3 construct, sequestosome-1 (SQSTM1, P62) mRNA and protein levels, and autophagy-related gene (ATG) 5, 7, and 12 expression levels. The autophagic flux was evaluated as the ratio of yellow (autophagosomes) to red (autolysosomes) LC3 puncta. Results: Following amino acid starvation, we found the LC3-II and ATG expression levels were enhanced in the IEC-18 cells. An increase in the number of autophagic vacuoles was concomitantly observed by TEM and confocal microscopy. Based on the results, supplementation with either alanine or proline depressed autophagy in the IEC-18 cells. Consistent with the elevated LC3-II levels, ATG expression increased upon NHE3 inhibition. Moreover, the mCherry-GFP-LC3 autophagic puncta representing both autophagosomes and autolysosomes per cell increased after EIPA treatment. Conclusions: These results demonstrate that NHE (most likely NHE3) may participate in the amino acid regulation of autophagy in IECs, which would aid in the design of better treatments for intestinal inflammation.

Gonadotropin-inhibitory hormone (GnIH) can decrease luteinizing hormone and/or follicle-stimulating hormone levels in rat, mouse, sheep, and cattle by the direct suppression of gonadotropin-releasing hormone (GnRH). The present study investigated polymorphisms in the GnIH genes of two dairy goat breeds and their association with litter size. Single nucleotide polymorphisms (SNPs) g.1837C>G and g.3195G>A (GenBank Accession Nos. KR778885 and KR819142) were detected in the GnIH genes of Xinong Saanen and Guanzhong dairy goat breeds using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Furthermore, the g.1837C>G and g.3195G>A loci were closely linked in both breeds (r2 > 0.33). Association analysis showed that these SNPs had significant effects on the litter size of goats (P < 0.05). In both breeds, individuals with the CC/GG (g.1837C>G/g.3195G>A) genotype showed larger litter sizes in the second and average parities than individuals with the GG/AA genotype (P < 0.05). Known biochemical and physiological functions, along with our results, indicate that the CC/GG genotype may be used in marker-assisted selection to choose individuals with a larger litter size from both breeds.

Abstract X-ray phase-contrast computed tomography (PCCT) can provide excellent image contrast for soft tissues with small density differences, and it is particularly appropriate for three-dimensional (3D) visualization of accurate microstructures inside biological samples. In this study, the morphological structures of proliferative bile ductules (BDs) were visualized without contrast agents via PCCT with liver fibrosis samples induced by bile duct ligation (BDL) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group, 2-week and 6-week post-BDL groups. All livers were removed after euthanasia for a subsequent imaging. The verification of the ductular structures captured by PCCT was achieved by a careful head-to-head comparison with their corresponding histological images. Our experimental results demonstrated that PCCT images corresponded very well to the proliferative BDs shown by histological staining using cytokeratin 19 (CK19). Furthermore, the 3D density of proliferative BDs increased with the progression of liver fibrosis. In addition, PCCT accurately revealed the architecture of proliferative BDs in a 3D fashion, including the ductular ramification, the elongation and tortuosity of the branches, and the corrugations of the luminal duct surface. Thus, the high-resolution PCCT technique can improve our understanding of the characteristics of ductular proliferation from a new 3D perspective.

Objectives: Liver macrophages agitated by Lipopolysaccharide (LPS) can enhance immuno-inflammatory responses in the liver which mediate liver injury and result in dysfunction. Midazolam has been reported to have inhibitory effects on activated immunity and escalated inflammation, however, what the effects of midazolam on the liver injury caused by excessive immuno-inflammatory response in sepsis, and what influence it will exert on inflamed liver macrophages need to be elucidated.Methods: In the present study, LPS and galactosamine-induced acute liver injury mice were used to observe the effect of midazolam in vivo. LPS-stimulated bone marrow cells were used to evaluate the influence of midazolam on monocytes in vitro.Results: Midazolam prevented liver tissue injury and decreased serum alanine transaminase (ALT) level in LPS plus galactosamine treated mice. Mechanistically, midazolam suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) produced by LPS stimulated liver macrophages in vivo and bone marrow monocytes in vitro, and reduced the expression of major histocompatibility complex class II (MHC II), cluster of differentiation 40 and 86 (CD40 and CD86) on the cell surface. These results could be reversed by PK-11195, a peripheral benzodiazepine receptor (PBR) blocker.Conclusion: Midazolam can prevent liver from LPS-induced immune mediated liver injury by inhibiting inflammation and immune activation in liver macrophages.

Summary: Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show that compared with WT mice, OX40−/− mice exhibit decreased liver fat accumulation, lobular inflammation, and focal necrosis after feeding with diets that induce NASH. Mechanistically, OX40 deficiency suppresses Th1 and Th17 differentiation, and OX40 deficiency in T cells inhibits monocyte migration, antigen presentation, and M1 polarization. Soluble OX40 stimulation alone upregulates antigen presentation, chemokine receptor expression, and proinflammatory cytokine secretion by liver monocytes. Furthermore, plasma soluble OX40 levels are positively associated with NASH in humans, suggesting clinical relevance of the findings. In conclusion, we show a mechanism for T cell regulation of innate immune cells. OX40 is a key regulator of both intrahepatic innate and adaptive immunity, generates two-way signals, and promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development. : Sun et al. show that OX40 is a key molecule in the regulation of both intrahepatic innate and adaptive immunity. OX40 promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development and progression. These findings suggest that OX40 could serve as a diagnostic index and therapeutic target in NASH. Keywords: OX40, NAFLD, inflammation, monocyte, T cell

Follicular atresia mainly results from the apoptosis of granulosa cells (GCs). Whilst our previous investigations examined the role of chi-miR-4110 in regulating ovarian function, the present study detected the role of chi-miR-4110 in GC development. We transfected caprine GCs cultured in vitro with chi-miR-4110 mimics. Results revealed that chi-miR-4110 decreased mRNA and protein levels of Smad2 by targeting its 3'-untranslated region (3'UTR). FoxC1 and Sp1 mRNA and protein levels markedly increased, whereas those of bHLHe22 significantly decreased (P

GRAS transcriptional factors have diverse functions in plant growth and development, and are named after the first three transcription factors, namely, GAI (GIBBERELLIC ACID INSENSITIVE), RGA (REPRESSOR OF GAI) and SCR (SCARECROW) identified in this family. Knowledge of the GRAS gene family in maize remains was largely unknown, and their characterization is necessary to understand their importance in the maize life cycle. This study identified 86 GRAS genes in maize, and further characterized with phylogenetics, gene structural analysis, genomic loci, and expression patterns. The 86 GRAS genes were divided into 8 groups (SCL3, HAM, LS, SCR, DELLA, SHR, PAT1 and LISCL) by phylogenetic analysis. Most of the maize GRAS genes contain one exon (80.23%) and closely related members in the phylogenetic tree had similar structure and motif composition. Different motifs especially in the N-terminus might be the sources of their functional divergence. Segmental- and tandem-duplication occurred in this family leading to expansion of maize GRAS genes and the expression patterns of the duplicated genes in the heat map according to the published microarray data were very similar. Quantitative RT-PCR (qRT-PCR) results demonstrated that the expression level of genes in different tissues were different, suggesting their differential roles in plant growth and development. The data set expands our knowledge to understanding the function of GRAS genes in maize, an important crop plant in the world.

BACKGROUND:[corrected] Hepatic fibrosis can lead to deformation of vessel morphology and structure. In the present feasibility study, high-resolution computed tomography (CT) using diffraction-enhanced imaging (DEI) was used to represent three-dimensional (3D) vessel microstructures of hepatic fibrosis in rats and to differentiate different stages of hepatic fibrosis using qualitative descriptions and quantitative measurement of microvessels. MATERIAL AND METHODS:Three typical specimens at different stages, i.e., mild, moderate and severe hepatic fibrosis, were imaged using DEI at 15 keV without contrast agents. The correspondence between DEI-CT images and histopathological findings was determined. The 3D visualizations from different stages of hepatic fibrosis were presented using DEI-CT. Additionally, Qualitative descriptions and quantitative evaluation of vessel features, such as vessel trend, vascular distortion deformation, thrombus formation and texture features on the inner wall of the vessel, were performed. RESULTS:DEI-CT produced high-resolution images of the vessel microstructures in hepatic fibrosis that corresponded to information on actual structures observed from the histological sections. Combined with the 3D visualization technique, DEI-CT enabled the acquisition of an accurate description of the 3D vessel morphology from different stages of hepatic fibrosis. Qualitative descriptions and quantitative assessment of microvessels demonstrated clear differences between the different stages of hepatic fibrosis. The thrombus inside the vessel of severe liver fibrosis was accurately displayed, and corresponding analysis can provide an exact measurement of vessel stenosis rate. CONCLUSIONS:DEI-CT may allow morphologic descriptions and quantitative evaluation of vessel microstructures from different stages of hepatic fibrosis and can better characterize the various stages of fibrosis progression using high-resolution 3D vessel morphology.

The peanut (Arachis hypogaea) is an important oil crop. Breeding for high oil content is becoming increasingly important. Wild Arachis species have been reported to harbor genes for many valuable traits that may enable the improvement of cultivated Arachis hypogaea, such as resistance to pests and disease. However, only limited information is available on variation in oil content. In the present study, a collection of 72 wild Arachis accessions representing 19 species and 3 cultivated peanut accessions were genotyped using 136 genome-wide SSR markers and phenotyped for oil content over three growing seasons. The wild Arachis accessions showed abundant diversity across the 19 species. A. duranensis exhibited the highest diversity, with a Shannon-Weaver diversity index of 0.35. A total of 129 unique alleles were detected in the species studied. A. rigonii exhibited the largest number of unique alleles (75), indicating that this species is highly differentiated. AMOVA and genetic distance analyses confirmed the genetic differentiation between the wild Arachis species. The majority of SSR alleles were detected exclusively in the wild species and not in A. hypogaea, indicating that directional selection or the hitchhiking effect has played an important role in the domestication of the cultivated peanut. The 75 accessions were grouped into three clusters based on population structure and phylogenic analysis, consistent with their taxonomic sections, species and genome types. A. villosa and A. batizocoi were grouped with A. hypogaea, suggesting the close relationship between these two diploid wild species and the cultivated peanut. Considerable phenotypic variation in oil content was observed among different sections and species. Nine alleles were identified as associated with oil content based on association analysis, of these, three alleles were associated with higher oil content but were absent in the cultivated peanut. The results demonstrated that there is great potential to increase the oil content in A. hypogaea by using the wild Arachis germplasm.