Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Cortical Endplate Bone Density Measured by Novel Phantomless Quantitative Computed Tomography May Predict Cage Subsidence more Conveniently and Accurately.

OBJECTIVE: Previous studies have shown that bone mineral density (BMD) is a predictor of cage subsidence. Phantom-less quantitative computed tomography (PL-QCT) can measure volumetric bone mineral density (vBMD) of lumbar trabecular and cortical bone. The study of endplate vBMD (EP-vBMD) is important in predicting cage settlement after extreme lateral interbody fusion (XLIF). This study aimed to determine the risk factors for postoperative cage subsidence after XLIF, particularly focusing on the relationship between vBMD measured by automatic PL-QCT and cage subsidence. METHODS: Patients who underwent XLIF surgery from January 2018 to October 2020 with a minimum of 6 months of follow-up were retrospectively included. Cage subsidence was defined as >2 mm cage sinking on the adjacent endplate in follow-up imaging evaluation. Outcome measures were localized vBMDs included EP-vBMDs with different region of interest (ROI) heights measured by PL-QCT based on a customized muscle-fat algorithm. Shapiro-Wilk test, one-way ANOVA, Mann-Whitney test, Fisher exact test, univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were executed in this study. RESULTS: One hundred and thirteen levels of 78 patients were included in the analysis. The mean age was 65 ± 7.9 years for 11 males and 67 females. Cage subsidence occurred on 45 (39.8%) surgical levels. There was no significant difference in demographics, fused levels, or preoperative radiographic parameters. 1.25-mm EP-vBMD (0.991 [0.985,0.997], p = 0.004) and P-TB-vBMD (cage-positioned trabecular volumetric bone mineral density) (0.988 [0.977-0.999], p = 0.026) were cage-subsidence relevant according to univariate analysis. Low 1.25-mm EP-vBMD (0.992 [0.985, 0.999], p = 0.029) was an independent risk factor according to multifactorial analysis. CONCLUSION: Preoperative low EP-vBMD was an independent risk factor for postoperative cage subsidence after XLIF. EP-vBMD measured by most cortex-occupied ROI may be the optimal vBMD parameter for cage subsidence prediction.

Application of Entity-BERT model based on neuroscience and brain-like cognition in electronic medical record entity recognition.

Introduction: In the medical field, electronic medical records contain a large amount of textual information, and the unstructured nature of this information makes data extraction and analysis challenging. Therefore, automatic extraction of entity information from electronic medical records has become a significant issue in the healthcare domain. Methods: To address this problem, this paper proposes a deep learning-based entity information extraction model called Entity-BERT. The model aims to leverage the powerful feature extraction capabilities of deep learning and the pre-training language representation learning of BERT(Bidirectional Encoder Representations from Transformers), enabling it to automatically learn and recognize various entity types in medical electronic records, including medical terminologies, disease names, drug information, and more, providing more effective support for medical research and clinical practices. The Entity-BERT model utilizes a multi-layer neural network and cross-attention mechanism to process and fuse information at different levels and types, resembling the hierarchical and distributed processing of the human brain. Additionally, the model employs pre-trained language and sequence models to process and learn textual data, sharing similarities with the language processing and semantic understanding of the human brain. Furthermore, the Entity-BERT model can capture contextual information and long-term dependencies, combining the cross-attention mechanism to handle the complex and diverse language expressions in electronic medical records, resembling the information processing method of the human brain in many aspects. Additionally, exploring how to utilize competitive learning, adaptive regulation, and synaptic plasticity to optimize the model's prediction results, automatically adjust its parameters, and achieve adaptive learning and dynamic adjustments from the perspective of neuroscience and brain-like cognition is of interest. Results and discussion: Experimental results demonstrate that the Entity-BERT model achieves outstanding performance in entity recognition tasks within electronic medical records, surpassing other existing entity recognition models. This research not only provides more efficient and accurate natural language processing technology for the medical and health field but also introduces new ideas and directions for the design and optimization of deep learning models.

Performance evaluation of an AI-based preoperative planning software application for automatic selection of pedicle screws based on computed tomography images.

Introduction: Recent neurosurgical applications based on artificial intelligence (AI) have demonstrated its potential in surgical planning and anatomical measurement. We aimed to evaluate the performance of an AI planning software application on screw length/diameter selection and insertion accuracy in comparison with freehand surgery. Methods: A total of 45 patients with 208 pedicle screw placements on thoracolumbar segments were included in this analysis. The novel AI planning software was developed based on a deep learning model. AI-based pedicle screw placements were selected on the basis of preoperative computed tomography (CT) data, and freehand surgery screw placements were observed based on postoperative CT data. The performance of AI pedicle screw placements was evaluated on the components of screw length, diameter, and Gertzbein grade in comparison with the results achieved by freehand surgery. Results: Among 208 pedicle screw placements, the average screw length/diameters selected by the AI model and used in freehand surgery were 48.65 ± 5.99 mm/7.39 ± 0.42 mm and 44.78 ± 2.99 mm/6.1 ± 0.27 mm, respectively. Among AI screw placements, 85.1% were classified as Gertzbein Grade A (no cortical pedicle breach); among free-hand surgery placements, 64.9% were classified as Gertzbein Grade A. Conclusion: The novel AI planning software application could provide an accessible and safe pedicle screw placement strategy in comparison with traditional freehand pedicle screw placement strategies. The choices of pedicle screw dimensional parameters made by the model, including length and diameter, may provide potential inspiration for real clinical discretion.

[Near-infrared excited graphene oxide/silver nitrate/chitosan coating for improving antibacterial properties of titanium implants].

Objective: To design and construct a graphene oxide (GO)/silver nitrate (Ag3PO4)/chitosan (CS) composite coating for rapidly killing bacteria and preventing postoperative infection in implant surgery. Methods: GO/Ag3PO4 composites were prepared by ion exchange method, and CS and GO/Ag3PO4 composites were deposited on medical titanium (Ti) sheets successively. The morphology, physical image, photothermal and photocatalytic ability, antibacterial ability, and adhesion to the matrix of the materials were characterized. Results: The GO/Ag3PO4 composites were successfully prepared by ion exchange method and the heterogeneous structure of GO/Ag3PO4 was proved by morphology phase test. The heterogeneous structure formed by Ag3PO4 and GO reduced the band gap from 1.79 eV to 1.39 eV which could be excited by 808 nm near-infrared light. The photothermal and photocatalytic experiments proved that the GO/Ag3PO4/CS coating had excellent photothermal and photodynamic properties. In vitro antibacterial experiments showed that the antibacterial rate of the GO/Ag3PO4/CS composite coating against Staphylococcus aureus reached 99.81% after 20 minutes irradiation with 808 nm near-infrared light. At the same time, the composite coating had excellent light stability, which could provide stable and sustained antibacterial effect. Conclusion: GO/Ag3PO4/CS coating can be excited by 808 nm near infrared light to produce reactive oxygen species, which has excellent antibacterial activity under light.

Genomic and Transcriptional Profiles of Kelch-like (klhl) Gene Family in Polyploid Carassius Complex.

Genome duplication supplies raw genetic materials and has been thought to be essential for evolutionary innovation and ecological adaptation. Here, we select Kelch-like (klhl) genes to study the evolution of the duplicated genes in the polyploid Carassius complex, including amphidiploid C. auratus and amphitriploid C. gibelio. Phylogenetic, chromosomal location and read coverage analyses indicate that most of Carassius klhl genes exhibit a 2:1 relationship with zebrafish orthologs and confirm two rounds of polyploidy, an allotetraploidy followed by an autotriploidy, occurred during Carassius evolution. The lineage-specific expansion and biased retention/loss of klhl genes are also found in Carassius. Transcriptome analyses across eight adult tissues and seven embryogenesis stages reveal varied expression dominance and divergence between the two species. The expression of klhls in response to Carassius herpesvirus 2 infection shows different expression changes corresponding to distinct herpesvirus resistances in three C. gibelio gynogenetic clones. Finally, we find that most C. gibelio klhl genes possess three alleles except eight genes that have lost one or two alleles due to genome rearrangement. The allele expression bias is prosperous for Cgklhl genes and varies during embryogenesis owning to the sequential expression manner of the alleles. The current study provides global insights into the genomic and transcriptional evolution of duplicated genes in a given superfamily resulting from multiple rounds of polyploidization.

RNA helicase DEAD-box protein 5 alleviates nonalcoholic steatohepatitis progression via tethering TSC complex and suppressing mTORC1 signaling.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease and its progressive form, nonalcoholic steatohepatitis (NASH), are rapidly becoming the top causes of hepatocellular carcinoma (HCC). Currently, there are no approved therapies for the treatment of NASH. DEAD-box protein 5 (DDX5) plays important roles in different cellular processes. However, the precise role of DDX5 in NASH remains unclear. APPROACH AND RESULTS: DDX5 expression was downregulated in patients with NASH, mouse models with diet-induced NASH (high-fat diet [HFD], methionine- and choline-deficient diet, and choline-deficient HFD), mouse models with NASH-HCC (diethylnitrosamine with HFD), and palmitic acid-stimulated hepatocytes. Adeno-associated virus-mediated DDX5 overexpression ameliorates hepatic steatosis and inflammation, whereas its deletion worsens such pathology. The untargeted metabolomics analysis was carried out to investigate the mechanism of DDX5 in NASH and NASH-HCC, which suggested the regulatory effect of DDX5 on lipid metabolism. DDX5 inhibits mechanistic target of rapamycin complex 1 (mTORC1) activation by recruiting the tuberous sclerosis complex (TSC)1/2 complex to mTORC1, thus improving lipid metabolism and attenuating the NACHT-, leucine-rich-repeat (LRR)-, and pyrin domain (PYD)-containing protein 3  inflammasome activation. We further identified that the phytochemical compound hyperforcinol K directly interacted with DDX5 and prevented its ubiquitinated degradation mediated by ubiquitin ligase (E3) tripartite motif protein 5, thereby significantly reducing lipid accumulation and inflammation in a NASH mouse model. CONCLUSIONS: These findings provide mechanistic insight into the role of DDX5 in mTORC1 regulation and NASH progression, as well as suggest a number of targets and a promising lead compound for therapeutic interventions against NASH.

Endplate volumetric bone mineral density biomechanically matched interbody cage.

Disc degenerative problems affect the aging population, globally, and interbody fusion is a crucial surgical treatment. The interbody cage is the critical implant in interbody fusion surgery; however, its subsidence risk becomes a remarkable clinical complication. Cage subsidence is caused due to a mismatch of material properties between the bone and implant, specifically, the higher elastic modulus of the cage relative to that of the spinal segments, inducing subsidence. Our recent observation has demonstrated that endplate volumetric bone mineral density (EP-vBMD) measured through the greatest cortex-occupied 1.25-mm height region of interest, using automatic phantomless quantitative computed tomography scanning, could be an independent cage subsidence predictor and a tool for cage selection instruction. Porous design on the metallic cage is a trend in interbody fusion devices as it provides a solution to the subsidence problem. Moreover, the superior osseointegration effect of the metallic cage, like the titanium alloy cage, is retained. Patient-specific customization of porous metallic cages based on the greatest subsidence-related EP-vBMD may be a good modification for the cage design as it can achieve biomechanical matching with the contacting bone tissue. We proposed a novel perspective on porous metallic cages by customizing the elastic modulus of porous metallic cages by modifying its porosity according to endplate elastic modulus calculated from EP-vBMD. A three-grade porosity customization strategy was introduced, and direct porosity-modulus customization was also available depending on the patient's or doctor's discretion.

Diverse polycyclic polyprenylated acylphloroglucinols with anti-neuroinflammatory activity from Hypericum beanii.

A phytochemical investigation on the roots of Hypericum beanii resulted in the isolation of six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperberlones A-F, along with fourteen known analogues. The structural characterization of these compounds was carried out by analyzing the HRESIMS data, 1D and 2D NMR spectroscopic data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations. Hyperberlone A (1) was a caged PPAP with a rare tricyclo[4.3.1.03,8]decane carbon skeleton. It was deduced to be biosynthetically generated from hyperbeanol C (8) through key Paternò-Büchi reaction, radical cascade cyclizations, and retro-aldol reaction. Compounds 4, 6, 7, 9, 14, and 16 exhibited significant nitric oxide (NO) production inhibitory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values of 6.11-25.28 µM. Moreover, compound 4 significantly decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced BV-2 microglia, as well as the phosphorylation of JNK.

Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish.

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.

Oral delivery of decanoic acid conjugated plant protein shell incorporating hybrid nanosystem leverage intestinal absorption of polyphenols.

Polyphenols are potent antioxidants, but their poor oral bioavailability owing to intrinsic insolubility and low permeability significantly hampers their effectiveness for clinical translation. Herein, upper intestinal absorptive polymer-lipid hybrid nanoparticles (PLN) was designed by exploiting the lipidic core for drug encapsulation and the decanoic acid conjugated rapeseed protein as the biopolymeric shell for gastrointestinal stability, retention and permeability. Polyphenol ellagic acid loaded core-shell PLN (EA-PLN(C/S)) was characterized of favorable physicochemical properties in simulated gastric- and intestinal fluids, including high drug loading capacity, slow drug release and prolonged stability. In Caco-2 monolayers, the cellular transport of EA-PLN(C/S) involved dual-paracellular and endocytosis pathways. Compared to drug in suspension or lipidic core nanoparticles, orally administered EA-PLN(C/S) was retained longer and more permeable via the duodenum and jejunum of upper intestine, resulting in up to 5.3-fold and 1.4-fold enhancement in the extent of drug absorption and colonic accumulation, respectively. In an acute colitis murine model, EA-PLN(C/S) at 6 mg/kg low dose markedly reduced colonic lipid peroxidation in contrast to no antioxidant effect in other EA formulations. This work suggests that integration of engineered plant protein biopolymer with lipid nanoparticles created unique oral drug delivery systems enabling intestinal site-specific absorption for effective antioxidant therapeutics.

Advances in 3D bioprinting technology for functional corneal reconstruction and regeneration.

Corneal transplantation constitutes one of the major treatments in severe cases of corneal diseases. The lack of cornea donors as well as other limitations of corneal transplantation necessitate the development of artificial corneal substitutes. Biosynthetic cornea model using 3D printing technique is promising to generate artificial corneal structure that can resemble the structure of the native human cornea and is applicable for regenerative medicine. Research on bioprinting artificial cornea has raised interest into the wide range of materials and cells that can be utilized as bioinks for optimal clarity, biocompatibility, and tectonic strength. With continued advances in biomaterials science and printing technology, it is believed that bioprinted cornea will eventually achieve a level of clinical functionality and practicality as to replace donated corneal tissues, with their associated limitations such as limited or unsteady supply, and possible infectious disease transmission. Here, we review the literature on bioprinting strategies, 3D corneal modelling, material options, and cellularization strategies in relation to keratoprosthesis design. The progress, limitations and expectations of recent cases of 3D bioprinting of artifial cornea are discussed. An outlook on the rise of 3D bioprinting in corneal reconstruction and regeneration is provided.

Transcriptome profiling revealed the growth superiority of hybrid pufferfish derived from Takifugu obscurus ♀ × Takifugu rubripes ♂.

Hybridization is an efficient method to breed new strains of aquatic animals. In the present study, we produced a hybrid puffer by crossing female obscure puffer with male tiger puffer. The hybrid puffer could live in fresh water like obscure puffer and exhibited growth superiority. The averaged body weight of 4- and 6-month-old hybrid puffer were respectively 38.06% and 38.93% higher than that of obscure puffer. Then, we analyzed the underlying genetic basis for the growth advantage of hybrid puffer by comparative transcriptome analysis. A total number of 4264 and 1285 differentially expressed genes (DEGs) were respectively identified from pituitary and liver transcriptome profiles between hybrid puffer and obscure puffer. Comprehensive analysis showed that the DEGs related with cell proliferation and differentiation, and protein synthesis and export, specifically showed higher expression levels in hybrid puffer, such as "ECM-receptor interaction", "focal adhesion", "protein export" and "protein processing in endoplasmic reticulum". While the DEGs involved in gametogenesis and carbohydrate and energy metabolism highly expressed in obscure puffer, such as "oxidative phosphorylation", "citrate cycle", "progesterone-mediated oocyte maturation" and "oocyte meiosis". Furthermore, a series of candidate genes related to the growth superiority of hybrid puffer were identified, such as fn1a, ptprc, plcg2, igf1, tgfß1, bmp4, abl1, col1a2, col1a1a, and myl9a. These results will be beneficial to understand the molecular basis of growth superiority and helpful to the hybrid breeding of pufferfish.

Nanoparticulate Drug Delivery Strategies to Address Intestinal Cytochrome P450 CYP3A4 Metabolism towards Personalized Medicine.

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients' outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B12 targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability.

Current Biological Strategies to Enhance Surgical Treatment for Rotator Cuff Repair.

Rotator cuff tear is one of the most common shoulder problems encountered by orthopedic surgeons. Due to the slow healing process and high retear rate, rotator cuff tear has distressed millions of people all around the world every year, especially for the elderly and active athletes. This disease significantly impairs patients' motor ability and reduces their quality of life. Besides conservative treatment, open and arthroscopic surgery contributes a lot to accelerate the healing process of rotator cuff tear. Currently, there are many emerging novel treatment methods to promote rotator cuff repair. A variety of biological stimulus has been utilized in clinical practice. Among them, platelet-rich plasma, growth factors, stem cells, and exosomes are the most popular biologics in laboratory research and clinical trials. This review will focus on the biologics of bioaugmentation methods for rotator cuff repair and tendon healing, including platelet-rich plasma, growth factors, exosomes and stem cells, etc. Relevant studies are summarized in this review and future research perspectives are introduced.

Comparison of Vascular Morphometry in Jawbones and Long Bones: Micro-CT Study in a Rat Model Treated with Zoledronic Acid.

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

Comparative transcriptomic analysis reveals an association of gibel carp fatty liver with ferroptosis pathway.

BACKGROUND: Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic. METHODS: Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses. RESULTS: Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured. CONCLUSIONS: We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.

Diverse Polycyclic Polyprenylated Acylphloroglucinol Congeners with Anti-Nonalcoholic Steatohepatitis Activity from Hypericum forrestii.

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.