More resilient polyester membranes for high-performance reverse osmosis desalination.

Thin-film composite reverse osmosis membranes have remained the gold standard technology for desalination and water purification for nearly half a century. Polyamide films offer excellent water permeability and salt rejection but also suffer from poor chlorine resistance, high fouling propensity, and low boron rejection. We addressed these issues by molecularly designing a polyester thin-film composite reverse osmosis membrane using co-solvent-assisted interfacial polymerization to react 3,5-dihydroxy-4-methylbenzoic acid with trimesoyl chloride. This polyester membrane exhibits substantial water permeability, high rejection for sodium chloride and boron, and complete resistance toward chlorine. The ultrasmooth, low-energy surface of the membrane also prevents fouling and mineral scaling compared with polyamide membranes. These membranes could increasingly challenge polyamide membranes by further optimizing water-salt selectivity, offering a path to considerably reducing pretreatment steps in desalination.

Deep Reinforcement Learning for Solving Vehicle Routing Problems With Backhauls.

The vehicle routing problem with backhauls (VRPBs) is a challenging problem commonly studied in computer science and operations research. Featured by linehaul (or delivery) and backhaul (or pickup) customers, the VRPB has broad applications in real-world logistics. In this article, we propose a neural heuristic based on deep reinforcement learning (DRL) to solve the traditional and improved VRPB variants, with an encoder-decoder structured policy network trained to sequentially construct the routes for vehicles. Specifically, we first describe the VRPB based on a graph and cast the solution construction as a Markov decision process (MDP). Then, to identify the relationship among the nodes (i.e., linehaul and backhaul customers, and the depot), we design a two-stage attention-based encoder, including a self-attention and a heterogeneous attention for each stage, which could yield more informative representations of the nodes so as to deliver high-quality solutions. The evaluation on the two VRPB variants reveals that, our neural heuristic performs favorably against both the conventional and neural heuristic baselines on randomly generated instances and benchmark instances. Moreover, the trained policy network exhibits a desirable capability of generalization to various problem sizes and distributions.

LSTM-MSA: A Novel Deep Learning Model With Dual-Stage Attention Mechanisms Forearm EMG-Based Hand Gesture Recognition.

This paper introduces the Long Short-Term Memory with Dual-Stage Attention (LSTM-MSA) model, an approach for analyzing electromyography (EMG) signals. EMG signals are crucial in applications like prosthetic control, rehabilitation, and human-computer interaction, but they come with inherent challenges such as non-stationarity and noise. The LSTM-MSA model addresses these challenges by combining LSTM layers with attention mechanisms to effectively capture relevant signal features and accurately predict intended actions. Notable features of this model include dual-stage attention, end-to-end feature extraction and classification integration, and personalized training. Extensive evaluations across diverse datasets consistently demonstrate the LSTM-MSA's superiority in terms of F1 score, accuracy, recall, and precision. This research provides a model for real-world EMG signal applications, offering improved accuracy, robustness, and adaptability.

[Changes in Ozone Pollution Trend Characteristics and Sensitivity in Jinan from 2015 to 2020].

The surface ozone (O3) spatiotemporal distribution, variations, and its causes in Ji'nan from 2015 to 2020 were revealed based on the air quality monitoring network data and satellite retrievals from the Ozone Monitoring Instrument (OMI). The results showed that the ozone concentration in Ji'nan gradually increased from 2015 to 2020. The annual 90th percentile of the daily maximum 8-h average (MDA8) O3(namely the annual evaluation value) and the MDA8 O3(April-September) increased by 4.8 µg·(m3·a)-1 and 3.8 µg·(m3·a)-1, respectively. The trend of the ozone levels in the high-concentration range increased faster than that in the low-concentration range. The MDA8 in June increased by 7.4 µg·(m3·a)-1, and the rate range of increases was 2.6-3.9 µg·(m3·a)-1 in the cool seasons (December-February); thus, the O3 control in winter cannot be ignored. It is apparent from the diurnal variations in ozone from 2015 to 2020 in April-September that the average ozone levels have risen in recent years. The growth rate in the daytime was higher than that at night. The capacity of photochemical production has been increasing, especially in recent years. Additionally, it is noteworthy that the peak time for ozone levels occurred approximately 1-2 h earlier. The disparity of ozone concentrations among different stations gradually decreased in recent years. Compared with that in 2015, the range of areas with high O3 concentrations in 2019-2020 was further expanded. The significant positive trends in MDA8-90th and MDA8 (April-September) were observed in 16.1% and 22.6% of the monitoring sites in Ji'nan (P<0.05), most of which were located in urban areas and the suburbs close to urban areas. The temporal and spatial changes in ozone in Jinan had been affected by the changes in VOCs and NOx emissions since 2015. Satellite remote sensing data from 2015 to 2020 revealed that the NO2 tropospheric columns (April-September) showed reductions of 20.6%, with a decreasing rate of 0.3×1015 mole·(cm2·a)-1, especially in the urban areas and suburbs. The detected variation trends of tropospheric HCHO were weak and insignificant, which suggested that the decrease in NOx emissions was much greater than the decrease in VOCs emissions, and the gap had become more obvious in the urban areas. With responses to precursor emissions, the chemical sensitivity of O3 formation had been changing. The VOCs-limited regimes continuously decreased, and the mixed NOx/VOCs-sensitive regimes and NOx-limited regimes increased. In general, such an extremely inappropriate control ratio of ozone precursor NOx/VOCs led to an overall trend of slow increasing fluctuations of O3 in Ji'nan. The findings clearly indicate that the reduction of VOCs in Ji'nan was far from sufficient, and strengthening the current control of VOCs emissions is an effective measure to control the growth trend of O3 pollution in Ji'nan in the near future, especially in urban and surrounding suburban areas.

A comparative analysis of digital health usage intentions towards the adoption of virtual reality in telerehabilitation.

BACKGROUND: With the rapid development of the metaverse and the problem of non-attendance in traditional rehabilitation, virtual reality in telerehabilitation has become increasingly vital in modern medicine. However, research on determining predictors that influence the public's behavioral intention to adopt VR-based telerehabilitation has not been extensively studied. OBJECTIVE: This study aims to propose a new research model with a comparative analysis on understanding factors affecting the public's behavioral intention to adopt VR in telerehabilitation for different user groups. METHODS: A total of 215 respondents from the general public completed an online questionnaire to validate the proposed research model. The collected data was analyzed using SPSS and AMOS. The proposed model was additionally validated using CFA and multiple linear regression. RESULTS: This study found that effort expectancy, threat appraisals, and trust had a positive significant influence on the public's behavioral intention to adopt VR in telerehabilitation. However, performance expectancy and facilitating conditions had no significant relationship with behavioral intention. Notably, the average of the primary factors for older adults was generally higher than for younger adults. CONCLUSIONS: The present study confirms the applicability of the proposed research model. Our findings contribute up-to-date insights for related stakeholders to minimize implementation failures and develop successful adoption strategies for the future expansion of telerehabilitation.

[Experimental study of improved sclerotherapy injection in rat model of vertebral arteriocervical spondylopathy].

OBJECTIVE: To improve the rat model of cervical spondylosis of vertebral artery type (CSA) induced by injecting sclerosing agent. To evaluate the efficacy of injecting sclerosing agent to induce CSA. METHODS: Forty Health SPF SD rats(20 males and 20 females), were randomly divided into two groups:the model group (20) and the blank group (20). All the animals were followed up for 4 weeks for the observation of general situation, transcranial Doppler(TCD) detection of blood flow velocity, pulsatility index and resistive index of the vertebral artery, measurement of mental distress by open-field test. RESULTS: One to two days after establish the animal model, rats in the model group appeared apathetic with decreased autonomic activities, trembling, squinting, increased eye excrement, etc., and no rats died during the experiment. The mean blood flow velocity of the model group was lower than that of the blank group (P<0.05), and the pulsatilit index and resistive index of the model group were higher than that of the blank group (P<0.05). The mental distress of the model group was significantly higher than that of the blank group. CONCLUSION: The modified injection of sclerosing agent is a practical method to establish the rat model of CSA, with high success rate, high stability, low mortality and simple operation.

Feasibility of intelligent drug control in the maintenance phase of general anesthesia based on convolutional neural network.

Background: The growth and aging process of the human population has accelerated the increase in surgical procedures. Yet, the demand for increasing operations can be hardly met since the training of anesthesiologists is usually a long-term process. Closed-loop artificial intelligence (AI) model provides the possibility to solve intelligent decision-making for anesthesia auxiliary control and, as such, has allowed breakthroughs in closed-loop control of clinical practices in intensive care units (ICUs). However, applying an open-loop artificial intelligence algorithm to build up personalized medication for anesthesia still needs to be further explored. Currently, anesthesiologists have selected doses of intravenously pumped anesthetic drugs mainly based on the blood pressure and bispectral index (BIS), which can express the depth of anesthesia. Unfortunately, BIS cannot be monitored at some medical centers or operational procedures and only be regulated by blood pressure. As a result, here we aim to inaugurally explore the feasibility of a basic intelligent control system applied to drug delivery in the maintenance phase of general anesthesia, based on a convolutional neural network model with open-loop design, according to AI learning of existing anesthesia protocols. Methods: A convolutional neural network, combined with both sliding window sampling method and residual learning module, was utilized to establish an "AI anesthesiologist" model for intraoperative dosing of personalized anesthetic drugs (propofol and remifentanil). The fitting degree and difference in pumping dose decision, between the AI anesthesiologist and the clinical anesthesiologist, for these personalized anesthetic drugs were examined during the maintenance phase of anesthesia. Results: The medication level established by the "AI anesthesiologist" was comparable to that obtained by the clinical anesthesiologist during the maintenance phase of anesthesia. Conclusion: The application of an open-loop decision-making plan by convolutional neural network showed that intelligent anesthesia control is consistent with the actual anesthesia control, thus providing possibility for further evolution and optimization of auxiliary intelligent control of depth of anesthesia.

Clinical significance of LAG-3 on microvessel density in primary hepatocellular carcinoma.

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival. Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS). Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child-Pugh grade, and lymph node metastasis correlated with survival. Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.

[Differential Diagnosis of Three Commonest Deletion ß-Thalassemia in Chinese].

OBJECTIVE: To analyze the hematological characteristics of Chinese Gγ+(Aγδß)0-thalassemia，SEA-HPFH and Taiwan type ß-thalassemia. METHODS: Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samples，PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically. RESULTS: The 3 types of deletion ß- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type ß-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese Gγ+(Aγδß)0-thalassemia，the levels of Hb A2 in the other two deletion ß-thalassemia patients were significantly increased. Except for Hb, there were significant differences in MCV, MCH, Hb A2 and HbF between Chinese Gγ+(Aγδß)0-thalassemia and SEA-HPFH(P<0.001). CONCLUSION: Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion ß-thalassemia in Chinese.

[Genetic Effect Analysis of ß-globin Gene 3'UTR+101G>C (HBB:c. *233G>C) Variant].

OBJECTIVE: To investigate whether ß-globin gene 3'UTR+101G>C (HBB:c.*233G>C) variant has genetic effect and provide basis for gene diagnosis and genetic counseling. METHOD: Whole blood cell analysis and capillary zone electrophoresis (CZE) were used to analyze the hematological indexes. The most frequent 23 mutations in southern Chinese individuals were routinely measured by PCR-flow fluorenscence immunmicrobeads assay. Sanger sequencing was used to detect the other variants of ß-globin gene (HBB). RESULTS: In 463 cases, a total of 7 cases with HBB:c.*233G>C variant were detected, among them 4 cases carried other pathogenic variants of HBB gene (2 cases were in trans, 2 cases were in cis), who had typical hematological characteristics of mild ß-thalassemia, and 3 cases also carried abnormal hemoglobin variation, but did not have hematological characteristics of ß-thalassemia. CONCLUSION: The study shows that HBB:c.*233G > C variant has no obvious genetic effect and should be a benign polymorphism.

L-leucine promotes axonal outgrowth and regeneration via mTOR activation.

Discovering safe and effective drugs that promote neuron regeneration is an essential strategy for the recovery of central nervous system injuries. In this study, we found that L-leucine, an essential amino acid obtained from both supplements and food sources, could dramatically boost axonal outgrowth and regeneration. First, the effects of L-leucine on neurons were evaluated by cell apoptosis, survival, and death assays, and the results showed no changes in these processes after treatment. By live cell imaging, L-leucine was found to remarkably increase axonal length and growth velocity after axotomy. We also verified that L-leucine enhanced p-mTOR/p-S6K activation in neurons by testing with an mTOR inhibitor, rapamycin. Thereafter, we investigated the effects of L-leucine on the spinal cord injury in vivo. A mouse model of spinal cord hemi-section was established, and L-leucine was administered by tail intravenous injection. Basso mouse scale values revealed that L-leucine could improve functional recovery after injury. It was also notable that L-leucine treatment promoted axon growth across chondroitin sulfate proteoglycan (CSPG) areas. Furthermore, we used CSPGs as inhibitory environmental cues and clarified that L-leucine significantly enhanced axonal outgrowth and regeneration by promoting p-mTOR and p-S6K activation. Therefore, our study is the first to report that L-leucine promotes axonal regeneration in vitro and in vivo and could be candidate drug for axonal re-growth and nervous functional recovery.

Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage.

The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.

GIP-GIPR promotes neurite outgrowth of cortical neurons in Akt dependent manner.

The intrinsic capacity of axonal growth is varied among the neurons form different tissues or different developmental stages. In this study, we established an in vitro model to compare the axonal growth of neurons from embryonic 18 days, post-natal 1 day and post-natal 3 days rat. The E18 neurons showed powerful ability of neuritogenensis and axon outgrowth and the ability decreased rapidly along with development. The transcriptome profile of these neurons revealed a set of genes positively correlated with the capacity of neurite outgrowth. Glucose-dependent insulinotropic polypeptide receptor (GIPR) is identified as a gene to promote neurite outgrowth, which was approved by siRNA knock down assay in E18 neuron. Glucose-dependent insulinotropic polypeptide (GIP), a ligand of GIPR secreted from enteroendocrine K cells, is well-known for its role in nutrient sensing and intake. To verify the effect of GIP-GIPR signal on neurite outgrowth, we administrated GIP to stimulate the E18 neurons, the results showed that GIP significantly improved extension of axon. We further revealed that GIP increased Rac1/Cdc42 phosphorylation in Akt dependent manner. In summary, our study established an in vitro model to screen the genes involved in neurite outgrowth, and we provided mechanical insight on the GIP-GIPR axis to promote axonal outgrowth.

[Hematological Analysis and Diagnosis of Two Rare Abnormal Hemoglobin].

OBJECTIVE: To analyze the hematological characteristics of Hb Broomhill and Hb Hornchurch, and prenatal diagnosis should be carried out in two families. METHODS: RBC parameters and hemoglobin electrophoretogram were analyzed on the peripheral blood of all patients, and amniotic fluid was collected for prenatal diagnosis. PCR-Flow fluorescent hybridization and Sanger sequencing were performed for gene diagnosis of thalassemia. RESULTS: Three cases of Hb Broomhill were detected, including 2 cases with common SEA α-thalassemia, which was characterized by hypochromic microcytic mild anemia, the capillary electrophoregram revealed a tiny shoulder peak before the Hb A peak; 1 case was diagnosed as Hb Hornchurch combined with ß-thalassemia, which also showed mild anemia. Hemoglobin electrophoretogram showed an abnormal hemoglobin variant peak at Hb A2 zone. CONCLUSION: The carriers of Hb Broomhill and Hb Hornchurch do not have microcytic hypochromic anemia, which do not aggravate the hematological symptoms, such as anemia when being combined with thalassemia of the same type.

Protective Effect of Compound Formula Rehmannia against Neurotoxicity and Apoptosis Induced by α-Syn in In Vivo and In Vitro Models of Parkinson's Disease.

The present study aimed to investigate the protective effect of compound formula Rehmannia (CFR) against the development of Parkinson's disease (PD). After the in vivo and in vitro models of PD were established with overexpression α-syn induced, CFR was administrated into the PD model rats for 6 weeks or SK-N-SH cells with coincubation for 48 h. Apomorphine-induced rotation test, CCK8 assay, TUNEL assay, immunofluorescence staining, and western blot assay were performed to evaluate the behavioral changes, cell viability, cell apoptosis, α-syn, GSK-3ß, P-GSK-3ß (Ser9), P-GSK-3ß (Tyr216), and ß-catenin expression in PD rats or SK-N-SH cells. PD rat behavior results showed that the rotation numbers were significantly decreased in the CFR treatment group comparing with the AAV-α-syn PD model group. The cell viability suppressed by H2O2 and α-syn in SK-N-SH model cells was also significantly improved with CFR administration. Cell apoptosis and α-syn overexpression observed in PD rats and SK-N-SH cells were also inhibited by CFR treatment. Furthermore, the protein expression of α-syn, GSK-3ß, P-GSK-3ß (Ser9), P-GSK-3ß (Tyr216), and ß-catenin in in vivo and in vitro was also significantly regulated by CFR. The present study suggested that CFR may be considered as a potential neuroprotective agent against PD, and this application will require further investigation.

[Gene Diagnosis and Phenotypic Analysis of ß-Thalassemia Caused from a Rare Synonymous Mutation CD29 (C>T)].

OBJECTIVE: To investigate the gene diagnosis and phenotypes analysis for a couple with ß-thalassemia suspected from of blood routine test and hemoglobin electrophoresis, as well as the prenatal gene diagnosis of the fetus. METHODS: The gene mutation of ß-globin in the samples of peripheral blood of pregnant woman and her husband, as well as amniotic fluid of pregnant woman were analyzied and identified by using PCR-RDB and Sanger sequencing. RESULTS: The detection showed that the heterozygote mutation of IVS-Ⅱ-654 (C>T), which is common mutation of ß-globin gene, existed in pregnant woman, while her husband carried a rare mutation CD29 (c.90 C>T) of ß-globin gene. The prenatal diagnosis indicated that the fetus inherited with mutation from the parents, fetus genotype was ßIVS-Ⅱ-6541/ßCD29. CONCLUSION: The CD29(C>T) mutation of ß-globin gene has been identified in Chinese population first. Although this mutation type is symonymous mutation, but its carrier displays phenotype of ß-thalaessmia. Therefore, the attention to this mutation should be paid considering the genetic risk. It contributes to genetic counseling and prenatal gene diagnosis.

Interactive Echocardiography Translation Using Few-Shot GAN Transfer Learning.

BACKGROUND: Interactive echocardiography translation is an efficient educational function to master cardiac anatomy. It strengthens the student's understanding by pixel-level translation between echocardiography and theoretically sketch images. Previous research studies split it into two aspects of image segmentation and synthesis. This split makes it hard to achieve pixel-level corresponding translation. Besides, it is also challenging to leverage deep-learning-based methods in each phase where a handful of annotations are available. METHODS: To address interactive translation with limited annotations, we present a two-step transfer learning approach. Firstly, we train two independent parent networks, the ultrasound to sketch (U2S) parent network and the sketch to ultrasound (S2U) parent network. U2S translation is similar to a segmentation task with sector boundary inference. Therefore, the U2S parent network is trained with the U-Net network on the public segmentation dataset of VOC2012. S2U aims at recovering ultrasound texture. So, the S2U parent network is decoder networks that generate ultrasound data from random input. After pretraining the parent networks, an encoder network is attached to the S2U parent network to translate ultrasound images into sketch images. We jointly transfer learning U2S and S2U within the CGAN framework. Results and conclusion. Quantitative and qualitative contrast from 1-shot, 5-shot, and 10-shot transfer learning show the effectiveness of the proposed algorithm. The interactive translation is achieved with few-shot transfer learning. Thus, the development of new applications from scratch is accelerated. Our few-shot transfer learning has great potential in the biomedical computer-aided image translation field, where annotation data are extremely precious.

Comparison of neural stem/progenitor cells from adult Gecko japonicus and mouse spinal cords.

The properties and number of neural stem cells (NSCs) in neural tissue are important issues for the regenerative capacity of the spinal cord in different organisms or developmental stages. In this study, we investigated the self-renewal and differentiation potential of NSCs from adult spinal cords of adult geckos (Gecko japonicus) and mice. The sphere forming ratio of mouse NSCs was higher than that of gecko NSCs, and the sphere forming time of mouse NSCs was shorter as well. In addition, serum-induced differentiation of NSCs gave rise to more ß-tubulin III (TUBB3)-positive progeny in geckos, whereas NSCs gave rise to more glial fibrillary acidic protein (GFAP)-positive cells in mice. We further conducted single sphere RNA-seq for both gecko and mouse NSCs, and transcriptome data revealed that purified NSC populations form either geckos or mice are heterogeneous and stay at various differentiated stages even with similar appearance. Mouse NSCs expressed more glial markers and gecko NSCs expressed more neuronal markers, which is consistent with cell fate determination of mouse and gecko NSCs in differentiation assays.

Effects of shikonin from Zicao on high-fat diet-induced nonalcoholic fatty liver disease in rats.

In this study, we aim to investigate whether shikonin prevents against NAFLD. After feeding high-fat diet (HFD) for 10 weeks, Sprague-Dawley rats were received different doses of shikonin (5mg/kg/day, 10mg/kg/day and 20mg/kg/day) by gavage for the last 12 weeks of a total of 22 weeks of a HFD. Our results showed that total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase were significantly increased, while high-density lipoprotein cholesterol was decrease, accompanied by hepatic injury and lipid accumulation in HFD-fed rats. Shikonin treatment attenuated the above biochemical and histopathological changes. Similarly, HFD-induced the increase of hepatic TC and TG levels were also ameliorated by shikonin treatment. Furthermore, shikonin observably mitigated HFD-induced the liver fibrosis and the increase of plasminogen activator inhibitor type 1, connective tissue growth factor, collagen III and IV expression. Additionally, shikonin markedly inhibited HFD-induced the decrease of proliferator-activated receptor γ (PPARγ) and matrix metalloproteinases-9 (MMP-9) expression and the increase of tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in liver tissue. This study demonstrates that shikonin ameliorates hepatic lipid dysregulation and fibrosis through PPARγ and MMP-9/TIMP-1 axis, suggesting that shikonin may be a potential therapeutic agent for the treatment of NAFLD.