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Drug-induced liver injury (DILI) by acetaminophen (APAP) was one of the most challenging liver diseases. Wolfberry (Lycium barbarum L.), a traditional Chinese medicinal material and food supplement, has a potential effect on increasing the abundance of Akkermansia muciniphila (A. muciniphila) in mice colons. However, the effect and mechanism of wolfberry remain unclear in APAP-induced DILI. In this study, wolfberry promoted the proliferation of activated-A. muciniphila in vitro and in vivo. For the first time, we detected that the activated-A. muciniphila but not the killed-A. muciniphila increased the expression level of Yes-associated protein 1 (YAP1) in the liver and alleviated liver injury in APAP-induced DILI mice. Mechanically, A. muciniphila improved the intestinal mucosal barrier and reduced lipopolysaccharide (LPS) content in the liver, leading to the increased expression level of YAP1. Furthermore, wolfberry increased the A. muciniphila abundance in the colon and YAP1 expression in the liver from APAP-induced DILI mice, which promoted the recovery of APAP-induced liver injury. Meanwhile, wolfberry combination with A. muciniphila synergistically increased AKK abundance and YAP1 expression in the liver. Our research provides an innovative strategy to improve DILI.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD.To elucidate the mechanism of SNS in reducing LD deposition in MAFLD.First, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (HE). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction.Cellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the ND group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the NS group in Yap1SNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.

BACKGROUND Hyperpolarized 129 Xe magnetic resonance imaging (MRI) provides a non-invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown. PURPOSE To characterize changes in 129 Xe gas transfer function following administration of an inhaled long-acting beta-agonist/long-acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator. STUDY TYPE Prospective. POPULATION Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy. FIELD STRENGTH/SEQUENCES Dedicated ventilation imaging used a multi-slice 2D gradient echo sequence. Three-dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1-point Dixon sequence. Imaging was acquired at 3 T. ASSESSMENT 129 Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low ) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref ). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO ), were also performed before and after treatment. STATISTICAL TESTS Paired t-test, Pearson correlation coefficient (r). RESULTS Baseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P

Background: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. Methods: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. Results: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. Conclusion: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid.

Growth performance and meat quality are important traits for pig production. The aim of the present study was to investigate the molecular mechanisms underlying growth performance and meat quality, and to identify novel target molecules for predicting the growth performance and meat quality. The differentially expressed genes (DEGs) in Diannan small ears pigs (DSP) and Landrace pigs (LP) were assessed by RNA-sequencing analyzing technology. A total of 339 DEGs were obtained between DSP and LP. 146 DEGs were upregulated in LP compared with DSP and 193 DEGs were upregulated in DSP compared with LP. The DEGs were significantly enriched in 26 GO and 3 KEGG pathways. The protein-protein interaction (PPI) network with 201 nodes and 382 edges was constructed and 5 modules were extracted from the entire network. The identified upregulated expression of genes involved in glycolysis and myogenesis as well as extracellular matrix may be associated with fast body and muscle deposition rates in LP. Increased expression of genes involved in PPAR signaling pathway and fatty acid metabolism as well as oxidative phosphate processes could be related to the intramuscular fat deposition and meat quality in DSP. The present study may provide an improved understanding of the growth performance and meat quality.

BACKGROUND Despite the association of masticatory function with head posture and mandible movement, the impact of head posture on masseter muscle electrical activity remains unclear. This study aimed to investigate the electrical activity of the anterior temporal, masseter, superior trapezius, and sternocleidomastoid muscles in temporomandibular disorder (TMD) patients in three different head positions and compare the findings with those for healthy subjects. METHODS The study included 16 TMD patients and 17 healthy subjects. Surface electromyography (sEMG) was used to assess the bilateral anterior temporalis, masseter, superior trapezius, and sternocleidomastoid muscle activities. The maximal voluntary contraction (MVC) and root mean square (RMS) sequence of each muscle were measured in three head positions. Mixed analysis of variance was used to evaluate the effects of head posture on muscle electrical activity in each group. RESULTS The group differences for the bilateral masseter muscles were significant in the relaxation position, neutral head position (NHP), and relaxation position with tooth contact (P

Objectives Developmental dysplasia of the hip (DDH) is a common skeletal disorder. This study was conducted to demonstrate the association between DDH and a polymorphism rs9277935 of COL11A2 gene. Results A significant difference in genotype distribution in a recessive model (TT+GT vs. GG) between two groups (P=0.017) was demonstrated. Analysis in female patients showed significantly greater frequency of minor allele G(0.49 vs. 0.43, p=0.024) and significantly higher distribution of GG genotype (p=0.006). DDH patients were found to have significantly lower COL11A2 expression than controls. Moreover, DDH patients with rs9277935 genotype TT have a significantly increased expression of COL11A2 than those with genotype GG. COL11A2 demonstrated chondrogenic properties in vitro. Conclusion Polymorphism rs9277935 of gene COL11A2 is a functional variant regulating the expression and the chondrogenic properties of COL11A2 in DDH in Chinese Han population. Methods A case-control candidate gene association study was conducted in 945 patients (350 radiologically confirmed DDH patients and 595 healthy controls). Difference of COL11A2 expression in hip joint tissue was compared between the patients and the controls. Allelic difference in Col11a2 expression by rs9277935 was assessed with luciferase activity. Chondrogenic effects of Col11a2 signaling on BMSCs were also determined in vitro.

BACKGROUND There is no consensus on the association between body posture and temporomandibular disorders (TMDs). This study aimed to assess differences in static balance between healthy participants and patients with temporomandibular joint disc displacement without reduction. MATERIAL AND METHODS Sixteen patients with temporomandibular joint disc displacement without reduction and 14 healthy participants were included. Static balance tests were performed in the rest and "cotton rolls" (participants biting 2 cotton rolls with their upper and lower teeth) mandibular positions. The mean body's center of gravity (COG) sway velocity was tested in each mandibular position on a firm surface with and without eyes open and on a foam surface with and without eyes open. RESULTS The COG sway velocity did not differ between the TMD and healthy groups regarding mandibular position or testing condition (P0.05). However, in the control group, the COG sway velocity in the mandibular rest position was significantly higher than that in the "cotton rolls" mandibular position when standing on a foam surface with the eyes closed (P=0.024). In the TMD group, there was no difference in the COG sway velocity between the 2 mandible positions under any condition (P0.05). CONCLUSIONS This study provides new evidence for static balance alterations in patients with temporomandibular joint disc displacement without reduction. Further studies are needed to investigate postural control changes in patients with arthrogenous TMDs. This study was registered in the Chinese Clinical Trial Registry (no. ChiCTR1800018369).

PURPOSE: To reduce scan duration in hyperpolarized (129)Xe 1-point Dixon gas exchange imaging by utilizing flip angle (FA)/TR equivalence. METHODS: Images were acquired in 12 subjects (N = 3 radiation therapy, N = 1 unexplained dyspnea, N = 8 Healthy) using both standard (TR = 15 ms, FA = 20°, Duration = 15 s, 998 projections) and “fast” (TR = 5.4 ms, FA = 12°, Duration = 11.3 s, 2100 projections) acquisition parameters. For the “fast” acquisition, three image sets were reconstructed using subsets of 1900, 1500, and 1000 projections. From the resulting ventilation, tissue (“barrier”), and red blood cell (RBC) images, image metrics and biomarkers were compared to assess agreement between methods. RESULTS: Images acquired using both FA/TR settings had similar qualitative appearance. There were no significant differences in SNR, image mean, or image standard deviation between images. Moreover, the percentage of the lungs in “defect”, “normal”, and “high” bins for each image (ventilation, RBC, Barrier) was not significantly different among the acquisition types. After registration, comparison of 3D image metrics (Dice, volume similarity, average distance) agreed well between bins. Images using 1000 projections for reconstruction had no significant differences from images using all projections. CONCLUSION: Using flip angle/TR equivalence, hyperpolarized (129)Xe gas exchange images can be acquired via the 1-point Dixon technique in as little as 6 s, compared to ~15 s for previously reported parameter settings. The resulting images from this accelerated scan have no significant differences from the standard method in qualitative appearance or quantitative metrics.

Spectral cytopathology (SCP) is a promising label-free technique for diagnosing diseases and monitoring therapeutic outcomes using FTIR spectroscopy. In most cases, cells must be immobilized on a substrate prior to spectroscopic interrogation. This creates significant limitations for high throughput phenotypic whole-cell analysis, especially for the non-adherent cells. Here we demonstrate how metasurface-enhanced infrared reflection spectroscopy (MEIRS) can be applied to a continuous flow of live cell solution by applying AC voltage to metallic metasurfaces. By integrating metasurfaces with microfluidic delivery channels and attracting the cells to the metasurface via dielectrophoretic (DEP) force, we collect the infrared spectra of cells in real time within a minute, and correlate the spectra with simultaneously acquired images of the attracted cells. The resulting DEP-MEIRS technique paves the way for rapid SCP of complex cell-containing body fluids with low cell concentrations, and for the development of a wide range of label-free liquid biopsies.

BACKGROUND. Hyperpolarized (129)Xe MRI provides a non-invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown. PURPOSE. To characterize changes in (129)Xe gas transfer function following administration of an inhaled long-acting beta-agonist/long-acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator. STUDY TYPE. Prospective. POPULATION. 17 COPD subjects (GOLD ll/lll classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy. FIELD STRENGTH/SEQUENCES. Dedicated ventilation imaging used a multi-slice 2D gradient echo sequence. 3D images of ventilation, barrier uptake and RBC transfer used an interleaved, radial, 1-point Dixon sequence. Imaging was acquired at 3T. ASSESSMENT. (129)Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect+low percent (ven(def+low)) and by barrier uptake and RBC transfer relative to a healthy reference population (bar(%ref) and RBC(%ref)). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DL(co)), were also performed before and after treatment. STATISTICAL TESTS: Paired t-test, Pearson correlation coefficient (r). RESULTS. Baseline ven(def+low) was 57.8±8.4%, bar(%ref) was 73.2%±19.6%, and RBC(%ref) was 36.5%±13.6%. Following treatment, ven(def+low) decreased to 52.5±10.6% (p

Hyperpolarized (129)Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of (129)Xe gas-exchange MRI to estimate accessible alveolar volume (V(A)), membrane conductance, and capillary blood volume contributions to DL(CO). (129)Xe ventilated volume (VV) was related to V(A) by a scaling factor k(V) = 1.47 with 95% confidence interval [1.42, 1.52], relative (129)Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient k(B) = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient k(R) = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient K(CO), which was then multiplied by image-estimated V(A) to obtain DL(CO). The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting (129)Xe-derived DL(CO) correlated strongly (R(2) = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use (129)Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DL(CO) clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally. NEW & NOTEWORTHY The diffusing capacity for carbon monoxide (DL(CO)) is perhaps one of the most comprehensive physiological measures used in pulmonary medicine. Here, we spatially resolve and estimate its key components—accessible alveolar volume, membrane, and capillary blood volume conductances—using hyperpolarized (129)Xe MRI of ventilation, interstitial barrier uptake, and red blood cell transfer. This image-derived DL(CO) correlates strongly with measured values in 142 subjects with a broad range of pulmonary disorders.

Through lyrics, pitch, and rhythm, music is a natural way of expressing one’s thoughts. As one of the essential music composition elements, lyrics composition is complicated as it requires creativity and follows a particular rhythm pattern. This thesis created two neural network models for composing lyrics in three genres and produced scoring functions to select and evaluate generated songs. We treat this problem as a text generation task. We analyzed the features of lyrics in different genres. The neural networks we have experimented with are generative adversarial network (GAN) based transfer learning for a deep learning model and recurrent neural network (RNN) and long short-term memory (LSTM) based deep learning model. The lyrics evaluation functions consider lyrics’ quality, rhyme density, and sentiment ratio. As a part of the quantitative evaluation, we also conducted user studies, and we invited 25 people to rate the generative songs selected by the scoring functions. We discovered that the GAN based models perform better than RNN-LSTM based models and the scoring functions are useful in choosing good songs.

The lower limbs exoskeleton rehabilitation robot (LLERR) has been used widely in rehabilitation training of human lower limb injury, where the control research of LLERR is still a hot point in robotics. Therefore, in this paper, a trajectory tracking adaptive control based on human gait is proposed. Where, the real gait trajectory of human body mechanism by using NOKOV motion capture system is used in control system design. In the simulation results, the dynamics model uncertainty are also considered, and the real gait trajectory data of human body is used to the control system. According to the simulation results, when there is uncertainty in the LLERR model, the proposed trajectory tracking adaptive control method can improve the accuracy and reliability of the trajectory tracking, which makes it suitable for different patients. By adaptive control, the uncertain part of the LLERR is compensated, and the structure parameters of the robot are obtained.

For a long time researchers have focused on the binary classification of domain names sent to DNS servers for resolutions to IP addresses. The objective is to identify malicious domains versus legitimate ones to protect networks from attacks. For legitimate domains, an emerging interest is to classify them into content categories to enable DNS servers deployed in an organization to monitor and potentially block the resolution of irrelevant domains. For example, a financial organization wants to flag gaming related domains, and an elementary school wants to block suspicious adult domains. Classifying a domain by just the domain name is a challenging task. Currently, there exist no publicly available datasets that include an extensive mapping of domains to content categories, since this is usually proprietary information. Our focus is three-fold in this work: a) to develop a data collection methodology and create rich labelled datasets that are appropriate for training such predictive models, b) to share the datasets with the research community by making them publicly available, and c) to evaluate and identify appropriate machine learning and deep learning algorithms for this problem domain. We consider two different datasets. The first is created following a SERP (Search Engine Response Page)-mining approach, having a set of content categories as input. The second is an enhancement of the DMOZ dataset that is publicly available, including both domains and category names as input. In addition to the dataset creation input and methodology, these two datasets differ in the content category number and distribution, yielding different results in our analysis. Overall, we observe that the deep learning-based approach carefully considers the key features of the input data and hence outperforms existing traditional machine learning pipelines, achieving 98.37% and 79.29% accuracy on the respective datasets.

Background Sleep bruxism (SB) patients show a higher incidence of leg movements than normal subjects. Study objectives The study aimed to characterize SB episodes and their relationships with limb movements (LMs). Materials and methods Polysomnographic (PSG) recordings were performed on eight SB patients. The intervals between the onsets of adjacent SB episodes and LMs were determined and linear correlation analyses were used to estimate the relationship between the SB index and SB episodes in clusters. The Pearson χ2 and partitions of χ2 tests were used to analyze the differences in incidence of SB episodes and clusters in different sleep stages. Results A majority of SB episodes (85.05%) were found to be accompanied by LMs and among them, 70.52% SB episodes occurred with movements of both upper and lower limbs and most of LMs (70.54%) occurred before the onset of SB episodes. Most of SB episodes especially those accompanied by LMs occurred with microarousals or awakenings. Linear correlation analysis showed a positive correlation between the SB index and SB episodes in clusters (r2 = 0.7027, P = 0.0093). In addition, the percentage of SB episodes in clusters accompanied by LMs was significantly smaller than that of SB episodes not accompanied by LMs (χ2 test, P Conclusions Most SB episodes might not be isolated events, but rather a part of a series of movements second to changes in arousal level.

Objectives: Developmental dysplasia of the hip (DDH) is a common skeletal disorder. This study was conducted to demonstrate the association between DDH and a polymorphism rs9277935 of COL11A2 gene. Results: A significant difference in genotype distribution in a recessive model (TT+GT vs. GG) between two groups (P=0.017) was demonstrated. Analysis in female patients showed significantly greater frequency of minor allele G(0.49 vs. 0.43, p=0.024) and significantly higher distribution of GG genotype (p=0.006). DDH patients were found to have significantly lower COL11A2 expression than controls. Moreover, DDH patients with rs9277935 genotype TT have a significantly increased expression of COL11A2 than those with genotype GG. COL11A2 demonstrated chondrogenic properties in vitro. Conclusion: Polymorphism rs9277935 of gene COL11A2 is a functional variant regulating the expression and the chondrogenic properties of COL11A2 in DDH in Chinese Han population. Methods: A case-control candidate gene association study was conducted in 945 patients (350 radiologically confirmed DDH patients and 595 healthy controls). Difference of COL11A2 expression in hip joint tissue was compared between the patients and the controls. Allelic difference in Col11a2 expression by rs9277935 was assessed with luciferase activity. Chondrogenic effects of Col11a2 signaling on BMSCs were also determined in vitro.

DNS request classification is an area that has received a lot of attention, mostly as part of network security process, in order to classify requests into malicious and non-malicious. However, there exist several categories of web pages that even though not malicious, they belong to “borderline” categories and need to be monitored. For instance, websites selling illegal substances or weapons might be of interest for any public or private organization to monitor as outgoing traffic. In this work, we treat this as a topic classification problem. We present and evaluate a machine learning framework that takes as input a domain name (based on the respective DNS request) and outputs the content category it belongs to. We evaluate several options for feature engineering and classification to find the most appropriate setup for the specific problem domain. We also address the problem of data collection and preprocessing. While there exist several labelled datasets with malicious/non-malicious requests, a similar labelled dataset does not exist for general web content categories. We therefore propose a SERP (Search Engine Response Pages)-mining approach to collect and label an appropriate dataset. Our experimental evaluation uncovers several interesting insights and forms the basis for further work into this interesting domain.

Patients with chronic ankle instability (CAI) have postural-control deficits during center-of-pressure excursions than do healthy individuals. While an external analysis of center-of-pressure excursions in CAI has been performed, a quantitative analysis of center-of-gravity movements, to detect the balance deficits associated with CAI, has yet to be performed. Therefore, the aim of the study is to quantify the balance deficits in patients with unilateral CAI. Forty-four patients with unilateral CAI (24 men; age, 31.7 ± 5.5 years) and 26 uninjured volunteers (12 men; age, 28.6 ± 5.9 years) underwent Neurocom Balance Manager assessments of dynamic and static balance responses in limits of stability, unilateral stance, and forward lunge tests. In the limits of stability test, there were no significant group differences in the forward direction; however, reaction times were longer in the CAI group than in the control group in the backward (P = .037, effect size [ES] = 0.49) and rightward directions (P = .032, ES = 0.47). Furthermore, the CAI group showed more excursions in the rightward (P = .046, ES = 0.50) and leftward directions (P = .002, ES = 0.80), and less directional control in the leftward direction (P = .036, ES = 0.59). In the unilateral stance test, the center of gravity sway velocity was faster in the CAI group than in the control group, whether eyes were opened or closed (P < .05). There were no significant group differences in forward lunge-test outcomes. Patients with CAI have poor static and dynamic balance performance compared to that in healthy counterparts. Thus, balance retraining should be an essential component of rehabilitation programs for patients with CAI.