Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI.

BACKGROUND AND PURPOSE: Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD. MATERIALS AND METHODS: The study enrolled 28 patients with WD (19 with neurologic symptoms) and 25 controls. Fractional anisotropy (FA), mean diffusivity (MD), and magnetic susceptibility in globus pallidus, pontine tegmentum, dentate nucleus, red nucleus, head of caudate nucleus, putamen, substantia nigra, and thalamus were extracted. Correlations between imaging data and the Unified Wilson's Disease Rating Scale (UWDRS) neurologic subitems were explored. RESULTS: FA, MD, and susceptibility values were higher in multiple DGN of patients with WD than controls (P < .05). Patients with WD without abnormal signals in DGN on routine MRI also had higher FA, MD, and susceptibility values than controls (P < .017). We found that UWDRS neurologic subscores correlated with FA and susceptibility values of DGN (P < .05). In addition, we also found that FA and susceptibility values in specific structures correlated with specific neurologic symptoms of WD (ie, tremor, parkinsonism, dysarthria, dystonia, and ataxia) (P < .05). CONCLUSIONS: Patients with WD have increased FA, MD, and susceptibility values even before the lesion is morphologically apparent on routine MRI. The increased FA and susceptibility values correlate with clinical severity of WD.

Evaluation of carcass traits, meat quality and the expression of lipid metabolism-related genes in different slaughter ages and muscles of Taihang black goats.

OBJECTIVE: This study was conducted to investigate the effect of slaughter age on carcass traits, meat quality, and the relative mRNA levels of lipid metabolism-related genes in different muscles of Taihang black goats. METHODS: In this study, the triceps brachii (TB), longissimus dorsi (LD) and gluteus (GL) muscles of 15 grazing Taihang black goats slaughtered at the age of 2, 3, and 4 (designated as 2-year-old, 3-year-old, and 4-year-old, respectively) were collected. The differences in carcass shape, meat quality, amino acid composition and lipid metabolism gene expression among Taihang black goats of different ages and from different plant parts were compared. RESULTS: Compared with goats at other ages, goats slaughtered at the age of 4 had greater live and carcass weights, meat weights, bone weights and skin areas (p<0.05). LD in the 4-years-old had the lowest cooking loss and moisture content. The crude protein content in the LD of 2-year-old was significantly greater than that in the other age group, and at the age of 2, the LD had the highest crude protein content than TB and GL. The highest fat content was in LD, followed by TB, for goats slaughtered at the age of 4. Eight out of 9 essential amino acids had higher content in the TB compared with other muscles, regardless of age. The total essential amino acid content was highest in the 4-year-old and lowest in the GL muscle at the age of 3. The sterol regulatory element-binding protein-1c (SREBP-1c) and adipose triglyceride lipase (ATGL) genes were significantly more abundant in the TB muscle than in the other muscles for goats slaughtered at the age of 2. At the age of 4, the ATGL and peroxisome proliferator-activated receptor γ (PPARγ) genes were significantly more abundant in the GL than in the LD, while the fatty acid synthase (FAS) genes were significantly less abundant in the GL than in the other muscles. Similarly, compared with those in goats of other ages, the relative mRNA expression levels of the FAS and heart-type fatty acid binding protein (H-FABP) genes in goats slaughtered at the age of 4 were the highest, and the relative mRNA expression of the PPARγ gene was the lowest (p<0.05). The relative mRNA expression of the H-FABP and FAS genes was positively correlated with the intramuscular fat (IMF) content, while the relative mRNA expression levels of the PPARγ and ATGL genes was negatively correlated with the IMF content. CONCLUSION: Overall, a better nutritional value was obtained for TB from 4-year-old goats, in which the total essential amino acid and fat contents were greater than those of other muscles. The comprehensive action of lipid metabolism genes was consistent with that of the IMF content, among which the FAS, H-FABP, PPARγ, and ATGL genes had positive and negative effects on the process of IMF deposition in Taihang black goats.

Magnetic susceptibility and R2*-based texture analysis for evaluating liver fibrosis in chronic liver disease.

PURPOSE: To explore potential feasibility of texture features in magnetic susceptibility and R2* maps for evaluating liver fibrosis. METHODS: Thirty-one patients (median age 46 years; 22 male) with chronic liver disease were prospectively recruited and underwent magnetic resonance imaging (MRI), blood tests, and liver biopsy. Susceptibility and R2* maps were obtained using a 3-dimensional volumetric interpolated breath-hold examination sequence with a 3T MRI scanner. Texture features, including histogram, gray-level co-occurrence matrix (GLCM), gray-level dependence matrix (GLDM), gray-level run length matrix (GLRLM), gray-level size zone matrix (GLSZM), and neighboring gray tone difference matrix (NGTDM) features, were extracted. Texture features and blood test results of non-significant (Ishak-F < 3) and significant fibrosis patients (Ishak-F ≥ 3) were compared, and correlations with Ishak-F stages were analyzed. Areas under the curve (AUCs) were calculated to determine the efficacy for evaluating liver fibrosis. RESULTS: Nine texture features of susceptibility maps and 19 features of R2* maps were significantly different between non-significant and significant fibrosis groups (all P < 0.05). Large dependence high gray-level emphasis (LDHGLE) of GLDM and long run high gray-level emphasis (LRHGLE) of GLRLM in R2* maps showed significantly negative and good correlations with Ishak-F stages (r = -0.616, P < 0.001; r = -0.637, P < 0.001). Busyness (NGTDM) in susceptibility maps, LDHGLE of GLDM and LRHGLE of GLRLM in R2* maps yield the highest AUCs (AUC = 0.786, P = 0.007; AUC = 0.807, P = 0.004; AUC = 0.819, P = 0.003). CONCLUSION: Texture characteristics of susceptibility and R2* maps revealed possible staging values for liver fibrosis. Susceptibility and R2*-based texture analysis may be a useful and noninvasive method for staging liver fibrosis.

Potential selection for lipid kinase activity and spermatogenesis in Henan native pig breeds and growth shaping by introgression of European genes.

BACKGROUND: China has one third of the worldwide indigenous pig breeds. The Henan province is one of the earliest pig domestication centers of China (about 8000 years ago). However, the precise genetic characteristics of the Henan local pig breeds are still obscure. To understand the origin and the effects of selection on these breeds, we performed various analyses on lineage composition, genetic structure, and detection of selection sweeps and introgression in three of these breeds (Queshan, Nanyang and Huainan) using genotyping data on 125 Queshan, 75 Nanyang, 16 Huainan pigs and 878 individuals from 43 Eurasian pig breeds. RESULTS: We found no clear evidence of ancestral domestic pig DNA lineage in the Henan local breeds, which have an extremely complicated genetic background. Not only do they share genes with some northern Chinese pig breeds, such as Erhualian, Hetaodaer, and Laiwu, but they also have a high admixture of genes from foreign pig breeds (33-40%). Two striking selection sweeps in small regions of chromosomes 2 and 14 common to the Queshan and Nanyang breeds were identified. The most significant enrichment was for lipid kinase activity (GO:0043550) with the genes FII, AMBRA1, and PIK3IP1. Another interesting 636.35-kb region on chromosome 14 contained a cluster of spermatogenesis genes (OSBP2, GAL3ST1, PLA2G3, LIMK2, and PATZ1), a bisexual sterility gene MORC2, and a fat deposition gene SELENOM. Reproduction and growth genes LRP4, FII, and ARHGAP1 were present in a 238.05-kb region on SSC2 under selection. We also identified five loci associated with body length (P = 0.004) on chromosomes 1 and 12 that were introgressed from foreign pig breeds into the Henan breeds. In addition, the Chinese indigenous pig breeds fell into four main types instead of the previously reported six, among which the Eastern type could be divided into two subgroups. CONCLUSIONS: Admixture of North China, East China and foreign pigs contributed to high genetic diversity of Henan local pigs. Ontology terms associated with lipid kinase activity and spermatogenesis and growth shaping by introgression of European genes in Henan pigs were identified through selective sweep analyses.

Hydrophobically modified hydrogel with enhanced tissue adhesion and antibacterial capacity for wound healing.

The increasing emergence of drug-resistant bacteria and bacteria-infected wounds highlights the urgent need for new kinds of antibacterial wound dressing. Herein, we reported a novel bio-adhesive and antibacterial hydrogel consisting of hydrophobically modified gelatin, oxidized konjac glucomannan, and dopamine. This kind of functional hydrogel was endowed with developed stability in a liquid environment and strong tissue adhesion, even much higher than the commercial fibrin glue to wounds. The excellent bacteria-killing efficiency of hydrophobically modified hydrogel against S. aureus and E. coli was verified, as well as the low hemolysis ratio against erythrocytes in vitro. The hydrogel also exhibited good cytocompatibility in terms of supporting cell proliferation. Most importantly, these abovementioned properties could be customized by altering the substitution degree of hydrophobic groups during manufacturing, demonstrating its great potential in biomedical fields such as tissue adhesive and wound dressing.

Age-dependent changes in brain iron deposition and volume in deep gray matter nuclei using quantitative susceptibility mapping.

BACKGROUND: Microstructural changes in deep gray matter (DGM) nuclei are related to physiological behavior, cognition, and memory. Therefore, it is critical to study age-dependent trajectories of biomarkers in DGM nuclei for understanding brain development and aging, as well as predicting cognitive or neurodegenerative diseases. OBJECTIVES: We aimed to (1) characterize age-dependent trajectories of mean susceptibility, adjusted volume, and total iron content simultaneously in DGM nuclei using quantitative susceptibility mapping (QSM); (2) examine potential contributions of sex related effects to the different age-dependence trajectories of volume and iron deposition; and (3) evaluate the ability of brain age prediction by combining mean magnetic susceptibility and volume of DGM nuclei. METHODS: Magnetic susceptibilities and volumetric values of DGM nuclei were obtained from 220 healthy participants (aged 10-70 years) scanned on a 3T MRI system. Regions of interest (ROIs) were drawn manually on the QSM images. Univariate regression analysis between age and each of the MRI measurements in a single ROI was performed. Pearson correlation coefficients were calculated between magnetic susceptibility and adjusted volume in a single ROI. The statistical significance of sex differences in age-dependent trajectories of magnetic susceptibilities and adjusted volumes were determined using one-way ANCOVA. Multiple regression analysis was used to evaluate the ability to estimate brain age using a combination of the mean susceptibilities and adjusted volumes in multiple DGM nuclei. RESULTS: Mean susceptibility and total iron content increased linearly, quadratically, or exponentially with age in all six DGM nuclei. Negative linear correlation was observed between adjusted volume and age in the head of the caudate nucleus (CN; R2 = 0.196, p < 0.001). Quadratic relationships were found between adjusted volume and age in the putamen (PUT; R2 = 0.335, p < 0.001), globus pallidus (GP; R2 = 0.062, p = 0.001), and dentate nucleus (DN; R2 = 0.077, p < 0.001). Males had higher mean magnetic susceptibility than females in the PUT (p = 0.001), red nucleus (RN; p = 0.002), and substantia nigra (SN; p < 0.001). Adjusted volumes of the CN (p < 0.001), PUT (p = 0.030), GP (p = 0.007), SN (p = 0.021), and DN (p < 0.001) were higher in females than those in males throughout the entire age range (10-70 years old). The total iron content of females was higher than that of males in the CN (p < 0.001), but lower than that of males in the PUT (p = 0.014) and RN (p = 0.043) throughout the entire age range (10-70 years old). Multiple regression analyses revealed that the combination of the mean susceptibility value of the PUT, and the volumes of the CN and PUT had the strongest associations with brain age (R2 = 0.586). CONCLUSIONS: QSM can be used to simultaneously investigate age- and sex- dependent changes in magnetic susceptibility and volume of DGM nuclei, thus enabling a comprehensive understanding of the developmental trajectories of iron accumulation and volume in DGM nuclei during brain development and aging.

Relationship Between Iron Distribution in Deep Gray Matter Nuclei Measured by Quantitative Susceptibility Mapping and Motor Outcome After Deep Brain Stimulation in Patients With Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor deficits in advanced Parkinson's disease (PD) patients, but the degree of motor improvement varies across individuals. PD pathology involves the changes of iron spatial distribution in the deep gray matter nuclei. PURPOSE: To explore the relationship between the iron spatial distribution and motor improvement among PD patients who underwent STN-DBS surgery in three regions: substantia nigra (SN), STN, and dentate nucleus (DN). STUDY TYPE: Prospective. SUBJECTS: Forty PD patients (49.7 ± 8.8 years, 22 males/18 females) who underwent bilateral STN-DBS. FIELD STRENGTH/SEQUENCE: A 3 T preoperative three-dimensional spoiled bipolar-readout multi-echo gradient recalled echo and two-dimensional fast spin echo sequences. ASSESSMENT: Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) scores were assessed 2-3 days before and 6 months after STN-DBS. The first- and second-order texture features in regions of interest were measured on susceptibility maps. STATISTICAL TESTS: Intraclass correlation coefficient was used to determine the consistency of the region of interest volumes delineated by the two raters. Pearson or Spearman's correlation coefficients were used to assess the relationship between motor improvement after DBS and texture features. A P-value <0.05 was considered statistically significant. RESULTS: MDS-UPDRS III scores were reduced by 59.9% after STN-DBS in 40 PD patients. Motor improvement correlated with second-order texture parameters in the SN including angular second moment (r = -0.449), correlation (rho = 0.326), sum of squares (r = 0.402), sum of entropy (rho = 0.421), and entropy (r = 0.410). Additionally, DBS outcome negatively correlated with mean susceptibility values in the DN (r = -0.400). DATA CONCLUSION: PD patients with a more homogeneous iron distribution throughout the SN or a higher iron concentration in the DN responded worse to STN-DBS. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Free water imaging as a novel biomarker in Wilson's disease: A cross-sectional study.

BACKGROUND: The bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients. METHODS: The study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FAT) in DGM nuclei of WD patients were calculated. The correlations of free water and FAT with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed. RESULTS: Free water and FAT values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FAT values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FAT values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FAT values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia. CONCLUSIONS: Free water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients.

Increased Magnetic Susceptibility in the Deep Gray Matter Nuclei of Wilson's Disease: Have We Been Ignoring Atrophy?

Background: Histopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls. Methods: Quantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility. Results: Mean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively. Conclusion: Brain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.

Multi-Crosslinked Hydrogels with Instant Self-Healing and Tissue Adhesive Properties for Biomedical Applications.

Due to the defects like long gelling time, inferior mechanical properties and weak adhesion, in situ forming hydrogels are still restricted in biomedical applications like viscera rupture and targeted therapy. To address these problems, a new kind of multi-crosslinked hydrogel (G-OKG-DA) consisting of gelatin, oxidized konjac glucomannan (OKG), and dopamine (DA) is proposed in this study. The resulting hybrid hydrogel is endowed with a short gelling time (≈3 min) and injectable capacity. According to the mechanical and adhesive tests, G-OKG-DA hydrogel shows a robust tensile strength of 23.94 kPa, as well as a higher adhesive strength (≈150 kPa) than commercial fibrin glue. In addition, an instant self-healing behavior of G-OKG-DA hydrogel can be found, which is attributed to multi-cross-linking reactions including Schiff-based dynamic covalent bonds between OKG and gelatin, oxidative polymerization of DA, and catechol-mediated chemistry like Michael addition and DA-quinone coupling. Importantly, the multi-crosslinked hydrogel will not compromise its hemocompatibility and cytocompatibility in vitro, suggesting potential applications in biomedical fields as tissue adhesive and implants.

Automated Segmentation of Midbrain Structures in High-Resolution Susceptibility Maps Based on Convolutional Neural Network and Transfer Learning.

BACKGROUND: Accurate delineation of the midbrain nuclei, the red nucleus (RN), substantia nigra (SN) and subthalamic nucleus (STN), is important in neuroimaging studies of neurodegenerative and other diseases. This study aims to segment midbrain structures in high-resolution susceptibility maps using a method based on a convolutional neural network (CNN). METHODS: The susceptibility maps of 75 subjects were acquired with a voxel size of 0.83 × 0.83 × 0.80 mm3 on a 3T MRI system to distinguish the RN, SN, and STN. A deeply supervised attention U-net was pre-trained with a dataset of 100 subjects containing susceptibility maps with a voxel size of 0.63 × 0.63 × 2.00 mm3 to provide initial weights for the target network. Five-fold cross-validation over the training cohort was used for all the models' training and selection. The same test cohort was used for the final evaluation of all the models. Dice coefficients were used to assess spatial overlap agreement between manual delineations (ground truth) and automated segmentation. Volume and magnetic susceptibility values in the nuclei extracted with automated CNN delineation were compared to those extracted by manual tracing. Consistencies of volume and magnetic susceptibility values by different extraction strategies were assessed by Pearson correlation coefficients and Bland-Altman analyses. RESULTS: The automated CNN segmentation method achieved mean Dice scores of 0.903, 0.864, and 0.777 for the RN, SN, and STN, respectively. There were no significant differences between the achieved Dice scores and the inter-rater Dice scores (p > 0.05 for each nucleus). The overall volume and magnetic susceptibility values of the nuclei extracted by the automatic CNN method were significantly correlated with those by manual delineation (p < 0.01). CONCLUSION: Midbrain structures can be precisely segmented in high-resolution susceptibility maps using a CNN-based method.

Glutamate correlates negatively with cognitive theory of mind in schizotypy.

This study showed a negative correlation between the glutamate level in the anterior cingulate cortex and cognitive theory of mind in individuals with high level of schizotypy but not in non-schizotypy individuals.

Striatal GABA level is associated with sensory integration ability in individuals with low levels of negative schizotypy.

Recent studies suggest that altered gamma-aminobutyric acidergic (GABAergic) function may result in multisensory integration deficits in schizophrenia. However, it is unclear whether the GABA level is abnormal in individuals with high levels of schizotypal traits and how it would correlate with sensory integration ability in these individuals. This study aimed to compare the GABA level between individuals with high and low levels of negative schizotypy, and examine the relationship between GABA levels and sensory integration ability in each group. In vivo GABA+ and N-acetylaspartate (NAA) levels in the striatum were measured using proton magnetic resonance imaging in 19 participants with high levels of negative schizotypy and 21 participants with low levels of negative schizotypy. The Sensory Integration subscale of the abridged version of the Cambridge Neurological Inventory was used. We examined the group differences in GABA+/NAA levels, and the correlation between striatal GABA+/NAA levels and sensory integration ability in each group. The two groups showed comparable levels of in-vivo GABA+/NAA. In-vivo GABA+/NAA levels were negatively correlated with sensory integration score in participants with low levels of negative schizotypy, but not in participants with high levels of negative schizotypy. Our findings indicate that the increased GABA level is correlated with better sensory integration ability in individuals with low levels of negative schizotypy, implicating the role of GABAergic function in multisensory integration. Unlike schizophrenia patients, individuals with high levels of schizotypy do not exhibit any abnormality in their GABAergic system and sensory integration ability.

Effects of dietary supplementation with alpha-lipoic acid on apparent digestibility and serum metabolome alterations of sheep in summer.

To investigate the effects of alpha-lipoic acid (LA) on the nutrition metabolism of sheep (36.72 ± 1.44 kg) in the summer, twenty-one sheep were randomly assigned to three treatments addressing LA supplementation: 0.00 (CTL), 600 (LA-L), and 900 (LA-H) mg/kg of dry matter (DM) per day for each sheep. Whole feces and urine collection methods were used to analyze apparent digestibility; ELISA kits to determine the hormones, antioxidant, and immune parameters in the blood; and serum metabolomics to detect and analyze small molecular substances. The results showed the DM intakes in the LA-L and LA-H groups were significantly increased by 8.22% and 8.02%, respectively, compared to that in the CTL group, and there was no significant effect on average daily gain, feed conversion ratio, nitrogen digestibility, calcium digestibility, and phosphorus digestibility. Regarding hormones, antioxidant, and immune indicators, the concentrations of triiodothyronine, superoxide dismutase, glutathione reductase, HSP70, and IgA significantly increased after LA supplementation, while adrenaline and malondialdehyde levels significantly decreased. With the pairwise comparison of the three groups, metabolomics analysis identified 22 differential metabolites in the positive/negative modes, respectively, which suggested LA supplementation can significantly affect sheep's lipid, amino acid, and nucleic acid metabolism. Additionally, 3-indolepropionic acid, cinnamoylglycine, butyric acid, dodecanedioic acid, indoxyl sulfate, and pantothenic acid were the common differential metabolites with higher concentrations after LA supplementation. In summary, dietary supplementation of LA can increase the sheep's DMI, energy digestibility, antioxidant capacity, and immunity. These changes provide evidence to support the use of LA supplementation for livestock.

Analysis of mRNA and Long Non-Coding RNA Expression Profiles in Developing Yorkshire Pig Spleens.

Epidemic diseases cause great economic loss in pig farms each year; some of these diseases are characterized mainly in the spleen, but mRNA and lncRNA (long non-coding RNA) expression networks in developing Yorkshire pig spleens remain obscure. Here, we profiled the systematic characters of mRNA and lncRNA repertoires in three groups of spleens from nine Yorkshire pigs, each three aged at seven days, 90 days, and 180 days. By using a precise mRNA and lncRNA identification pipeline, we identified 19,647 genes and 219 known and 3219 putative lncRNA transcripts; 1729 genes and 64 lncRNAs therein were found to express differentially. The gene expression characteristics of genes and lncRNAs were found to be basically fixed before 90 days after birth. Three large gene expression modules were detected. The enrichment analyses of differentially expressed genes and the potential target genes of differentially expressed lncRNAs both displayed the crucial roles of up-regulation in immune activation and hematopoiesis, and down-regulation in cell replication and division in 90 days and 180 days compared to seven days. ENSSSCT00000001325 was the only lncRNA transcript that existed in the three groups. CDK1, PCNA, and PLK were detected to be node genes that varied with age. This study contributes to a further understanding of mRNA and lncRNA expression in different developmental pig spleens.

Gelatin/Oxidized Konjac Glucomannan Composite Hydrogels with High Resistance to Large Deformation for Tissue Engineering Applications.

In this study, gelatin hydrogels with remarkable compressive properties and recoverability were prepared via Shiff's base chemical cross-linking between gelatin and oxidized konjac glucomannan (OKG). The process of OKG was first optimized by adjusting parameters, that is, oxidation temperature and time during processing. Various percentages of obtained OKG (1, 2, 3, 4, and 5 wt % to gelatin) were introduced to make composite hydrogels (G-OKGs). These G-OKGs were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, swelling ratio, and mechanical tests. In comparison with pure gelatin hydrogels, the G-OKGs exhibit significantly increased stress and modulus, and favorable recoverability after cyclic large deformation (up to 85% of the original height). Additionally, G-OKGs with uniform porous structures are biocompatible to support the proliferation of human umbilical vein endothelial cells. In conclusion, this study provides a reference for developing mechanically stable and recoverable hydrogels, and these kinds of hydrogels show potential capacity in tissue engineering and biomedical applications that may be undergoing extra forces and large deformation.

Investigation on the tunable effect of oxidized konjac glucomannan with different molecular weight on gelatin-based composite hydrogels.

Herein, oxidized konjac glucomannan (OKG) with different molecular weight (Mw) were prepared as polysaccharide crosslinker to reinforce gelatin-based hydrogels. Then, properties of composite hydrogels with various OKGs were investigated via a series of methods, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), rheology, mechanical and biocompatibility tests. The results confirmed an increased degree of crosslinking and entanglement between gelatin and OKG with higher Mw. Besides, composite hydrogels not only showed increased mechanical strength, but self-healing ability at the same time, which were closely affected by the Mw of OKG. Furthermore, both composite hydrogels could support well proliferation of cells, which showed excellent capacity in tissue engineering and biomedical applications. In brief, this work provides a facile method to promote the overall properties of gelatin-based hydrogels, meanwhile revealed the relationship and mechanism underlying the effects of OKG with different Mw on composite hydrogels.

Paramagnetic Metal Accumulation in the Deep Gray Matter Nuclei Is Associated With Neurodegeneration in Wilson's Disease.

BACKGROUND: Neuropathological studies have revealed copper and iron accumulation in the deep gray matter (DGM) nuclei of patients with Wilson's disease (WD). However, the association between metal accumulation and neurodegeneration in WD has not been well studied in vivo. The study was aimed to investigate whether metal accumulation in the DGM was associated with the structural and functional changes of DGM in neurological WD patients. METHODS: Seventeen neurological WD patients and 20 healthy controls were recruited for the study. Mean bulk susceptibility values and volumes of DGM were obtained from quantitative susceptibility mapping (QSM). Regions of interest including the head of the caudate nucleus, globus pallidus, putamen, thalamus, substantia nigra, red nucleus, and dentate nucleus were manually segmented. The susceptibility values and volumes of DGM in different groups were compared using a linear regression model. Correlations between susceptibility values and volumes of DGM and Unified Wilson's Disease Rating Scale (UWDRS) neurological subscores were investigated. RESULTS: The susceptibility values of all examined DGM in WD patients were higher than those in healthy controls (P < 0.05). Volume reductions were observed in the head of the caudate nucleus, globus pallidus, putamen, thalamus, and substantia nigra of WD patients (P < 0.001). Susceptibility values were negatively correlated with the volumes of the head of the caudate nucleus (r p = -0.657, P = 0.037), putamen (r p = -0.667, P = 0.037), and thalamus (r p = -0.613, P = 0.046) in WD patients. UWDRS neurological subscores were positively correlated with the susceptibility values of all examined DGM. The susceptibility values of putamen, head of the caudate nucleus, and dentate nucleus could well predict UWDRS neurological subscores. CONCLUSION: Our study provided in vivo evidence that paramagnetic metal accumulation in the DGM was associated with DGM atrophy and neurological impairment. The susceptibility of DGM could be used as a biomarker to assess the severity of neurodegeneration in WD.

Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease.

BACKGROUND: Currently, no study has evaluated metal accumulation in the brains of patients with Wilson's disease by using quantitative susceptibility mapping at 3T MRI. The objectives of this study were to qualitatively and quantitatively evaluate changes in magnetic susceptibility and R2* maps in deep gray matter nuclei to discriminate Wilson's disease patients from healthy controls and to evaluate their sensitivities in diagnosing Wilson's disease. METHODS: Magnetic susceptibility and R2* maps and conventional T1-weighted, T2-weighted, and T2-weighted fluid-attenuated inversion recovery images were obtained from 17 Wilson's disease patients and 14 age-matched healthy controls on a 3T MRI scanner. Differences between Wilson's disease and healthy control groups in susceptibility and R2* values in multiple deep nuclei were evaluated using a Mann-Whitney U test and receiver operating characteristic curves. The correlations of susceptibility and R2* values with Unified Wilson's Disease Rating Scale score were also performed. RESULTS: Magnetic susceptibility and R2* can effectively distinguish different types of signal abnormalities. Magnetic susceptibility and R2* values in multiple deep nuclei of Wilson's disease patients were significantly higher than those in healthy controls. Magnetic susceptibility value in the substantia nigra had the highest area under the curve (0.888). There were positive correlations of the Unified Wilson's Disease Rating Scale score with susceptibility values in the caudate nucleus (r = 0.757, P = 0.011), putamen (r = 0.679, P = 0.031), and red nucleus (r = 0.638, P = 0.047), as well as R2* values in the caudate nucleus (r = 0.754, P = 0.012). CONCLUSIONS: Quantitative susceptibility mapping at 3T could be a useful tool to evaluate metal accumulation in deep gray matter nuclei of Wilson's disease patients. © 2020 International Parkinson and Movement Disorder Society.

3D texture analyses within the substantia nigra of Parkinson's disease patients on quantitative susceptibility maps and R2∗ maps.

Iron accumulation in the substantia nigra (SN) is spatially heterogeneous, yet no study has quantitatively evaluated how the texture of quantitative susceptibility maps (QSM) and R2∗ might evolve with Parkinson's disease (PD) and healthy controls (HC). The aim of this study was to discriminate between patients with PD and HC using texture analysis in the SN from QSM and R2∗ maps. QSM and R2∗ maps were obtained from 28 PD patients and 28 HC on a clinical 3T MR imaging scanner using 3D multi-echo gradient-echo sequence. The first- and second- order texture features of the QSM and R2∗ images were obtained to evaluate group differences using two-tailed t-test. After correction for multiple comparisons, for the first-order analysis, the susceptibility of SN from patients with PD was significantly greater (p = 0.017) compared with the SN from HC. For the second-order texture analysis, angular second moment, entropy, and sum of entropy showed significant differences in QSM (p < 0.001) and R2∗ maps (p < 0.01). In addition, correlation, contrast, sum of variance and difference of variance, significantly separated the subject groups in QSM maps (p < 0.05) but not in R2∗ images. Receiver operating characteristic analysis showed that entropy and sum of entropy of the QSM maps in the SN yielded the highest performance for differentiating PD patients from HC (area under the curve = 0.89). In conclusion, most first- and second- order QSM texture features successfully distinguished PD patients from HC and significantly outperformed R2∗ texture analysis. The second-order texture features were more accurate and sensitive than first-order texture features for classifying PD patients.