Prognostic Assessment in Patients With Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Using MRI-Based Radiomics.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) carries a poor prognosis. Radiomics may hold potential value in prognostic assessment. PURPOSE: To develop and validate an MRI-based radiomics model and combine it with clinical factors to assess progression-free survival (PFS) and overall survival (OS) of patients with PCNSL. STUDY TYPE: Retrospective and prospective. POPULATION: Three hundred seventy-nine patients (179 female, 53 ± 7 years) from 2014 to 2022. FIELD STRENGTH/SEQUENCE: T2/fluid-attenuated inversion recovery, contrast-enhanced T1WI and diffusion-weighted echo-planar imaging sequences on 3.0 T. ASSESSMENT: Radiomics features were extracted from enhanced tumor regions on preoperative multi-sequence MRI. Using a least absolute shrinkage and selection operator (LASSO) Cox regression model to select radiomic signatures in training cohort (N = 169). Cox proportional hazards models were constructed for clinical, radiomics, and combined models, with internal (N = 72) and external (N = 32) cohorts validating model performance. STATISTICAL TESTS: Chi-squared, Mann-Whitney, Kaplan-Meier, log-rank, LASSO, Cox, decision curve analysis, time-dependent Receiver Operating Characteristic, area under the curve (AUC), and likelihood ratio test. P-value <0.05 was considered significant. RESULTS: Follow-up duration was 28.79 ± 22.59 months (median: 25). High-risk patients, determined by the median radiomics score, showed significantly lower survival rates than low-risk patients. Compared with NCCN-IPI, conventional imaging and clinical models, the combined model achieved the highest C-index for both PFS (0.660 internal, 0.802 external) and OS (0.733 internal, 0.781 external) in validation. Net benefit was greater with radiomics than with clinical alone. The combined model exhibited performance with AUCs of 0.680, 0.752, and 0.830 for predicting 1-year, 3-year, and 5-year PFS, and 0.770, 0.789, and 0.863 for OS in internal validation, with PFS AUCs of 0.860 and 0.826 and OS AUCs of 0.859 and 0.748 for 1-year and 3-year survival in external validation. DATA CONCLUSION: Incorporating a multi-sequence MR-based radiomics model into clinical models enhances the assess accuracy for the prognosis of PCNSL. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Gamma-aminobutyric acid supplementation improves olanzapine-induced insulin resistance by inhibiting macrophage infiltration in mice subcutaneous adipose tissue.

AIMS: To investigate whether gamma-aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms. MATERIALS AND METHODS: Insulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration. RESULTS: We found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine-induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine-induced adipose tissue macrophage infiltration and M1-like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine-induced insulin resistance at least in part through a GABAB receptor-dependent pathway. CONCLUSIONS: These findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine-induced metabolic disorders.

Tigroid Enhancement: A Characteristic Enhancement Pattern of the Cerebellar Hemisphere on MRI With Intracranial Dural Arteriovenous Fistulas.

PURPOSE: This study aims to investigate a characteristic cerebellar hemisphere enhancement pattern on magnetic resonance imaging (MRI) that could aid in early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). MATERIALS AND METHODS: Pretreatment MR images of 57 patients with intracranial DAVFs between January 1, 2017, and February 28, 2023, were retrospectively analyzed. A total of 128 patients with confirmed alternative cerebellar lesions during the same period were included as a control group. All patients underwent enhanced MRI with a 3.0T scanner. The presence or absence of parallel enhanced linear striations on the surface of the cerebellar lesions was documented. Statistically significant differences were determined by the Fisher exact test. RESULTS: Cerebellar lesions were identified in 4 intracranial DAVF patients (7.0%). All 4 patients were male, with an average age of 64 years (range: 58-76 years). The pretreatment MR images of all 4 DAVF patients with cerebellar lesions demonstrated the characteristic tigroid enhancement pattern. Tortuous flow voids were present in the MR images of 3 of the 4 patients. Tigroid enhancement pattern was not observed in the remaining 53 intracranial DAVF patients and all control patients. The differences in the incidence of the pattern were significant (p=0.01). CONCLUSION: A characteristic tigroid enhancement pattern of the cerebellar hemisphere on MRI may aid in the early and specific diagnosis of intracranial DAVFs, allowing timely treatment and improving outcomes. CLINICAL IMPACT: The identification of a characteristic tigroid enhancement pattern on MRI for cerebellar hemisphere lesions holds significant promise for clinical practice. This pattern serves as a distinctive marker aiding in the early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). Clinicians can now utilize this innovative finding to expedite diagnostic workflows, enabling timely intervention and management strategies. The incorporation of this novel imaging feature enhances diagnostic accuracy, potentially reducing misdiagnosis rates and preventing delays in treatment initiation. Ultimately, this advancement may lead to improved patient outcomes and quality of care in neurosurgical and neuroradiological practice.

A review of the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle.

In the past few decades, genomic selection and other refined strategies have been used to increase the growth rate and lean meat production of beef cattle. Nevertheless, the fast growth rates of cattle breeds are often accompanied by a reduction in intramuscular fat (IMF) deposition, impairing meat quality. Transcription factors play vital roles in regulating adipogenesis and lipogenesis in beef cattle. Meanwhile, understanding the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle has gained significant attention to increase IMF deposition and meat quality. Therefore, the aim of this paper was to provide a comprehensive summary and valuable insight into the complex role of transcription factors in adipogenesis and lipogenesis in beef cattle. This review summarizes the contemporary studies in transcription factors in adipogenesis and lipogenesis, genome-wide analysis of transcription factors, epigenetic regulation of transcription factors, nutritional regulation of transcription factors, metabolic signalling pathways, functional genomics methods, transcriptomic profiling of adipose tissues, transcription factors and meat quality and comparative genomics with other livestock species. In conclusion, transcription factors play a crucial role in promoting adipocyte development and fatty acid biosynthesis in beef cattle. They control adipose tissue formation and metabolism, thereby improving meat quality and maintaining metabolic balance. Understanding the processes by which these transcription factors regulate adipose tissue deposition and lipid metabolism will simplify the development of marbling or IMF composition in beef cattle.

Chromosome-level genome assembly for takin (Budorcas taxicolor) provides insights into its taxonomic status and genetic diversity.

The takin (Budorcas taxicolor) is one of the largest bovid herbivores in the subfamily Caprinae. The takin is at high risk of extinction, but its taxonomic status and genetic diversity remain unclear. In this study, we constructed the first reference genome of Bu. taxicolor using PacBio long High-Fidelity reads and Hi-C technology. The assembled genome is ~2.95 Gb with a contig N50 of 68.05 Mb, which were anchored onto 25+XY chromosomes. We found that the takin was more closely related to muskox than to other Caprinae species. Compared to the common ancestral karyotype of bovidae (2n = 60), we found the takin (2n = 52) experienced four chromosome fusions and one large translocation. Furthermore, we resequenced nine golden takins from the main distribution area, the Qinling Mountains, and identified 3.3 million single nucleotide polymorphisms. The genetic diversity of takin was very low (θπ = 0.00028 and heterozygosity =0.00038), among the lowest detected in domestic and wild mammals. Takin genomes showed a high inbreeding coefficient (FROH =0.217), suggesting severe inbreeding depression. The demographic history showed that the effective population size of takins declined significantly from ~100,000 years ago. Our results provide valuable information for protection of takins and insights into their evolution.

Molecular immuno-imaging improves tumor detection in head and neck cancer.

Detection and accurate delineation of tumor is important for the management of head and neck squamous cell carcinoma (HNSCC) but is challenging with current imaging techniques. In this study, we evaluated whether molecular immuno-imaging targeting myeloperoxidase (MPO) activity, an oxidative enzyme secreted by many myeloid innate immune cells, would be superior in detecting tumor extent compared to conventional contrast agent (DTPA-Gd) in a carcinogen-induced immunocompetent HNSCC murine model and corroborated in human surgical specimens. In C57BL/6 mice given 4-nitroquinoline-N-oxide (4-NQO), there was increased MPO activity in the head and neck region as detected by luminol bioluminescence compared to that of the control group. On magnetic resonance imaging, the mean enhancing volume detected by the MPO-targeting agent (MPO-Gd) was higher than that by the conventional agent DTPA-Gd. The tumor volume detected by MPO-Gd strongly correlated with tumor size on histology, and higher MPO-Gd signal corresponded to larger tumor size found by imaging and histology. On the contrary, the tumor volume detected by DTPA-Gd did not correlate as well with tumor size on histology. Importantly, MPO-Gd imaging detected areas not visualized with DTPA-Gd imaging that were confirmed histopathologically to represent early tumor. In human specimens, MPO was similarly associated with tumors, especially at the tumor margins. Thus, molecular immuno-imaging targeting MPO not only detects oxidative immune response in HNSCC, but can better detect and delineate tumor extent than nonselective imaging agents. Thus, our findings revealed that MPO imaging could improve tumor resection as well as be a useful imaging biomarker for tumor progression, and potentially improve clinical management of HNSCC once translated.

Analysis of lncRNAs profiles associated with ferroptosis can predict prognosis and immune landscape and drug sensitivity in patients with clear cell renal cell carcinoma.

Ferroptosis is a novel kind of iron- and reactive oxygen-induced cell death, investigation into ferroptosis-associated long noncoding RNAs (FALs) in clear cell renal cell carcinoma (ccRCC) is scarce. The goal of the research was to look at FALs' possible predictive significance, as well as their interaction with the immune microenvironment and therapeutic responsiveness of ccRCC. The Cancer Genome Atlas database was employed to retrieve RNA sequencing data from 530 individuals with ccRCC. Patients with ccRCC were randomly assigned to one of two groups: training or testing. Pearson's correlation analysis through the identified ferroptosis-related genes was implemented to screen for FALs. Finally, a FALs signature composed of eight lncRNAs was discovered for predicting survival outcomes in ccRCC patients. ccRCC patients in the training, testing, and overall cohorts were separated into low-risk and high-risk groups based on their risk score. The FALs signature was identified to be an independent factor for overall survival in the multivariate Cox analysis (hazard ratio = 1.013, 95% confidence interval = 1.008-1.018, p < 0.001). A clinically prognostic nomogram was created depending on the FALs signature and clinical characteristics. The nomogram provides greater clinical practicability and may reliably estimate patients' overall survival. The FALs signature may additionally precisely represent ccRCC's immunological environment, immunotherapy reaction, and drug sensitivity. The eight FALs and their signature provide precise and reliable methods for evaluating the clinical effects of in ccRCC patients, and they could be biological markers and targets for therapy.

YOLO-Weld: A Modified YOLOv5-Based Weld Feature Detection Network for Extreme Weld Noise.

Weld feature point detection is a key technology for welding trajectory planning and tracking. Existing two-stage detection methods and conventional convolutional neural network (CNN)-based approaches encounter performance bottlenecks under extreme welding noise conditions. To better obtain accurate weld feature point locations in high-noise environments, we propose a feature point detection network, YOLO-Weld, based on an improved You Only Look Once version 5 (YOLOv5). By introducing the reparameterized convolutional neural network (RepVGG) module, the network structure is optimized, enhancing detection speed. The utilization of a normalization-based attention module (NAM) in the network enhances the network's perception of feature points. A lightweight decoupled head, RD-Head, is designed to improve classification and regression accuracy. Furthermore, a welding noise generation method is proposed, increasing the model's robustness in extreme noise environments. Finally, the model is tested on a custom dataset of five weld types, demonstrating better performance than two-stage detection methods and conventional CNN approaches. The proposed model can accurately detect feature points in high-noise environments while meeting real-time welding requirements. In terms of the model's performance, the average error of detecting feature points in images is 2.100 pixels, while the average error in the world coordinate system is 0.114 mm, sufficiently meeting the accuracy needs of various practical welding tasks.

Research Progress of Dihydroquercetin in the Treatment of Skin Diseases.

Skin is a barrier to maintaining the stability of the human environment and preventing the invasion of pathogens. When skin tissue is exposed to the external environment, it will inevitably develop defects due to trauma, injury, burns, ulcers, surgery, and chronic diseases. Rapid skin repair is the key to reducing infection, relieving pain, and improving quality of life. Dihydroquercetin is a kind of flavonoid that has a wide range of pharmacological activities and can improve skin repair, skin inflammation, skin cancer, and so on. In this paper, the application of dihydroquercetin in medical dressings and the research progress in the treatment of skin-related diseases are reviewed, so as to provide reference for further developing dihydroquercetin as a drug for the treatment of skin diseases.

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder.

PURPOSE: To develop and validate a population pharmacokinetic (PPK) model of valproic acid (VPA) in adult Chinese patients with bipolar disorder, and provide guidance for individualized therapy in this population. METHODS: A total of 1104 serum concentrations from 272 patients were collected in this study. The data analysis was performed using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, biological characteristics, and concomitant medications. Bootstrap validation (1000 runs), normalized prediction distribution error (NPDE), and external validation of 50 patients were employed to evaluate the final model. RESULTS: A one-compartment model with first-order absorption and elimination was developed for VPA extended-release tablets. VPA clearance was significantly influenced by three variables: sex (12% higher in male patients), daily dose (increasing with the 0.13 exponent), and body weight (increasing with the 0.56 exponent). Typical values for the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) for a female patient weighing 70 kg administered VPA 1000 mg/day were 0.18 h-1, 0.46 L/h, and 12.84 L, respectively. The results of model evaluation indicated a good stable and precise performance of the final model. CONCLUSIONS: A qualified PPK model of VPA was developed in Chinese patients with bipolar disorder. This model could be used as a suitable tool for the personalization of VPA dosing for bipolar patients.

RNA-seq reveal role of bovine TORC2 in the regulation of adipogenesis.

Low intramuscular adipose tissue (marbling) continues to be challenge for improving beef quality in Chinese cattle. Highly marbled meat is very desirable; hence, methods to increase IMF content have become a key aspect of improving meat quality. Therefore, research on the mechanism of adipogenesis provides invaluable information for the improvement of meat quality. This study investigated the effect of TORC2 and its underlying mechanism on lipid metabolism in bovine adipocytes. The TORC2 gene was downregulated in bovine adipocytes by siRNA, and RNA sequencing was performed. Downregulation of TORC2 negatively affected bovine adipocyte differentiation. In addition, a total of 577 DEGs were found, containing 146 up-regulated and 376 down-regulated genes. KEGG pathway analysis revealed that the DEGs were linked with neuroactive ligand-receptor interaction pathway, calcium signaling pathway, cAMP pathway, chemokine signaling pathway and Wnt signaling pathway. Gene Ontology (GO) term analysis of the DEGs showed that down-regulation of TORC2 gene significantly suppressed the genes regulating important GO terms of adipogenesis-related processes in bovine adipocytes, especially regulation of biological activity, regulation of primary metabolic process, regulation of multicellular organismal process, cell adhesion, lipid metabolic process, secretion, chemical homeostasis, regulation of transport, cell-cell signaling, cAMP metabolic process, cellular calcium ion homeostasis, fat cell differentiation, and cell maturation. In conclusion, our results suggest that TORC2 at least in part regulates lipid metabolism in bovine adipocytes. The results of this study provide a basis for studying the function and molecular mechanism of the TORC2 gene in regulating adipogenesis.

Genetic Architecture and Selection of Chinese Cattle Revealed by Whole Genome Resequencing.

The bovine genetic resources in China are diverse, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Chinese cattle, we analyzed the whole genomes of 46 cattle from six phenotypically and geographically representative Chinese cattle breeds, together with 18 Red Angus cattle genomes, 11 Japanese black cattle genomes and taurine and indicine genomes available from previous studies. Our results showed that Chinese cattle originated from hybridization between Bos taurus and Bos indicus. Moreover, we found that the level of genetic variation in Chinese cattle depends upon the degree of indicine content. We also discovered many potential selective sweep regions associated with domestication related to breed-specific characteristics, with selective sweep regions including genes associated with coat color (ERCC2, MC1R, ZBTB17, and MAP2K1), dairy traits (NCAPG, MAPK7, FST, ITFG1, SETMAR, PAG1, CSN3, and RPL37A), and meat production/quality traits (such as BBS2, R3HDM1, IGFBP2, IGFBP5, MYH9, MYH4, and MC5R). These findings substantially expand the catalogue of genetic variants in cattle and reveal new insights into the evolutionary history and domestication traits of Chinese cattle.

Myeloperoxidase Molecular MRI Reveals Synergistic Combination Therapy in Murine Experimental Autoimmune Neuroinflammation.

Background Despite advances in immunomodulatory agents, most current therapies for multiple sclerosis target lymphocytes or lymphocytic function. However, therapy response may be less than optimal due to demyelination and axonal damage caused by myeloid cells. Purpose To determine if myeloperoxidase (MPO) molecular MRI can evaluate whether combination therapy targeting both lymphoid and myeloid inflammation can improve autoimmune neuroinflammation compared with either drug alone, even at suboptimal doses. Materials and Methods Four groups of 94 female mice (8-10 weeks old) were induced with experimental autoimmune encephalomyelitis (EAE) from August 2, 2016, to March 30, 2018, and divided into saline control (n = 22), 4-aminobenzoic acid hydrazide (ABAH) therapy group (n = 19), glatiramer acetate (GA) therapy group (n = 22), and combination therapy group (n = 31). Mice were administered suboptimal doses of ABAH, an irreversible inhibitor of MPO; GA, a first-line multiple sclerosis drug; both ABAH and GA; or saline (control). Mice were imaged with bis-5-hydroxytryptamide-diethylenetriaminepentaacetate gadolinium (hereafter, MPO-Gd) MRI. One-way analysis of variance, two-way analysis of variance, Kurskal-Wallis, and log-rank tests were used. P < .05 was considered to indicate statistical significance. Results The combination-treated group showed delayed disease onset (day 11.3 vs day 9.8 for ABAH, day 10.4 for GA, day 9.9 for control; P < .05) and reduced disease severity (clinical score during the acute exacerbation period of 1.8 vs 3.8 for ABAH, 3.1 for GA, 3.9 for control; P < .05). The combination-treated group demonstrated fewer MPO-positive lesions (30.2 vs 73.7 for ABAH, 64.8 for GA, 67.2 for control; P < .05), smaller MPO-positive lesion volume (16.7 mm3 vs 65.2 mm3 for ABAH, 69.9 mm3 for GA, 66.0 mm3 for control; P < .05), and lower intensity of MPO-Gd lesion activation ratio (0.7 vs 1.9 for ABAH, 3.2 for GA, 2.3 for control; P < .05). Reduced disease severity in the combination group was confirmed at histopathologic analysis, where MPO expression (1779 vs 2673 for ABAH, 2898 for GA; P < .05) and demyelination (5.3% vs 9.0% for ABAH, 10.6% for GA; P < .05) were ameliorated. Conclusion Myeloperoxidase molecular MRI can track the treatment response from immunomodulatory drugs even if the drug does not directly target myeloperoxidase, and establishes that combination therapy targeting both myeloid and lymphocytic inflammation is effective for murine autoimmune neuroinflammation, even at suboptimal doses. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Walczak in this issue.

A New-Designed Lung-Bending Device for Bronchoscopic Lung Volume Reduction of Severe Emphysema: A Feasibility Study in Pigs.

BACKGROUND: Bronchoscopic therapies are less invasive alternatives of surgical lung volume reduction for severe emphysema. Bending of lung tissue by implanting metallic coils into bronchi is one of the procedures. A new-designed device with a similar rationale, Reverser, has been developed with some improvements. OBJECTIVES: The aim of the study was to evaluate the safety and feasibility of the Reversers. METHODS: Twelve healthy pigs were randomly divided into 3 groups (groups A, B, and C). The Reversers were implanted bronchoscopically into the selected airways using a proprietary delivery system. Physical examination, chest fluoroscopy, computed tomography (CT) scans, and bronchoscopic observations were performed before implantation and during the follow-up period. Necropsy was performed respectively at 1 month (group A), 3 months (group B), and 6 months (group C) after implantation. RESULTS: A total of 47 Reversers were implanted successfully. The procedure was feasible and well tolerated by all pigs. No severe complications, such as pneumothorax, abscesses, and airway hemorrhage, were found. No unintended injuries or death occurred. Mild granulation and inflammation were observed in the airway wall. Opacities around Reversers were shown on CT scans in some pigs. In the pigs with opacities, histological evaluation revealed widened alveolar septa due to inflammatory cell infiltration in the vicinity of the Reversers. On the analysis of CT data, there was a trend for volume reduction of the treated lung at 1 and 3 months after treatment compared with baseline. CONCLUSIONS: This study showed that Reversers were safe and feasible for bronchoscopic lung volume reduction in pigs.

Clinical features of patients with anti-leucine-rich glioma inactivated-1 protein associated encephalitis: a Chinese case series.

Purpose: Antibodies against leucine-rich glioma inactivated 1 (LGI1) are associated with limbic encephalitis and faciobrachial dystonic seizures (FBDS). We present a large series of Han Chinese patients for further clinical refinement. Materials and methods: Serum and cerebrospinal fluid samples from patients were tested. Clinical information of patients with serum anti­LGI1antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results: The median onset age of the 24 patients was 56.9 years. Among these cases, 18 (75%) patients presented with new­onset refractory seizures, 18 (75%) patients had memory deficits, eight (33.3%) patients had a personality changes and five (20.8%) patients had a disturbance of consciousness. FBDS was observed in nine (37.5%) patients and five of them presented with FBDS as the initial symptom. No cancer was detected in any patient by CT scans. Fourteen (58.3%) patients had hyponatremia. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in four (16.7%) and six (25%) patients, respectively. Twelve (50%) patients showed paroxysmal sharp/spike waves and slow waves on EEG and seven (29.2%) patients showed mesial temporal region abnormalities by MRI scans. All patients received antiepileptic drugs and immunotherapy. After treatments, the modified Rankin scores of all patients were decreased. Conclusions: Our study showed that Han Chinese patients with anti­LGI1 antibody associated encephalitis had prominent clinical manifestations including seizures, memory deficits and FBDS. They showed neurological improvement with timely immunotherapy. Prompt treatments after rapid clinical recognition is important to improve the prognosis of patients.

Transcriptional Regulation by CpG Sites Methylation in the Core Promoter Region of the Bovine SIX1 Gene: Roles of Histone H4 and E2F2.

DNA methylation is a major epigenetic modification of the genome and has an essential role in muscle development. The SIX1 gene is thought to play a principal role in mediating skeletal muscle development. In the present study, we determined that bovine SIX1 expression levels were significantly higher in the fetal bovine group (FB) and in undifferentiated Qinchuan cattle muscle cells (QCMCs) than in the adult bovine group (AB) and in differentiated QCMCs. Moreover, a bisulfite sequencing polymerase chain reaction (BSP) analysis of DNA methylation levels showed that three CpG sites in the core promoter region (-216/-28) of the bovine SIX1 gene exhibited significantly higher DNA methylation levels in the AB and differentiated QCMCs groups. In addition, we found that DNA methylation of SIX1 core promoter in vitro obviously influences the promoter activities. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay, in combination with site-directed mutation and siRNA interference, demonstrated that histone H4 and E2F2 bind to the -216/-28 region and play important roles in SIX1 methylation regulation during development. The results of this study provide the foundation for a better understanding of the regulation of bovine SIX1 expression via methylation and muscle developmental in beef cattle.

Effect of childhood trauma on cognitive functions in a sample of Chinese patients with schizophrenia.

In this study, we aimed to determine the influence of various types of childhood trauma (CT) on cognitive functions in Chinese patients presented with schizophrenia. One hundred sixty-two patients were assessed with the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We investigated the correlations between various types of CT, demographic characteristics, and cognitive functions. Significant negative correlations were observed in physical abuse (PA) and sexual abuse (SA) with the language score (r=-0.190, -0.216, respectively, p<0.05). Similarly, physical neglect (PN) and the total score of CTQ were negatively correlated with the attention score (r=-0.17, -0.206, p<0.05, respectively) as well as the total RBANS score (r=-0.199, -0.223, respectively P<0.05). PN was also negatively correlated with delayed memory (r=-0.167, p<0.05). Regressions analysis indicated significant negative correlations between PN and attention, as well as the cognitive total score (p<0.001). Furthermore, demographic variables (years of education, family income) and clinical characteristics (type of anti-psychotics, duration of illness and times of recurrence) were correlated with cognitive functions. The current study showed that different types of CT could impact specific cognitive functions in Chinese schizophrenia patients. Therefore, we recommend that trauma-focused mental interventions for schizophrenia patients should be developed and routinely offered to patients.

Surface biotinylation of cytotoxic T lymphocytes for in vivo tracking of tumor immunotherapy in murine models.

Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0.05). Incubation temperature was not a key factor. CTLs maintained sufficient labeling for at least 72 h (P < 0.05), without altering cell viability. After co-culturing labeled CTLs with mouse glioma stem cells (GSCs) engineered to present biotin on their surface, targeting CTLs could specifically target biotin-presenting GSCs and inhibited cell proliferation (P < 0.01) and tumor spheres formation. In a biotin-presenting GSC brain tumor model, targeting CTLs could be detected in biotin-presenting gliomas in mouse brains but not in the non-tumor-bearing contralateral hemispheres (P < 0.05). In vivo fluorescent molecular tomography imaging in a subcutaneous U87 mouse model confirmed that targeting CTLs homed in on the biotin-presenting U87 tumors but not the control U87 tumors. PET imaging with 89Zr-deferoxamine-biotin and SA showed a rapid clearance of the PET signal over 24 h in the control tumor, while only minimally decreased in the targeted tumor. Thus, sulfo-NHS-biotin-SA labeling is an efficient method to noninvasively track the migration of adoptive transferred CTLs and does not alter CTL viability or interfere with CTL-mediated cytotoxic activity.

Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia: A Prospective, Multicenter Study.

The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms-Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment.

Tissue expression analysis, cloning and characterization of the 5'-regulatory region of the bovine FABP3 gene.

Fatty acid binding protein 3 (FABP3) is a member of the FABP family which bind fatty acids and have an important role in fatty acid metabolism. A large number of studies have shown that the genetic polymorphisms of FABP3 are positively correlated with intramuscular fat (IMF) content in domestic animals, however, the function and transcriptional characteristics of FABP3 in cattle remain unclear. Real-time PCR analysis revealed that bovine FABP3 was highly expressed in cardiac tissue. The 5'-regulatory region of bovine FABP3 was cloned and its transcription initiation sites were identified. Sequence analysis showed that many transcriptional factor binding sites including TATA-box and CCAAT-box were present on the 5'-flanking region of bovine FABP3, and four CpG islands were found on nucleotides from -891 to +118. Seven serial deletion constructs of the 5'-regulatory region evaluated in dual-luciferase reporter assay indicated that its core promoter was 384 base pairs upstream from the transcription initiation site. The transcriptional factor binding sites RXRα, KLF15, CREB and Sp1 were conserved in the core promoter of cattle, sheep, pigs and dogs. These results provide further understanding of the function and regulation mechanism of bovine FABP3.