Integrated ubiquitomics characterization of hepatocellular carcinomas.

BACKGROUND AND AIMS: Patients with aggressive hepatocellular carcinoma (HCC) have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. APPROACH AND RESULTS: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 HCC patients. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1 and LAMA4 were highly expressed in the DFS poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed crosstalk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to AKT-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. CONCLUSIONS: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.

A practical risk stratification system based on ultrasonography and clinical characteristics for predicting the malignancy of soft tissue masses.

OBJECTIVE: To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy. METHODS: This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally. RESULTS: The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001-0.008), low suspicion (FP: 0.008-0.365), moderate suspicion (FP: 0.189-0.911), and high suspicion (FP: 0.798-0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively. CONCLUSION: The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients. CRITICAL RELEVANCE STATEMENT: With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management. KEY POINTS: There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management.

Coupling of Paleosedimentary Environment and Lithofacies: Implications for Shale Oil Enrichment in the Lianggaoshan Formation, Northeastern Sichuan Basin, China.

The sedimentary environment is paramount in dictating depositional processes, ecological settings, and hydrodynamic conditions, all of which are pivotal to the aggregation of organic-rich sediments. A synergistic interplay is observed among the paleosedimentary environment, lithofacies, and enrichment of shale oil. Utilizing an analysis of elemental geochemistry and organic geochemical parameters-such as total organic carbon (TOC) content-this study endeavors to identify the predominant factors that govern the enrichment of organic matter (OM). It reconstructs the evolutionary trajectory of the paleosedimentary environment and introduces a dynamic model for shale oil enrichment within the Jurassic Lianggaoshan Formation of the Sichuan Basin. The results indicate that the Lianggaoshan Formation shale can be categorized into five lithological types, including high TOC felsic-rich shale (A), moderate TOC felsic-rich shale (B), moderate TOC felsic-rich mudstone (C), low TOC felsic-rich shale (D), and low TOC felsic-rich mudstone (E), and high TOC felsic-rich shale has the highest TOC and oil content. The shales of the Lianggaoshan Formation were deposited in an environment characterized by abundant terrestrial input, humid climate, freshwater conditions, reduced oxygen levels, and thriving primary productivity. OM enrichment is mainly controlled by the combination of a humid paleoclimate, high primary productivity, and other factors. The paleoenvironment deposited by lithofacies A coincides with the paleoenvironment conducive to OM enrichment, which makes lithofacies A become the dominant lithofacies for shale oil enrichment. Additionally, the sedimentary environment evolution characteristics and shale oil enrichment model of the Lianggaoshan Formation were established based on geochemical parameters. The paleosedimentary environment of the Lianggaoshan Formation from bottom to top is more and more unfavorable. The No.1 submember of the Lianggaoshan Formation is the most potential shale submember for shale oil exploration due to the paleosedimentary environment that promoted the deposition of lithofacies A and OM enrichment.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Network structure of complex interactions of premenstrual syndrome and influencing factors in young adult women.

BACKGROUND: In the transition phase from adolescence to adulthood, premenstrual syndrome (PMS) occurs more commonly, with a variety of symptoms. The occurrence of PMS may be the result of a combination of demographic, physiological, psychological and sociological factors. This study aimed to identify the central symptoms of PMS, and explored the complex influencing factors especially the one-to-one inter-relationships factors with specific symptoms. METHOD: This is a cross-sectional study conducted in mainland China. 3458 young adult women were assessed. Using the Premenstrual Syndrome Scale (PSS) to assess the PMS, and PSS score was over 6 divided into PMS group, and vice versa. Influencing factors were assessed by a set of self-reported questionnaire. Network analysis was used to examined the interplay of PMS, whilst also considering the influencing factors of PMS. RESULTS: In summary, 1479 participants were in PMS group. Anxiety had the highest strength centrality (1.12/1.09), shown higher centrality in the both network. Swelling of the hands or feet also shown higher strength centrality (0.89) in PMS group. PMS is associated with a higher history of dysmenorrhea, and neurotic personality. Neurotic personality - depressed mood/nervousness (0.27/0.23), history of dysmenorrhea - abdominal distension (0.21), had significantly higher weight than other edges in PMS group. CONCLUSION: Anxiety was the most central symptom in the network, and was closely associated with other symptoms like depressed mood, which provided additional evidence for the centrality of emotional features in PMS. Moreover, the influencing factors of PMS combined demographic, physiological, psychological, and sociological factors. According to the central symptoms and factors affecting the specific PMS symptoms in young adult women, targeted intervention is helpful to prevent and alleviate PMS. LIMITATION: Cross-sectional design cannot infer the directionality of the associations between variables. All data is self-reported with recall bias and the edge weights across the constructs of influencing factors and PMS were fairly small.

Functional disruptions of the brain network in low back pain: a graph-theoretical study.

PURPOSE: The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. METHODS: Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. RESULTS: At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. CONCLUSION: This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches.

Altered habenular connectivity in chronic low back pain: An fMRI and machine learning study.

The habenula has been implicated in the pathogenesis of pain and analgesia, while evidence concerning its function in chronic low back pain (cLBP) is sparse. This study aims to investigate the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 52 patients with cLBP and 52 healthy controls (HCs) and assess the feasibility of distinguishing cLBP from HCs based on connectivity by machine learning methods. Our results indicated significantly enhanced rsFC of the habenula-left superior frontal cortex (SFC), habenula-right thalamus, and habenula-bilateral insular pathways as well as decreased rsFC of the habenula-pons pathway in cLBP patients compared to HCs. Dynamic causal modelling revealed significantly enhanced effective connectivity from the right thalamus to right habenula in cLBP patients compared with HCs. RsFC of the habenula-SFC was positively correlated with pain intensities and Hamilton Depression scores in the cLBP group. RsFC of the habenula-right insula was negatively correlated with pain duration in the cLBP group. Additionally, the combination of the rsFC of the habenula-SFC, habenula-thalamus, and habenula-pons pathways could reliably distinguish cLBP patients from HCs with an accuracy of 75.9% by support vector machine, which was validated in an independent cohort (N = 68, accuracy = 68.8%, p = .001). Linear regression and random forest could also distinguish cLBP and HCs in the independent cohort (accuracy = 73.9 and 55.9%, respectively). Overall, these findings provide evidence that cLBP may be associated with abnormal rsFC and effective connectivity of the habenula, and highlight the promise of machine learning in chronic pain discrimination.

The ovine HIAT1 gene: mRNA expression, InDel mutations, and growth trait associations.

Background: The hippocampal abundant transcript 1 (HIAT1) gene, also known as major facilitator superfamily domain-containing 14A (MFSD14A), encodes for a transmembrane transporter protein and has been previously shown to be associated with milk production in buffalo and sheep breeds, as well as growth traits in chicken and goats. However, tissue level distribution of the ovine HIAT1 gene, as well as its effect on body morphometric traits in sheep, has yet to be studied. Methods: The HIAT1 mRNA expression profile of Lanzhou fat-tailed (LFT) sheep was determined by quantitative real-time PCR (qPCR). A total of 1498 sheep of three indigenous Chinese sheep breeds were PCR-genotyped for polymorphisms of HIAT1 gene. Student's t-test was used to observe the association between the genotype and sheep morphometric traits. Results: HIAT1 was widely expressed in all examined tissues, and was particularly abundant in the testis of male LFT sheep. Additionally, a 9-bp insertion mutation (rs1089950828) located within the 5'-upstream region of HIAT1 was investigated in Luxi black-headed (LXBH) sheep and Guiqian semi-fine wool (GSFW) sheep. The wildtype allele frequency 'D' was found to be more prevalent than that of the mutant allele 'I'. Furthermore, low genetic diversity was confirmed in all sampled sheep populations. Subsequent association analyses indicated an association between the 9-bp InDel mutation of interest and the morphometric traits of LXBH and GSFW sheep. Furthermore, yearling ewes with a heterozygous genotype (ID) demonstrated smaller body sizes, while yearling rams and adult ewes with the heterozygous genotype were found to have overall better growth performance. Conclusion: These findings imply that functional InDel polymorphism (rs1089950828) has the potential to be utilized for marker-assisted selection (MAS) of growth traits in domestic Chinese sheep populations.

A 14-bp deletion in bovine EPAS1 gene is associated with carcass traits.

EPAS1 (Endothelial PAS Domain Protein 1) gene is well-known for its function in plateau hypoxia adaptability. It encodes HIF-2α, which involved in the induction of genes regulated by oxygen and then affects multiple physiological processes such as angiogenesis and energy metabolism. All of these indicate it may affect the development of animals. In this study, a 14-bp deletion in EPAS1 gene was uncovered in Shandong black cattle population (n = 502). Two genotypes (II and ID) were found and the frequency of the homozygous II genotype is higher than the heterozygous ID genotype. This population is consisted with HWE (p > 0.05). And more importantly, the 14-bp deletion was associated with outside flat (p = 0.003), brisket (p = 0.001), and knuckle (p = 0.032). These findings suggested that the 14-bp deletion is significantly associated with carcass traits, which could be served as a molecular marker applied to cow breeding.

Psychosocial resources moderate the association between stress and insomnia among patients with digestive system cancers.

This study explored the profiles of psychosocial resources combined with resilience and family care, and analyzed their moderating effects on the relationship between stress and insomnia in patients with digestive system cancers. A total of 366 patients were recruited to participate in this study from two tertiary hospitals in China. They were assessed using the Perceived Stress Scale - 4 items, Insomnia Severity Index, Family Concern Index Questionnaire, and 10-item Connor-Davidson Resilience Scale. Latent profile analysis and the BCH (Bolck, Croon & Hagenaars) method were used to identify the subtypes and estimate the moderating role of psychosocial coping resources. About 62.3% of participants had insomnia symptoms. Insomnia was positively correlated to the stress (r = 0.25, P < 0.001). The latent classes were the low resources class (32.8%), the medium resources class (46.1%), and high resources class (21.1%). Among these, in low (estimate value = 0.563, P = 0.003) and medium (estimate value = 0.301, P = 0.029) resources class, stress had an effect on insomnia. There was no association between stress and insomnia in high resources class (estimate value = 0.165, P = 0.637). Stress might be associated with to insomnia problems, whereas patients with high psychosocial resources are more not vulnerable. Interventions to improve family function and resilience could contribute to easing the insomnia of patients with digestive system cancers.

Screen of small fragment mutations within the sheep thyroid stimulating hormone receptor gene associated with litter size.

The thyroid stimulating hormone receptor (TSHR), a glycoprotein hormone receptor, plays an important role in metabolic regulation and photoperiod control in the time of reproduction in birds and mammals. Previous genome-wide association studies revealed that the TSHR gene was related to reproduction and its function was identified in female reproduction, but rare studies reported the polymorphism of TSHR gene. However, the molecular mutations of the TSHR gene in sheep have not been reported so far. Herein, we explored potential polymorphisms of the sheep TSHR gene, and a 29 bp nucleotide sequence variant (rs1089565492) was identified in the AUW sheep. There were three genotypes of the 29 bp variant locus detected which named 'II' 'DD' and 'ID' been identified. Association analysis results showed the 29 bp variant was significantly associated with the litter size of the AUW sheep (p < 0.05). This finding suggests that the 29 bp nucleotide sequence variant within TSHR gene could be a candidate marker of reproduction traits for sheep breeding improving through the marker-assisted selection (MAS).

Added value of contrast-enhanced ultrasound to conventional ultrasound for characterization of indeterminate soft-tissue tumors.

OBJECTIVE: To assess the added value of contrast-enhanced ultrasound (CEUS) to conventional ultrasound in differentiating benign soft-tissue tumors from malignant ones. METHODS: 197 soft-tissue tumors underwent ultrasound examination with confirmed histopathology were retrospectively evaluated. The radiologists classified all the tumors as benign, malignant, or indeterminate according to ultrasound features. The indeterminate tumors underwent CEUS were reviewed afterwards for malignancy identification by using individual and combined CEUS features. RESULTS: Ultrasound analysis classified 62 soft-tissue tumors as benign, 111 tumors as indeterminate and 24 tumors as malignant. There 104 indeterminate tumors were subject to CEUS. Three CEUS features including enlargement of enhancement area, infiltrative enhancement boundary, and intratumoral arrival time difference were significantly associated with the tumor nature in both univariable and multivariable analysis for the indeterminate tumors (all p < 0.05). When at least one out of the three discriminant CEUS features were present, the best sensitivity of 100% for malignancy identification was obtained with the specificity of 66.7% and the AUC of 0.833. When at least two of the three discriminant CEUS features were present, the best area under the receiver operating characteristic curve (AUC) of 0.924 for malignancy identification was obtained. The combination of at least two discriminant CEUS features showed much better diagnostic performance than the optimal combination of ultrasound features in terms of AUC (0.924 vs 0.608, p < 0.0001), sensitivity (94.0% vs 42.0%, p < 0.0001), and specificity (90.7% vs 79.6%, p = 0.210) for the indeterminate tumors. CONCLUSION: The combination CEUS features of enlargement of enhancement area, infiltrative enhancement boundary and intratumoral arrival time difference are valuable to improve the discriminating performance for indeterminate soft-tissue tumors on conventional ultrasound. ADVANCES IN KNOWLEDGE: The combination of peritumoral and arrival-time CEUS features can improve the discriminating performance for indeterminate soft-tissue tumors on conventional ultrasound.

Comprehensive Identification and Expression Profiling of the VQ Motif-Containing Gene Family in Brassica juncea.

Valine-glutamine (VQ) motif-containing proteins are a class of highly conserved transcriptional regulators in plants and play key roles in plant growth, development, and response to various stresses. However, the VQ family genes in mustard have not yet been comprehensively identified and analyzed. In this study, a total of 120 VQ family genes (BjuVQ1 to BjuVQ120), which were unevenly distributed on 18 chromosomes (AA_Chr01 to BB_Chr08), were characterized in mustard. A phylogenetic tree analysis revealed that the BjuVQ proteins were clustered into nine distinct groups (groups I to IX), and members in the same group shared a highly conserved motif composition. A gene structure analysis suggested that most BjuVQ genes were intronless. A gene duplication analysis revealed that 254 pairs of BjuVQ genes were segmentally duplicated and one pair was tandemly duplicated. Expression profiles obtained from RNA-seq data demonstrated that most BjuVQ genes have different gene expression profiles in different organs, including leaf, stem, root, flower bud, pod, and seed. In addition, over half of the BjuVQ genes were differentially expressed at some time points under low temperature treatment. The qRT-PCR data revealed that BjuVQ23, BjuVQ55, BjuVQ57, BjuVQ67, BjuVQ100, and BjuVQ117 were upregulated in response to cold stress. Taken together, our study provides new insights into the roles of different BjuVQ genes in mustard and their possible roles in growth and development, as well as in response to cold stress.

Chordin-Like 2: A Possible Therapeutic Target for Gastric Cancer by Affecting Cell Cycle and Proliferation.

Purpose: This study aimed to examine the role of chordin-like 2 (CHRDL2) in gastric cancer. Methods: The Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets were screened and the differentially expressed gene CHRDL2 was identified. The CHRDL2 expression was examined in the Human Protein Atlas and TCGA. Clinical data on gastric cancer were evaluated for their association with CHRDL2 by using TCGA and KM-plotter databases. The possible relationship amongst CHRDL2, immune cells, and related genes was investigated via the TIMER database. Enrichment analysis was performed using GO and KEGG pathways to explore the mechanisms. Results: Screening of databases revealed that CHRDL2 was a differentially expressed gene. An increase in cytoplasmic CHRDL2 expression was found in cancer tissues compared with the surrounding normal tissues. The data, together with those from TCGA and the KM-plotter databases, showed that patients with gastric cancer with high level of CHRDL2 have worse prognosis than those with low expression. A strong correlation was found between CHRDL2 expression and T stage, race, pathological grade, and pathological type according to clinical data analysis. CHRDL2 expression is linked to immune infiltration, as shown by the TIMER database. The data suggested that CHRDL2 plays a pivotal role in the tumor microenvironment of gastric cancer and might help tumor cells evade the immune system. Gene set enrichment analysis showed that CHRDL2 is involved in the chemokine signaling route, the intestinal immune network, the MAPK pathway, cell cycle, and the PI3K-Akt signaling system that are associated with the pathological processes of gastric cancer. Conclusion: Patients with gastric cancer with decreased CHRDL2 levels have dramatically improved OS, PFS, and PPS. CHRDL2 plays a pivotal role in enabling tumor cell immune evasion in tumor microenvironment, suggesting a function of this gene in the development of gastric cancer and its immune infiltration. Interfering with CHRDL2 may slow down the development of this malignancy by affecting cell cycle and apoptosis pathways.

Analysis of gamma spectra from burnup measurement in HTR-10.

HTR-10, the 10 MW pebble-bed High Temperature Gas-cooled Reactor-Test Module designed by Tsinghua University, achieved its first criticality in 2000. One of the unique features of HTR-10 is the continuous fuel feeding achieved by its fuel cycle system, in which the fuel sphere is allowed to pass through the core several times before discharged out. During the fuel circulation, the on-line burnup measurement system is used to ensure fuel credit. Up to now, after nearly 21 years of operation, huge data including gamma spectra have been collected by this on-line burnup measurement system. In this paper, the gamma spectra data collected from Nov. 2005 to Mar. 2006 are analyzed to identify the radionuclides left in the irradiated fuel sphere after a long decay. The analysis includes energy identification, decay scheme confirmation, activity estimation and so on. This work shows that radionuclides and corresponding activities are preliminarily identified, which lays a base for R&D of new burnup measurement apparatus and the profiling of fuel irradiation history. That would help to increase accuracy for the nuclear material accounting and to improve the operation strategy of pebble bed high-temperature gas-cooled reactors.

Abnormal Anatomical and Functional Connectivity of the Thalamo-sensorimotor Circuit in Chronic Low Back Pain: Resting-state Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging Study.

Thalamocortical dysfunction is thought to underlie the pathophysiology of chronic pain revealed by electroencephalographic studies. The thalamus serves as a primary relay center to transmit sensory information and motor impulses via dense connections with the somatosensory and motor cortex. In this study, diffusion tensor imaging (DTI) (probabilistic tractography) and resting-state functional magnetic resonance imaging (functional connectivity) were used to characterize the anatomical and functional integrity of the thalamo-sensorimotor pathway in chronic low back pain (cLBP). Fifty-four patients with cLBP and 54 healthy controls were included. The results suggested significantly increased anatomical connectivity of the left thalamo-motor pathway characterized by probabilistic tractography in patients with cLBP. Moreover, there was significantly altered resting-state functional connectivity (rsFC) of bilateral thalamo-motor/somatosensory pathways in patients with cLBP as compared to healthy controls. We also detected a significant correlation between pain intensity during the MRI scan and rsFC of the right thalamo-somatosensory pathway in cLBP. Our findings highlight the involvement of the thalamo-sensorimotor circuit in the pathophysiology of cLBP.

Altered effective connectivity within the cingulo-frontal-parietal cognitive attention networks in chronic low back pain: a dynamic causal modeling study.

Dysfunction of the cingulo-frontal-parietal (CFP) cognitive attention network has been associated with the pathophysiology of chronic low back pain (cLBP). However, the direction of information processing within this network remains largely unknown. We aimed to study the effective connectivity among the CFP regions in 36 cLBP patients and 36 healthy controls by dynamic causal modeling (DCM). Both the resting-state and task-related (Multi-Source Interference Task, MSIT) functional magnetic resonance imaging (fMRI) data were collected and analyzed. The relationship between the effective connectivity of the CFP regions and clinical measures was also examined. Our results suggested that cLBP had significantly altered resting-state effective connectivity of the prefrontal cortex (PFC)-to-mid-cingulate cortex (MCC) (increased) and MCC-to-left superior parietal cortex (LPC) (decreased) pathways as compared with healthy controls. MSIT-related DCM suggested that the interference task could significantly increase the effective connectivity of the right superior parietal cortex (RPC)-to-PFC and RPC-to-MCC pathways in cLBP than that in healthy controls. The control task could significantly decrease the effective connectivity of the MCC-to-LPC and MCC-to-RPC pathways in cLBP than that in healthy controls. The endogenous connectivity of the PFC-to-RPC pathway in cLBP was significantly lower than that in healthy controls. No significant correlations were found between the effective connectivity within CFP networks and pain/depression scores in patients with cLBP. In summary, our findings suggested altered effective connectivity in multiple pathways within the CFP network in both resting-state and performing attention-demanding tasks in patients with cLBP, which extends our understanding of attention dysfunction in patients with cLBP.

Detection of the 23-bp nucleotide sequence mutation in retinoid acid receptor related orphan receptor alpha (RORA) gene and its effect on sheep litter size.

Retinoid acid receptor related orphan receptor alpha (RORA) transcribes steroid-related genes to regulate estrogen synthesis. As an important reproductive trait, litter size relates to estrogen synthesis. Therefore, it is important to investigate the association between RORA gene and sheep litter size. In this study, one 23-bp nucleotide sequence mutation was identified in intron 1 of RORA gene in 532 female Australian White Sheep. Moreover, the polymorphic information content (PIC) values of this locus was 0.219. The litter size of ID genotype was significantly better than II genotype and DD genotype in the second born litter size (p < 0.05). This loci was related to third born litter size and the ID is the dominant genotype (p < 0.05). The association between combined genotypes and average litter size showed that sheep with heterozygote (ID) genotypes had larger lamb than homozygous (DD and II) genotypes. To sum, this study provided theoretical references for the comprehensively research of the function of RORA gene and the breeding of Australian White Sheep. The 23-bp indel variants could be considered as molecular markers for the second and third born litter size of sheep for MAS breeding.

Indel mutations of sheep PLAG1 gene and their associations with growth traits.

Pleiomorphic adenoma gene 1 (PLAG1) is mainly expressed in embryonic development, and it is reported to take an effect on the growth performance of mice, cattle, pigs, and sheep. To explore how conservative the PLAG1 is in different sheep breeds, the effects of the two indel variants on the growth traits of the Chinese Luxi blackhead (LXBH) sheep were firstly detected. The P2-del 30 bp and P4-del 45 bp indel loci of the sheep PLAG1 gene were significantly related to 15 growth traits (P < 0.05). Genotype ID and genotype II were dominant for the P2-del 30 bp and P4-del 45 bp loci, respectively. The above findings indicated that the two indel mutations in the ovine PLAG1 gene were suggested to become the molecular markers for the selection of economic traits in sheep.