Clinical significance of serum oxidative stress and serum uric acid levels before surgery for hepatitis B-related liver cancer.

BACKGROUND: The incidence and mortality of liver cancer are among the highest of all malignant tumors in China. The high recurrence rate after conventional hepatectomy is worrying. There is a lack of effective prognostic indicators for liver cancer. AIM: To explore the clinical significance of preoperative serum oxidative stress and serum uric acid (UA) levels in hepatitis B-related liver cancer. METHODS: The medical records of 110 hepatitis B-related liver cancer patients who underwent hepatectomy in Gansu Provincial Hospital were retrospectively analyzed. Recurrence in patients within 3 years after surgery was determined. The logistic regression model and Pearson or Spearman correlation were used to analyze the correlation between oxidative stress level and UA, and the recurrence of hepatitis B-related liver cancer. RESULTS: Compared with the non-recurrence group, the levels of superoxide dismutase (SOD) and glutathione (GSH) in the recurrence group were lower and the levels of malondialdehyde (MDA) and UA were higher (all P < 0.05). UA, SOD, MDA, and GSH were risk factors for postoperative recurrence in hepatitis B-related liver cancer patients (P < 0.05). UA was positively correlated with MDA (r = 0.395, P < 0.001) and negatively correlated with GSH (r = -0.204, P = 0.032). The area under the receiver operating characteristic curve (AUC) of SOD, MDA, GSH, and UA in predicting the prognosis was 0.276, 0.910, 0.199, and 0.784, respectively (all P < 0.001). CONCLUSION: The preoperative serum SOD, GSH, MDA, and UA levels had significant predictive effects on postoperative recurrence of hepatitis B-related liver cancer.

Distinct brain state dynamics of native and second language processing during narrative listening in late bilinguals.

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.

Detecting the visual word form area in a bilingual brain.

Utilizing a millimeter-scale fMRI technique and individual-based analysis, Zhan and colleagues drew a new cortical map of the visual word form area (VWFA) and examined how it processes diverse languages among different bilinguals. This research advances the current understanding of cortical language organization in the bilingual brain.

Functional preference of the left inferior parietal lobule to second language reading.

Additional neural substance for reading in a second language has been reported by prior studies. However, to date, there has been little investigation into whether and how the brain's adaptation to a second language is induced by specific linguistic tasks or is a general effect during reading in a new language. To address this issue, our study investigated Chinese children learning English as a second language by combining cross-sectional and longitudinal Functional Magnetic Resonance Imaging (fMRI) studies. We compared brain activation across four reading tasks, orthographic tasks and phonological tasks in Chinese (the first language, L1) and English (the second language, L2). By comparing the activation pattern across languages, we observed greater activation in the left inferior parietal lobule (LIPL) in English compared to Chinese, suggesting a functional preference of the LIPL to L2. In addition, greater correlation between LIPL-related FC and L2 was mainly observed in the phonological task, indicating that LIPL could be associated with phonological processing. Moreover, a proportion of the children were enrolled in an 8-week phonological-based reading-training program. We observed significant functional plasticity of the LIPL elicited by this training program only in the English phonological task and not in the orthographic task, further substantiating that the additional requirements of the LIPL in L2 are mainly associated with phonological processing. The findings provide new insights into understanding the functional contribution of the LIPL to reading in a second language.

Universality and language specificity of brain reading networks: A developmental perspective.

The development of reading networks across different languages and cultures provides an important window to address gene-culture interactions in brain functionality development. Previous meta-analyses have explored the neural correlates of reading in different languages with diverse orthographic transparencies. However, it remains unknown whether the neural topographic relationship of different languages varies when taking development into account. To address this issue, we conducted meta-analyses of neuroimaging studies with approaches of activation likelihood estimation and seed-based effect size mapping and focused on two highly contrasting languages, Chinese and English. The meta-analyses covered 61 studies of Chinese reading and 64 studies of English reading by native speakers. The brain reading networks of child and adult readers were further separately analyzed and compared to explore the developmental effects. The results revealed that the commonalities and differences in reading networks for Chinese and English were inconsistent between children and adults. In addition, the reading networks converged with development, and the effects of writing systems on brain function organizations were more salient in the initial stages of reading. An interesting finding was that the left inferior parietal lobule demonstrated increased effect sizes in adults compared with children in both Chinese and English reading, indicating a common developmental feature of reading mechanisms across the two languages. These findings provide new insights into the functional evolution and cultural modulation of brain reading networks. RESEARCH HIGHLIGHTS: Meta-analyses with approaches of activation likelihood estimation and seed-based effect size mapping were performed to evaluate the developmental characteristics of brain reading networks. The engagement of universal and language-specific reading networks was different between children and adults, and the reading networks converged with increased reading experience. Overall the middle/inferior occipital and inferior/middle frontal gyrus were specific to Chinese and the middle temporal, right inferior frontal gyrus were specific to English. The left inferior parietal lobule was engaged more in adults than children in Chinese and English reading, demonstrating a common developmental feature of reading mechanisms.

Brain fingerprints along the language hierarchy.

Recent studies have shown that the brain functional connectome constitutes a unique fingerprint that allows the identification of individuals from a group. However, what information encoded in the brain that makes us unique remains elusive. Here, we addressed this issue by examining how individual identifiability changed along the language hierarchy. Subjects underwent fMRI scanning during rest and when listening to short stories played backward, scrambled at the sentence level, and played forward. Identification for individuals was performed between two scan sessions for each task as well as between the rest and task sessions. We found that individual identifiability tends to increase along the language hierarchy: the more complex the task is, the better subjects can be distinguished from each other based on their whole-brain functional connectivity profiles. A similar principle is found at the functional network level: compared to the low-order network (the auditory network), the high-order network is more individualized (the frontoparietal network). Moreover, in both cases, the increase in individual identifiability is accompanied by the increase in inter-subject variability of functional connectivities. These findings advance the understanding of the source of brain individualization and have potential implications for developing robust connectivity-based biomarkers.

Nonverbal cognitive control training increases the efficiency of frontal-subcortical collaboration for bilingual language control.

Domain-general cognitive control is closely related to language control during bilingual language production. Previous neural imaging studies have revealed a highly overlapped but rewired brain network for language control and nonverbal cognitive control. In the present study, we examined this issue from a training perspective. Two groups of participants performed the language switching task at pre-and post-tests during functional magnetic resonance imaging (fMRI) scanning. After the pre-test, the experimental group received 8-day training in a non-verbal switching task, while the control group performed an unrelated color judgement task. We found that only the experimental group but not the control group showed decreased strength of connectivity from the ventral lateral frontal cortex to the left caudate nucleus and from the medial surface of the frontal lobe to the left thalamus. These results indicate an increased efficiency after nonverbal training for the frontal cortex to implement domain-general suppression and monitoring in a domain-specific conflict context during bilingual language and lexical selections. This study is the first to investigate the transfer effects of nonverbal cognitive control on the brain network of bilingual language control and shed light on the mechanisms of how domain-general cognitive control may underpin bilingual language control.

Functional mapping and cooperation between the cerebellum and cerebrum during word reading.

Multiple areas in the cerebellum have been reported to be engaged in reading. However, how these regions cooperate with the reading-related areas in the cerebrum remains unclear. Here, brain images of fifty-two adults were acquired via functional magnetic resonance imaging. By comparing the cerebellar activation across three localization tasks targeting orthographic, phonological, and semantic processing, we first identified three different reading-related areas in the cerebellum, biased toward orthography, phonology, and semantics, respectively. Then, functional connectivity (FC) analyses demonstrated that the mean FC between functionally corresponding areas across the cerebrum and cerebellum was greater than that between noncorresponding areas during silent word reading. FC patterns of functionally corresponding areas could significantly predict reading speed, with the FC driven from orthographic and semantic areas contributing the most. Effective FC analyses further showed that orthographic and semantic areas in the cerebellum had selective and direct connectivity to areas in the cerebrum with similar functional specificity. These results suggest that reading-related areas vary in their functions to reading, and cooperation between areas with corresponding functions was greater than that between noncorresponding areas. These findings emphasize the importance of functional cooperation between the cerebrum and cerebellum during reading from a new perspective.

The "two-brain" approach reveals the active role of task-deactivated default mode network in speech comprehension.

Exhibiting deactivation and anticorrelation with task-positive networks, the default mode network (DMN) has been traditionally thought to be suppressed to support externally oriented cognitive processes during spoken language comprehension. In contrast, recent studies examining listener-listener intersubject correlation (ISC) have proposed an active role of DMN in language comprehension. How can we reconcile those seemingly conflicting results? This study adopted a "two-brain" paradigm and combined "within-brain" and "across-brain" analyses to address this issue. We found, despite being deactivated and anticorrelated with the language network (LN) and executive control network (ECN), both the anterior and posterior DMN in the listeners' brains were temporally coupled with the homologous networks in the speaker's brain. Interestingly, the listener-speaker neural couplings persisted even after controlling for listener-listener ISC. Moreover, the coupling strength of posterior DMN positively correlated with the listeners' speech comprehension. Further dynamic causal modeling showed that the LN and ECN, the anterior DMN, and the posterior DMN occupied the bottom, intermediate, and top layers of a hierarchical system, respectively. We suggest the DMN may primarily serve as an internal module that cooperates with the externally oriented modules, potentially supporting the transformation of external acoustic signals into internal mental representations during successful language comprehension.

The Exosomes Containing LINC00461 Originated from Multiple Myeloma Inhibit the Osteoblast Differentiation of Bone Mesenchymal Stem Cells via Sponging miR-324-3p.

Multiple myeloma is one of the hematological malignancies and inhibited osteoblast differentiation of bone marrow mesenchymal stem cells (BM-MSCs) which has been proved as a major complication of the patients with multiple myeloma. However, the pathomechanism of symptom remains unclear. Besides, several studies have indicated that LINC00461 plays an important role in the progression of multiple tumors. Hence, this study attempted to reveal the role of LINC00461 in the osteoblast differentiation of MSCs. In this study, the expression level of LINC00461 in the exosomes of multiple myeloma cells was measured, and BM-MSCs were cultured with the exosomes to observe the change of cellular phenotype. Moreover, downstream target of LINC00461 was searched and verified with dual-luciferase reporter assay, and the activation of the Wnt/ß-catenin pathway was also observed by Western blot. The results showed that the isolated BMSCs exhibited special biomarkers of MSCs. LINC00461 was significantly upregulated in the exosomes originated multiple myeloma cells, and increased LINC00461 significantly impeded the osteoblast differentiation of MSCs. Moreover, LINC00461 could significantly suppress the activation of the Wnt/ß-catenin pathway in MSCs. In conclusion, this study suggested that LINC00461 in exosomes of multiple myeloma could reduce the activity of the Wnt/ß-catenin pathway to inhibit the osteoblast differentiation of BM-MSCs via targeting miR-324-3p.

The cerebellum and cognition: further evidence for its role in language control.

The cognitive function of the human cerebellum could be characterized as enigmatic. However, researchers have attempted to detail the comprehensive role of the cerebellum in several cognitive processes in recent years. Here, using functional magnetic resonance imaging (fMRI) and transcranial direct current stimulation (tDCS), we revealed different functions of bilateral cerebellar lobules in bilingual language production. Specifically, brain activation showed the bilateral posterolateral cerebellum was associated with bilingual language control, and an effective connectivity analysis built brain networks for the interaction between the cerebellum and the cerebral cortex. Furthermore, anodal tDCS over the right cerebellum significantly optimizes language control performance in bilinguals. Together, these results reveal a precise asymmetrical functional distribution of the cerebellum in bilingual language production, suggesting that the right cerebellum is more involved in language control. In contrast, its left counterpart undertakes a computational role in cognitive control function by connecting with more prefrontal, parietal, subcortical brain areas.

"Antagonistic" cooperation of control regions in bilingual language production: An effective connectivity study.

The dorso-lateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) are two main regions that support bilingual language control during language production. Previous studies have suggested that the regions work together in language control processes. However, how they cooperate with each other during bilingual language production is far from clear. We addressed this issue by recruiting bimodal bilingual participants whose two languages could be separated at a neural level. Functional magnetic resonance imaging scans were acquired from the participants as they performed a dual-language production task and a spoken-production task. Dynamic causal modelling (DCM) was used to analyse the effective connectivity between the ACC and the DLPFC as well as the causal relationships among the control regions and language regions. We found that the ACC had positive effective connectivity to the DLPFC, left precentral gyrus and left superior temporal gyrus, while the DLPFC had negative effective connectivity to the other three regions. A similar pattern of effective connectivity between the control regions and language regions was also found in the spoken-production task. These results showed that the ACC may promote the production of the target language, while the DLPFC has an inhibitory effect in language production. The findings suggest an antagonistic relationship between the DLPFC and ACC that cooperatively ensures fluent language production in bilinguals.

The selective contributions of right cerebellar lobules to reading.

The engagement of the cerebellum during reading tasks is not unprecedented. However, it is still unclear which regions in the cerebellum are specifically involved in reading and how the cerebellum processes different languages. With functional magnetic resonance imaging, we compared the cerebellar neural activity in Chinese child learners of English between reading and non-reading tasks to identify functionally specialized areas for reading, and between Chinese characters and English words in a passive viewing paradigm to detect regions sensitive to different scripts. Two posterior subregions of right lobule VI, as well as right lobule VIIIA, demonstrated greater activation to viewing Chinese characters and English words compared to the non-reading tasks. However, we did not find any cerebellar regions that were differentially responsive to Chinese versus English print. Instead, we observed that functional connectivity between the two above-mentioned cerebellar regions (lobules VI and VIIIA) and the left inferior parietal lobule was significantly greater in English reading compared to Chinese reading. Overall, these results indicate that the posterior parts of right lobule VI and the right lobule VIIIA could be reading-specific regions, and deepen our understanding of how the cerebellum contributes to reading.

Left and Right Arcuate Fasciculi Are Uniquely Related to Word Reading Skills in Chinese-English Bilingual Children.

Whether reading in different writing systems recruits language-unique or language-universal neural processes is a long-standing debate. Many studies have shown the left arcuate fasciculus (AF) to be involved in phonological and reading processes. In contrast, little is known about the role of the right AF in reading, but some have suggested that it may play a role in visual spatial aspects of reading or the prosodic components of language. The right AF may be more important for reading in Chinese due to its logographic and tonal properties, but this hypothesis has yet to be tested. We recruited a group of Chinese-English bilingual children (8.2 to 12.0 years old) to explore the common and unique relation of reading skill in English and Chinese to fractional anisotropy (FA) in the bilateral AF. We found that both English and Chinese reading skills were positively correlated with FA in the rostral part of the left AF-direct segment. Additionally, English reading skill was positively correlated with FA in the caudal part of the left AF-direct segment, which was also positively correlated with phonological awareness. In contrast, Chinese reading skill was positively correlated with FA in certain segments of the right AF, which was positively correlated with visual spatial ability, but not tone discrimination ability. Our results suggest that there are language universal substrates of reading across languages, but that certain left AF nodes support phonological mechanisms important for reading in English, whereas certain right AF nodes support visual spatial mechanisms important for reading in Chinese.

Large-scale network topology reveals brain functional abnormality in Chinese dyslexic children.

It has been revealed that dyslexic children learning alphabetic languages are characterized by aberrant topological organization of brain networks. However, little is known about the functional organization and the reconfiguration pattern of brain networks in Chinese dyslexic children. Using graph theoretical analysis and functional magnetic resonance images (fMRI), we examined this issue specifically from the perspective of functional integration and segregation. We first compared large-scale topological organizations between dyslexic children and typically developing children during a Chinese phonological rhyming task, and found that dyslexic children showed increased local efficiency and clustering coefficient compared with typically developing children, which were negatively correlated with task performance. Furthermore, dyslexic children and typically developing children could be accurately distinguished at the individual-subject level based on the nodal local efficiency or clustering coefficient. Second, we studied the group difference of network reconfiguration and found that dyslexic children showed more difficulty when shifting from the resting state to the phonological task. Our results suggest an over-segregated brain functional organization and deficits in brain network reconfiguration in Chinese dyslexic children, which helps to advance our knowledge on the neural mechanisms underlying dyslexia.

The cortical organization of writing sequence: evidence from observing Chinese characters in motion.

Writing sequences play an important role in handwriting of Chinese characters. However, little is known regarding the integral brain patterns and network mechanisms of processing Chinese character writing sequences. The present study decoded brain patterns during observing Chinese characters in motion by using multi-voxel pattern analysis, meta-analytic decoding analysis, and extended unified structural equation model. We found that perception of Chinese character writing sequence recruited brain regions not only for general motor schema processing, i.e., the right inferior frontal gyrus, shifting, and inhibition functions, i.e., the right postcentral gyrus and bilateral pre-SMA/dACC, but also for sensorimotor functions specific for writing sequences. More importantly, these brain regions formed a cooperatively top-down brain network where information was transmitted from brain regions for general motor schema processing to those specific for writing sequences. These findings not only shed light on the neural mechanisms of Chinese character writing sequences, but also extend the hierarchical control model on motor schema processing.

Reduced listener-speaker neural coupling underlies speech understanding difficulty in older adults.

An increasing number of studies have highlighted the importance of listener-speaker neural coupling in successful verbal communication. Whether the brain-to-brain coupling changes with healthy aging and the possible role of this change in the speech comprehension of older adults remain unexplored. In this study, we scanned with fMRI a young and an older speaker telling real-life stories and then played the audio recordings to a group of young (N = 28, aged 19-27 year) and a group of older adults during scanning (N = 27, aged 53-75 year), respectively. The older listeners understood the speech less well than did the young listeners, and the age of the older listeners was negatively correlated with their level of speech understanding. Compared to the young listener-speaker dyads, the older dyads exhibited reduced neural couplings in both linguistic and extra-linguistic areas. Moreover, within the older group, the listener's age was negatively correlated with the overall strength of interbrain coupling, which in turn was associated with reduced speech understanding. These results reveal the deficits of older adults in achieving neural alignment with other brains, which may underlie the age-related decline in speech understanding.

Failure of resting-state frontal-occipital connectivity in linking visual perception with reading fluency in Chinese children with developmental dyslexia.

It is widely accepted that impairment in visual perception impedes children's reading development, and further studies have demonstrated significant enhancement in reading fluency after visual perceptual training. However, the mechanism of the neural linkage between visual perception and reading is unclear. The purpose of this study was to examine the intrinsic functional relationship between visual perception (indexed by the texture discrimination task,TDT) and reading ability (character reading and reading fluency) in Chinese children with developmental dyslexia (DD) and those with typical development (TD). The resting-state functional connectivity (RSFC) between the primary visual cortex (V1, BA17) and the entire brain was analyzed. In addition, how RSFC maps are associated with TDT performance and reading ability in the DD and TD groups was examined. The results demonstrated that the strength of the RSFC between V1 and the left middle frontal gyrus (LMFG, BA9/BA46) was significantly correlated with both the threshold (SOA) of the TDT and reading fluency in TD children but not in DD children. Moreover, LMFG-V1 resting-state connectivity played a mediating role in the association of visual texture discrimination and reading fluency, but not in character reading, in TD children. In contrast, this mediation was absent in DD children, albeit their strengths of RSFC between V1 and the left middle frontal gyrus (LMFG) were comparable to those for the TD group. These findings indicate that typically developing children use the linkage of the RSFC between the V1 and LMFG for visual perception skills, which in turn promote fluent reading; in contrast, children with dyslexia, who had higher TDT thresholds than TD children, could not take advantage of their frontal-occipital connectivity to improve reading fluency abilities. These findings suggest that visual perception plays an important role in reading skills and that children with developmental dyslexia lack the ability to use their frontal-occipital connectivity to link visual perception with reading fluency.

Patterns and networks of language control in bilingual language production.

Many studies have examined the cognitive and neural mechanisms of bilingual language control, but few of them have captured the pattern information of brain activation. However, language control is a functional combination of both cognitive control and language production which demonstrates distinct patterns of neural representations under different language contexts. The first aim of the present study was to explore the brain activation patterns of language control using multivoxel pattern analysis (MVPA). During the experiment, Chinese-English bilinguals were instructed to name pictures in either Chinese or English according to a visually presented cue while being scanned with functional magnetic resonance imaging (fMRI). We found that patterns of neural activity in frontal brain regions including the left dorsolateral prefrontal cortex, left inferior frontal gyrus, left supplementary motor area, anterior cingulate cortex, bilateral precentral gyri, and the left cerebellum reliably discriminated between switch and non-switch conditions. We then modeled causal interactions between these regions by applying effective connectivity analyses based on an extended unified structure equation model (euSEM). The results showed that frontal and fronto-cerebellar connectivity were key components of the language control network. These findings further reveal the engagement of the cognitive control network in bilingual language production.

A universal reading network and its modulation by writing system and reading ability in French and Chinese children.

Are the brain mechanisms of reading acquisition similar across writing systems? And do similar brain anomalies underlie reading difficulties in alphabetic and ideographic reading systems? In a cross-cultural paradigm, we measured the fMRI responses to words, faces, and houses in 96 Chinese and French 10-year-old children, half of whom were struggling with reading. We observed a reading circuit which was strikingly similar across languages and consisting of the left fusiform gyrus, superior temporal gyrus/sulcus, precentral and middle frontal gyri. Activations in some of these areas were modulated either by language or by reading ability, but without interaction between those factors. In various regions previously associated with dyslexia, reading difficulty affected activation similarly in Chinese and French readers, including the middle frontal gyrus, a region previously described as specifically altered in Chinese. Our analyses reveal a large degree of cross-cultural invariance in the neural correlates of reading acquisition and reading impairment.