Distinctive and complementary roles of default mode network subsystems in semantic cognition.

The default mode network (DMN) typically deactivates to external tasks, yet supports semantic cognition. It comprises medial temporal (MT), core, and fronto-temporal (FT) subsystems, but its functional organisation is unclear: the requirement for perceptual coupling versus decoupling, input modality (visual/verbal), type of information (social/spatial) and control demands all potentially affect its recruitment. We examined the effect of these factors on activation and deactivation of DMN subsystems during semantic cognition, across four task-based human functional magnetic resonance imaging (fMRI) datasets, and localised these responses in whole-brain state space defined by gradients of intrinsic connectivity. FT showed activation consistent with a central role across domains, tasks and modalities, although it was most responsive to abstract, verbal tasks; this subsystem uniquely showed more 'tuned' states characterised by increases in both activation and deactivation when semantic retrieval demands were higher. MT also activated to both perceptually-coupled (scenes) and decoupled (autobiographical memory) tasks, and showed stronger responses to picture associations, consistent with a role in scene construction. Core DMN consistently showed deactivation, especially to externally-oriented tasks. These diverse contributions of DMN subsystems to semantic cognition were related to their location on intrinsic connectivity gradients: activation was closer to sensory-motor cortex than deactivation, particularly for FT and MT, while activation for core DMN was distant from both visual cortex and cognitive control. These results reveal distinctive yet complementary DMN responses: MT and FT support different memory-based representations that are accessed externally and internally, while deactivation in core DMN is associated with demanding, external semantic tasks.Significance Statement We delineate the functional organisation of DMN in semantic cognition, examining effects of perceptual coupling versus decoupling, input modality (visual/verbal), domain (social/spatial) and control demands across DMN subsystems in four fMRI datasets. These subsystems played complementary roles in semantic cognition related to their locations on gradients of intrinsic connectivity. Medial temporal and frontotemporal subsystems supported visuospatial and abstract conceptual information respectively, across both internally and externally-focussed tasks, while deactivation in core DMN was associated with focussed and externally-oriented semantic states. We conclude that both content and process are relevant to the functional architecture of DMN in semantic cognition.

Enhanced ε­poly­L­lysine production in Streptomyces species by combining interspecific hybridization with multiple antibiotic resistance.

To improve the ε-PL production in wild-type strains of Streptomyces. albulus, Streptomyces. noursei, Streptomyces. rochei and Streptomyces. yunnanensis, the interspecific hybridization based on protoplast fusion was first performed. Two-species hybridizations failed to obtain hybrids with significant increase in ε-PL production, but four-species hybridizations succeed in acquiring many high-yield hybrids. 16S rDNA homology alignment and RAPD confirmed that the hybrid HX17 was restructured by integrating gene fragments from S. albulus and S. rochei with S. noursei as the carrier. S. noursei HX17 was subsequently suffered from mutagenesis and genome shuffling combining with multiple antibiotic resistance, and a mutant S. noursei GX6 was obtained with ε-PL yield of 2.23 g/L in shake-flask fermentation. In fed-batch fermentation, the ε-PL production of GX6 reached 47.2 g/L, which was increased by 95.6% to 136.8% over the wild parents. Ribosomal genes associated with antibiotics were sequenced and majority of mutant strains had mutations at different sites, indicating that the increase of antibiotic resistance was strongly associated with them. This research proved that combining interspecific hybridization with multiple antibiotic resistance was as an effective approach to rapidly improve the ε-PL production in Streptomyces species.

Two cases of driver death caused by airbag rupture.

OBJECTIVE: This article reports two accidents caused by defective Takata airbags ruptured, which led to the deaths of the drivers. This is the first public report on the deaths caused by Takata airbags in China. METHODS: Determine the relationship between the driver death and airbag rupture through autopsy indings and vehicle inspection. RESULTS: Due to defects in the design of Takata's inflator, moist air was permitted to slowly enter the inflator, resulting the PSAN slowly degraded physically. The damaged propellant burned more rapidly than intended and overpressurized the inflator's steel housing, causing fragmentation and flying debris at high speed, killing or injuring vehicle occupants. CONCLUSIONS: To date, there are still tens of millions of defective Takata airbags that have not been recalled for repair, posing safety risks. This article suggests taking preventive measures to avoid the occurrence of similar accidents.

ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.

Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both in vitro and in vivo. ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.

Gum Arabic-Derived Hydroxyproline-Rich Peptides Stimulate Intestinal Nonheme Iron Absorption via HIF2α-Dependent Upregulation of Iron Transport Proteins.

The stimulation of host iron absorption is a promising antianemia strategy adjunctive/alternative to iron intervention. Here, gum arabic (GA) containing 3.14 ± 0.56% hydroxyproline-rich protein with repetitive X-(Pro/Hyp)n motifs was found to increase iron reduction, uptake, and transport to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin, and hephaestin to inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) and to stabilize HIF2α in polarized Caco-2 cell monolayers in a dose-dependent manner, and this was dependent on its protein fraction, rather than the polysaccharide fraction. Three abundant GA-derived hydroxyproline-containing dipeptides of Hyp-Hyp, Pro-Hyp, and Ser-Hyp were detected by liquid chromatography-mass spectrometry in the lysates of polarized Caco-2 cell monolayers at the maximum levels of  0.167 ± 0.021, 0.134 ± 0.017, and 0.089 ± 0.015 µg/mg of protein, respectively, and showed desirable docking affinity energy values of -7.53, - 7.91, and -7.39 kcal/mol, respectively, against human PHD3. GA-derived peptides also acutely increased duodenal HIF2α stability and Dcytb, DMT1, ferroportin, and hephaestin transcription in rats (P < 0.05). Overall, GA-derived hydroxyproline-rich peptides stimulated intestinal iron absorption via PHD inhibition, HIF2α stabilization, and subsequent upregulation of iron transport proteins.

Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo.

Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the H2O2-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1ß-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.

Experience sampling reveals the role that covert goal states play in task-relevant behavior.

Cognitive neuroscience has gained insight into covert states using experience sampling. Traditionally, this approach has focused on off-task states. However, task-relevant states are also maintained via covert processes. Our study examined whether experience sampling can also provide insights into covert goal-relevant states that support task performance. To address this question, we developed a neural state space, using dimensions of brain function variation, that allows neural correlates of overt and covert states to be examined in a common analytic space. We use this to describe brain activity during task performance, its relation to covert states identified via experience sampling, and links between individual variation in overt and covert states and task performance. Our study established deliberate task focus was linked to faster target detection, and brain states underlying this experience-and target detection-were associated with activity patterns emphasizing the fronto-parietal network. In contrast, brain states underlying off-task experiences-and vigilance periods-were linked to activity patterns emphasizing the default mode network. Our study shows experience sampling can not only describe covert states that are unrelated to the task at hand, but can also be used to highlight the role fronto-parietal regions play in the maintenance of covert task-relevant states.

Comparative Proteomic Analysis of Irradiation-Induced Radioresistant Breast Cancer Cells Using Label-Free Quantitation.

BACKGROUND: Breast cancer poses severe threats to human health as radioresistance becomes increasingly prevalent. The mechanisms of radioresistance are hard to expound completely. This study aims to explore proteomic changes of radioresistance, which will help elucidate the potential mechanisms responsible for breast cancer radioresistance and explore potential therapeutic targets. METHODS: A radioresistant breast cancer cell line was established by repeated irradiation. Liquid Chromatograph Mass Spectrometer (LC-MS) was used to quantify protein expression. Proteomic changes associated with radioresistance were evaluated by proteomic analysis. Further, cell radioresistance and several identified proteins were verified in in vitro experiments. RESULTS: In the study, more than 3000 proteins were detected, 243 of which were identified as up-regulated proteins and another 633 as down-regulated proteins. Gene Ontology (GO) enrichment analysis indicated that these proteins were mainly expressed in the lysosome and ribosome, associated with coenzyme binding and the structural constituent of the ribosome, involved in mitotic cytokinesis and ribonucleoprotein complex biogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many biological processes were extensively altered, particularly spliceosome and thermogenesis. It is worth noting that the functions and pathways related to ribosomes were significantly enriched, therefore ribosomal proteins (RPL6 and RPS13) were identified through western blot and highly expressed in relatively radiosensitive cells. Additionally, several identified proteins, including S100A4, RanBP9, and ISG15, were also verified to be differentially expressed in different radiosensitive cells. CONCLUSIONS: Our results provide a framework for further studies into the mechanisms of radioresistance and serve as a basis to construct a predictive model of radioresistance in breast cancer. Ribosome may participate in the radioresistance of breast cancer, which provides new insights into the proteomic characteristics of the mechanisms of radioresistance.

Mechanical properties evaluation of metacarpophalangeal joint prosthesis with new titanium-nickel memory alloy: a cadaver study.

OBJECTIVE: Ni-Ti memory alloys are unusual materials for hard-tissue replacement because of their unique superelasticity, good biocompatibility, high strength, low specific gravity, low magnetism, wear resistance, corrosion resistance and fatigue resistance. The current study aims to evaluate its mechanical properties and provide biomechanical basis for the clinical application of the prosthesis. METHODS: Ten adult metacarpophalangeal joint specimens were randomly divided into a prosthesis group (n = 5, underwent metacarpophalangeal joint prosthesis) and a control group (n = 5, underwent sham operation). Firstly, the axial compression strength was tested with BOSE material testing machine to evaluate its biomechanical strength. Secondly, these specimens were tested for strain changes using BOSE material testing machine and GOM non-contact optical strain measurement system to evaluate the stress changes. Thirdly, fatigue test was performed between groups. Lastly, the mechanical wear of the metacarpophalangeal joint prosthesis was tested with ETK5510 material testing machine to study its mechanical properties. RESULTS: Axial compression stiffness in the prosthesis group was greater than that in the control group in terms of 30 ° and 60 ° flexion positions (P < 0.05). There was no statistically significant difference between two groups with regards to axial compression stiffness and stress change test (P > 0.05). In the fatigue wear test, the mean mass loss in the prosthesis group's prosthesis was 17.2 mg and 17.619 mm3, respectively. The mean volume wear rate was 0.12%. There was no statistically significant difference in the maximum pull-out force of the metacarpal, phalangeal, and polymer polyethylene pads between the prosthesis group and the control group specimens. CONCLUSIONS: Ni-Ti memory alloy metacarpophalangeal joint prosthesis conforms to the biomechanical characteristics of metacarpophalangeal joints without implants, and the fatigue strength can fully meet the needs of metacarpophalangeal joint activities after joint replacement.

Selective activation of STAT3 and STAT5 dictates the fate of myeloid progenitor cells.

The molecular programs that govern the directed differentiation of myeloid progenitor cells are still poorly defined. Using a previously established immortalized, phenotypically normal myeloid progenitor cell model mEB8-ER, we unveil a new mechanism mediated by STAT5 and STAT3 at a bifurcation point of myeloid progenitor cell-fate specification. We find that myeloid progenitor cells can spontaneously differentiate into neutrophils with a basal level of STAT3 phosphorylation, which is enhanced by G-CSF treatment or STAT3 over-expression, leading to elevated neutrophil differentiation. Reduced STAT3 phosphorylation caused by GM-CSF treatment, STAT3 specific inhibitor, or STAT3 depletion leads to attenuated myeloid differentiation into neutrophils, while elevating differentiation into monocytes/macrophages. In contrast, STAT5 appears to have an antagonistic function to STAT3. When activated by GM-CSF, STAT5 promotes myeloid differentiation into monocytes/macrophages but inhibits neutrophil differentiation. At the mechanistic level, GM-CSF activates STAT5 to up-regulate SOCS3, which attenuates STAT3 phosphorylation and consequently neutrophil differentiation, while enhancing monocyte/macrophage differentiation. Furthermore, inhibition of STAT5 and STAT3 in primary myeloid progenitors recapitulates the results from the mEB8-ER model. Together, our findings provide new mechanistic insights into myeloid differentiation and may prove useful for the diagnosis and treatment of diseases related to abnormal myeloid differentiation.

The prognostic value and biological functions of HFM1 in breast cancer.

Aim: HFM1 has been reported to be associated with meiosis and ovarian insufficiency, but its role in tumors remains unknown. This study aims to explore the functions and potential mechanism of HFM1 in breast cancer. Methods: Several databases, protein-protein interactions, gene ontology and the Kyoto Encyclopedia of Genes and Genomes were used for bioinformatic analysis. Tissue microarrays and cell viability assays were used to detect the expression of HFM1 and tamoxifen resistance, respectively. Results: HFM1 was downregulated in breast cancer with poor prognosis and may modulate DNA damage repair pathways and immune infiltration. Moreover, HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Conclusion: We presented a first study on biological functions and potential mechanisms of HFM1 in cancers.

The role and function of the protein HFM1 in tumors remains unknown. We explored the functions and potential mechanism of HFM1 in breast cancer through several known databases, clinical samples and cell experiments. We found that HFM1 was downregulated in breast cancer with a poor prognosis. HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Here we first put forward the relationship between HFM1 and the prognosis of breast cancer, and provided relevant clues for mechanism exploration.

Physical distance to sensory-motor landmarks predicts language function.

Auditory language comprehension recruits cortical regions that are both close to sensory-motor landmarks (supporting auditory and motor features) and far from these landmarks (supporting word meaning). We investigated whether the responsiveness of these regions in task-based functional MRI is related to individual differences in their physical distance to primary sensorimotor landmarks. Parcels in the auditory network, that were equally responsive across story and math tasks, showed stronger activation in individuals who had less distance between these parcels and transverse temporal sulcus, in line with the predictions of the "tethering hypothesis," which suggests that greater proximity to input regions might increase the fidelity of sensory processing. Conversely, language and default mode parcels, which were more active for the story task, showed positive correlations between individual differences in activation and sensory-motor distance from primary sensory-motor landmarks, consistent with the view that physical separation from sensory-motor inputs supports aspects of cognition that draw on semantic memory. These results demonstrate that distance from sensorimotor regions provides an organizing principle of functional differentiation within the cortex. The relationship between activation and geodesic distance to sensory-motor landmarks is in opposite directions for cortical regions that are proximal to the heteromodal (DMN and language network) and unimodal ends of the principal gradient of intrinsic connectivity.

Collagen Peptides as a Hypoxia-Inducible Factor-2α-Stabilizing Prolyl Hydroxylase Inhibitor to Stimulate Intestinal Iron Absorption by Upregulating Iron Transport Proteins.

Iron intervention is not always safe and effective to correct iron deficiency. Host iron absorption stimulation is emerging as a promising adjunctive/alternative treatment. Here, porcine collagen hydrolysate (CH) and collagen-derived dipeptide prolyl-hydroxyproline, rather than collagen amino acids, namely, glycine, proline, and hydroxyproline, were found to increase cellular iron reduction, absorption, and transportation, to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin (FPN), and hephaestin, and to nongenomically activate hypoxia-inducible factor-2α signaling in polarized Caco-2 cells. Prolyl-hydroxyproline showed both competitive and uncompetitive inhibition of recombinant human prolyl hydroxylase-3 activity with EC50 and Ki values of 10.62 and 6.73 µM, respectively. Docking simulations revealed collagen peptides as iron chelators and/or steric hindrances for prolyl hydroxylase-3. CH and prolyl-hydroxyproline acutely increased duodenal hypoxia-inducible factor-2α stability and Dcytb, DMT1, FPN, and hephaestin transcription in rats. Overall, collagen peptides act as a hypoxia-inducible factor-2α-stabilizing prolyl hydroxylase inhibitor to stimulate intestinal iron absorption.

Evaluation of the freshness of rainbow trout (Oncorhynchus mykiss) fillets by the NIR, E-nose and SPME-GC-MS.

A comparison study on the freshness of rainbow trout (Oncorhynchus mykiss) fillets in the course of their sale was performed using near-infrared spectroscopy (NIRS), solid-phase microextraction combined with gas chromatography-mass spectrometry (SPME-GC-MS), and the electronic nose (E-nose) technique. Quantitative analysis of the volatile salt nitrogen (TVB-N) of rainbow trout fillets with different freshness using NIR combined with the partial least squares (PLS) method revealed that the predicted values of TVB-N of the samples were significantly correlated with the true values (P < 0.01). SPME-GC-MS combined with E-nose analysis demonstrated that there were significant differences in the volatile flavor components of rainbow trout fillets at different freshness, and E-nose combined with principal component analysis (PCA) and linear discriminant analysis (LDA) could achieve rapid and non-destructive freshness ranking of rainbow trout fillets based on volatile flavor characteristics. Consequently, the NIRS and E-nose non-destructive testing techniques are capable of acting as rapid screening tools for detecting the freshness of rainbow trout fillets during their sale.

Perceptual coupling and decoupling of the default mode network during mind-wandering and reading.

While reading, our mind can wander to unrelated autobiographical information, creating a perceptually decoupled state detrimental to narrative comprehension. To understand how this mind-wandering state emerges, we asked whether retrieving autobiographical content necessitates functional disengagement from visual input. In Experiment 1, brain activity was recorded using functional magnetic resonance imaging (fMRI) in an experimental situation mimicking naturally occurring mind-wandering, allowing us to precisely delineate neural regions involved in memory and reading. Individuals read expository texts and ignored personally relevant autobiographical memories, as well as the opposite situation. Medial regions of the default mode network (DMN) were recruited during memory retrieval. In contrast, left temporal and lateral prefrontal regions of the DMN, as well as ventral visual cortex, were recruited when reading for comprehension. Experiment two used functional connectivity both at rest and during tasks to establish that (i) DMN regions linked to memory are more functionally decoupled from regions of ventral visual cortex than regions in the same network engaged when reading; and (ii) individuals with more self-generated mental contents and poorer comprehension, while reading in the lab, showed more decoupling between visually connected DMN sites important for reading and primary visual cortex. A similar pattern of connectivity was found in Experiment 1, with greater coupling between this DMN site and visual cortex when participants reported greater focus on reading in the face of conflict from autobiographical memory cues; moreover, the retrieval of personally relevant memories increased the decoupling of these sites. These converging data suggest we lose track of the narrative when our minds wander because generating autobiographical mental content relies on cortical regions within the DMN which are functionally decoupled from ventral visual regions engaged during reading.

As your eyes scan these words, you may be thinking about what to make for dinner, how to address an unexpected hurdle at work, or how many emails are sitting, unread, in your inbox. This type of mind-wandering disrupts our focus and limits how much information we comprehend, whilst also being conducive to creative thinking and problem-solving. Despite being an everyday occurrence, exactly how our mind wanders remains elusive. One possible explanation is that the brain disengages from visual information from the external world and turns its attention inwards. A greater understanding of which neural circuits are involved in this process could reveal insights about focus, attention, and reading comprehension. Here, Zhang et al. investigated whether the brain becomes disengaged from visual input when our mind wanders while reading. Recalling personal events was used as a proxy for mind-wandering. Brain activity was recorded as participants were shown written statements; sometimes these were preceded by cues to personal memories. People were asked to focus on reading the statements or they were instructed to concentrate on their memories while ignoring the text. The analyses showed that recalling memories and reading stimulated distinct parts of the brain, which were in direct competition during mind-wandering. Further work examined how these regions were functionally connected. In individuals who remained focused on reading despite memory cues, the areas activated by reading showed strong links to the visual cortex. Conversely, these reading-related areas became 'decoupled' from visual processing centres in people who were focusing more on their internal thoughts. These results shed light on why we lose track of what we are reading when our mind wanders: recalling personal memories activates certain brain areas which are functionally decoupled from the regions involved in processing external information ­ such as the words on a page. In summary, the work by Zhang et al. builds a mechanistic understanding of mind-wandering, a natural feature of our daily brain activity. These insights may help to inform future interventions in education to improve reading, comprehension and focus.

Perceptual coupling and decoupling are associated with individual differences in working memory encoding and maintenance.

Working memory (WM) allows goal-relevant information to be encoded and maintained in mind, even when the contents of WM are incongruent with the immediate environment. While regions of heteromodal cortex are important for WM, the neural mechanisms that relate to individual differences in the encoding and maintenance of goal-relevant information remain unclear. Here, we used behavioral correlates of two large-scale heteromodal networks at rest, the default mode (DMN) and frontoparietal (FPN) networks, to understand their contributions to distinct features of WM. We assessed each individual's ability to resist distracting information during the encoding and maintenance phases of a visuospatial WM task. Individuals with stronger connectivity of DMN with medial visual and retrosplenial cortex were less affected by encoding distraction. Conversely, weaker connectivity of both DMN and FPN with visual regions was associated with better WM performance when target information was no longer in the environment and distractors were presented in the maintenance phase. Our study suggests that stronger coupling between heteromodal cortex and visual-spatial regions supports WM encoding by reducing the influence of concurrently presented distractors, while weaker visual coupling is associated with better maintenance of goal-relevant information because it relates to the capacity to ignore task-irrelevant changes in the environment.

Intrinsic connectivity of left ventrolateral prefrontal cortex predicts individual differences in controlled semantic retrieval.

Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.

A comprehensive bioinformatic analysis of RanBP9 expression and its relation to prognosis in human breast cancer.

Aim: To explore the role of RanBP9 in breast cancer. Materials & methods: Oncomine, TIMER, GEPIA, UALCAN, c-BioPortal databases and tissue microarray analysis were used in this study. Results: The expression level of RanBP9 is elevated in breast cancer tissues, which is associated with poor prognosis in breast cancer patients. RanBP9 exhibits genetic alterations and a decreased methylation level in cancer tissues. RanBP9 may also regulate cell cycle progression and is linked to tumor purity and the infiltrating levels of immune cells. Conclusions:RanBP9 may correlate with prognosis and immune infiltration in breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.

Lay abstract RanBP9 has diverse function in various tumor types. However, the role of RanBP9 in breast cancer remains to be explored. In this study, we investigated the gene expression of RanBP9 using databases and clinical samples. We found the expression level of RanBP9 is raised in breast cancer tissues and is associated with poor prognosis for breast cancer patients. RanBP9 may be involved in the regulation of the cell cycle and related to tumor immunity. Overall, we found that RanBP9 may correlate with prognosis and immune infiltration of breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.

Finite Element Analysis of an Improved Correction System for Spinal Deformity.

BACKGROUND/AIM: Surgical treatment for spinal deformity aims to correct malformation, release the nerves, and reconstruct spinal stability. To explore and develop a new improved spinal correction system (ISCS) for clinical application, we studied the stability and biomechanical characteristics of the ISCS through finite element analysis and comparison of the ISCS with the pedicle screw and rod system (PSRS). PATIENTS AND METHODS: Using L1-L3 CT image data of a normal adult male lumbar spine for establishment of L1-L3 finite element model, we established posterior internal fixation models for a comparative finite element analysis of PSRS and ISCS. An axial load of 500 N and a moment of 10 N•m were applied to L1 to simulate flexion, extension, lateral bending, and axial rotation. Stress distribution characteristics, load sharing, strain bending stiffness and strain angle change of the models were measured. RESULTS: In flection and extension directions, the maximum stress of the L2 vertebral body and the L1/2 and L2/3 discs in PSRS was less than that of ISCS. In lateral bending and axial rotation directions, the maximum stress between PSRS and ISCS was similar. However, the stress shielding rate of L2, L1/2, and L2/3 intervertebral discs in ISCS was significantly lower than that of PSRS. We also found that both models had similar angular displacement and maximum displacement in lateral bending direction, but PSRS had a lower angular displacement and maximum displacement in flection and extension directions. Finally, we showed that PSRS had similar angular displacement and a lower maximum displacement compared with ISCS in axial rotation, whereas ISCS had lower bending stiffness than PSRS in different directions. CONCLUSION: ISCS can effectively fix spinal deformities compared to PSRS. ISCS provides a new option for orthopedic surgery treatment of scoliosis and, therefore, warrants further clinical studies in patients with other spinal deformities.

The neural correlates of ongoing conscious thought.

A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the experience and context dependence of patterns of ongoing thought. These studies reveal that systems linked to attention and control are important for organizing experience in response to changing environmental demands. These studies also establish a role of the default mode network beyond task-negative or purely episodic content, for example, implicating it in the level of vivid detail in experience in both task contexts and in spontaneous self-generated experiential states. Together, this work demonstrates that the landscape of ongoing thought is reflected in the activity of multiple neural systems, and it is important to distinguish between processes contributing to how the experience unfolds from those linked to how these experiences are regulated.