Stimulus-responsive and task-dependent activations in occipital regions during pitch perception by early blind listeners.

Although it has been established that cross-modal activations occur in the occipital cortex during auditory processing among congenitally and early blind listeners, it remains uncertain whether these activations in various occipital regions reflect sensory analysis of specific sound properties, non-perceptual cognitive operations associated with active tasks, or the interplay between sensory analysis and cognitive operations. This fMRI study aimed to investigate cross-modal responses in occipital regions, specifically V5/MT and V1, during passive and active pitch perception by early blind individuals compared to sighted individuals. The data showed that V5/MT was responsive to pitch during passive perception, and its activations increased with task complexity. By contrast, widespread occipital regions, including V1, were only recruited during two active perception tasks, and their activations were also modulated by task complexity. These fMRI results from blind individuals suggest that while V5/MT activations are both stimulus-responsive and task-modulated, activations in other occipital regions, including V1, are dependent on the task, indicating similarities and differences between various visual areas during auditory processing.

Developmental plasticity of the structural network of the occipital cortex in congenital blindness.

The occipital cortex is the visual processing center in the mammalian brain. An unanswered scientific question pertains to the impact of congenital visual deprivation on the development of various profiles within the occipital network. To address this issue, we recruited 30 congenitally blind participants (8 children and 22 adults) as well as 31 sighted participants (10 children and 21 adults). Our investigation focused on identifying the gray matter regions and white matter connections within the occipital cortex, alongside behavioral measures, that demonstrated different developmental patterns between blind and sighted individuals. We discovered significant developmental changes in the gray matter regions and white matter connections of the occipital cortex among blind individuals from childhood to adulthood, in comparison with sighted individuals. Moreover, some of these structures exhibited cognitive functional reorganization. Specifically, in blind adults, the posterior occipital regions (left calcarine fissure and right middle occipital gyrus) showed reorganization of tactile perception, and the forceps major tracts were reorganized for braille reading. These plastic changes in blind individuals may be attributed to experience-dependent neuronal apoptosis, pruning, and myelination. These findings provide valuable insights into the longitudinal neuroanatomical and cognitive functional plasticity of the occipital network following long-term visual deprivation.

The influence of guide stabilizers and their application sequences on trueness and precision of surgical guides in free end situations: An in vitro analysis.

OBJECTIVES: To evaluate the impact of guide stabilizers and their application sequences on implant placement accuracy of guided implant surgery in multiple teeth loss at free end. MATERIALS AND METHODS: In this study, 96 implants were placed in the regions of #34, #36, and #37 of 32 identical mandibular models. The influence of using guide stabilizers or not (group A and group B) and various guide stabilizers application sequences (group B: #34 → #36 → #37; group C: #36 → #34 → #37; group D: #37 → #34 → #36) on implant placement trueness and precision was investigated. Data were analyzed using T-tests and one-way ANOVA. RESULTS: Group B showed significant benefits in enhancing implant placement precision. Compared to group A, it resulted in reducing 3D-deviation at crest and 2D deviation in vestibular-oral direction at both crest and apex. Furthermore, group D demonstrated greater improvement in global implant placement precision by reducing 2D deviation in mesial-distal direction at both crest and apex. Among the three different stabilizer application sequences, group D exhibited the highest level of implant placement precision. CONCLUSIONS: In cases of missing teeth at distal free end, the use of guide stabilizers and their application sequences does not have a significant impact on implant placement trueness. However, they do improve implant placement precision compared to methods that do not utilize guide stabilizers. Specifically, applying a guide stabilizer first at the furthest implant site to change teeth loss classification from free end to edentulous space with posterior support is the most reliable sequence.

DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation.

DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.

The influence of visual deprivation on the development of the thalamocortical network: Evidence from congenitally blind children and adults.

The thalamus is heavily involved in relaying sensory signals to the cerebral cortex. A relevant issue is how the deprivation of congenital visual sensory information modulates the development of the thalamocortical network. The answer is unclear because previous studies on this topic did not investigate network development, structure-function combinations, and cognition-related behaviors in the same study. To overcome these limitations, we recruited 30 congenitally blind subjects (8 children, 22 adults) and 31 sighted subjects (10 children, 21 adults), and conducted multiple analyses [i.e., gray matter volume (GMV) analysis using the voxel-based morphometry (VBM) method, resting-state functional connectivity (FC), and brain-behavior correlation]. We found that congenital blindness elicited significant changes in the development of GMV in visual and somatosensory thalamic regions. Blindness also resulted in significant changes in the development of FC between somatosensory thalamic regions and visual cortical regions as well as advanced information processing regions. Moreover, the somatosensory thalamic regions and their FCs with visual cortical regions were reorganized to process high-level tactile language information in blind individuals. These findings provide a refined understanding of the neuroanatomical and functional plasticity of the thalamocortical network.

Understanding Dynamics of Nonlinear Representation Learning and Its Application.

Representations of the world environment play a crucial role in artificial intelligence. It is often inefficient to conduct reasoning and inference directly in the space of raw sensory representations, such as pixel values of images. Representation learning allows us to automatically discover suitable representations from raw sensory data. For example, given raw sensory data, a deep neural network learns nonlinear representations at its hidden layers, which are subsequently used for classification (or regression) at its output layer. This happens implicitly during training through minimizing a supervised or unsupervised loss. In this letter, we study the dynamics of such implicit nonlinear representation learning. We identify a pair of a new assumption and a novel condition, called the on-model structure assumption and the data architecture alignment condition. Under the on-model structure assumption, the data architecture alignment condition is shown to be sufficient for the global convergence and necessary for global optimality. Moreover, our theory explains how and when increasing network size does and does not improve the training behaviors in the practical regime. Our results provide practical guidance for designing a model structure; for example, the on-model structure assumption can be used as a justification for using a particular model structure instead of others. As an application, we then derive a new training framework, which satisfies the data architecture alignment condition without assuming it by automatically modifying any given training algorithm dependent on data and architecture. Given a standard training algorithm, the framework running its modified version is empirically shown to maintain competitive (practical) test performances while providing global convergence guarantees for deep residual neural networks with convolutions, skip connections, and batch normalization with standard benchmark data sets, including MNIST, CIFAR-10, CIFAR-100, Semeion, KMNIST, and SVHN.

Highly Sensitive Multifunctional Electronic Skin Based on Nanocellulose/MXene Composite Films with Good Electromagnetic Shielding Biocompatible Antibacterial Properties.

Electronic skin has aroused extensive research interest due to high similarity with human skin. Realizing a multifunctional electronic skin that is highly consistent with skin functions and endowed with more other functions is now a more urgent need and important challenge. Here, we use 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibril (TOCN) dispersion and highly conductive Ti3C2TX dispersion to prepare TOCN/Ti3C2TX composite film through vacuum-assisted filtration. The obtained composite film imitating the nacre-like lamellar structure of natural shells has good mechanical properties (124.6 MPa of tensile strength). Meanwhile, the composite film also showed excellent electromagnetic shielding performance (36 dB), biocompatibility, and antibacterial properties. In addition, the piezoresistive sensor assembled from the composite film exhibited a high sensitivity (11.6 kPa-1), fast response and recovery time (≤10 ms), ultralow monitoring limit (0.2 Pa), and long-term stability (>10 000 cycles). It also could detect human daily activities such as finger bent, chewing, and so on.

Retinoic Acid Receptor Gamma (RARγ) Promotes Cartilage Destruction through Positive Feedback Activation of NF-κB Pathway in Human Osteoarthritis.

Osteoarthritis (OA) is a severe inflammation-related disease which leads to cartilage destruction. The retinoic acid receptor gamma (RARγ) has been indicated to be involved in many inflammation processes. However, the role and mechanism of RARγ in cartilage destruction caused by inflammation in OA are still unknown. Here, we demonstrated that the RARγ was highly expressed in chondrocytes of OA patients compared with healthy people and was positively correlated with the damage degree of cartilage in OA. Cytokine TNF-α promoted the transcription and expression of RARγ through activating the NF-κB pathway in OA cartilage. In addition, the overexpression of RARγ resulted in the upregulation of matrix degradation and inflammation associated genes and downregulation of differentiation and collagen production genes in human normal chondrocyte C28/I2 cells. Mechanistically, overexpression of RARγ could increase the level of p-IκBα and p-P65 to regulate the expression of downstream genes. RARγ and IκBα also could interact with each other and had the same localization in C28/I2 cells. Moreover, the SD rats OA model induced by monosodium iodoacetate indicated that CD437 (RARγ agonist) and TNF-α accelerated the OA progression, including more severe cartilage layer destruction, larger knee joint diameter, and higher serum ALP levels, while LY2955303 (RARγ inhibitor) showed the opposite result. RARγ was also highly expressed in OA group and even higher in TNF-α group. In conclusion, RARγ/NF-κB positive feedback loop was activated by TNF-α in chondrocyte to promote cartilage destruction. Our data not only propose a novel and precise molecular mechanism for OA disease but also provide a prospective strategy for the treatment.

Sex differences in hemispheric lateralization of attentional networks.

Males and females differ in various abilities. However, sex differences in hemispheric lateralization of attentional processing are still not well-understood. Using a lateralized version of the attentional network test that combines the Posner cueing paradigm and visual field methodology, we aimed to examine sex differences in the lateralization of several attentional processes including alerting, executive control, orienting benefit, reorienting, and orienting cost. Fifty-six females and 59 males participated in this study. We found a left visual field (right hemisphere) advantage for alerting defined by the differences between no-cue and center-cue conditions in the male group, but it was mainly attributed to the left visual field advantage in the no-cue condition. In contrast, the female group exhibited a left visual field advantage in the center-cue condition. Both groups showed preferences to the left visual field for reorienting and orienting cost, but females exhibited larger effects. This indicates that the two sexes exhibit similarities in terms of the lateralization of these two attentional processes. Furthermore, the interactions between executive control and reorienting/orienting cost were more efficient in males than in females. The current study highlights sex differences in the hemispheric lateralization of attentional networks and possible underlying neural substrates.

Superiority of blind over sighted listeners in voice recognition.

The current study examined whether the blind are superior to sighted listeners in voice recognition. Three subject groups, including 17 congenitally blind, 18 late blind, and 18 sighted, showed no significant differences in the immediate voice recognition test. In the delayed test conducted two weeks later, however, both congenitally blind and late blind groups performed better than the sighted with no significant difference between the two blind groups. These results partly confirmed the anecdotal observation about the blind's superiority in voice recognition, which resides mainly in delayed memory phase but not in immediate recall and generalization phase.

Perception of musical melody and rhythm as influenced by native language experience.

This study used the Musical Ear Test [Wallentin, Nielsen, Friis-Olivarius, Vuust, and Vuust (2010). Learn. Indiv. Diff. 20, 188-196] to compare musical aptitude of native Japanese and Chinese speakers. Although the two groups had similar overall accuracy, they showed significant differences in subtest performance. Specifically, the Chinese speakers outperformed the Japanese counterparts on the melody subtest, but the reverse was observed on the rhythm subtest. Within-group comparisons revealed that Chinese speakers performed better on the melody subtest than the rhythm subtest, while Japanese speakers showed an opposite trend. These results indicate that native language pitch and durational patterns of the listener can have a profound effect on the perception of music melody and rhythm, respectively, reflecting language-to-music transfer of learning.

Congenital blindness enhances perception of musical rhythm more than melody in Mandarin speakers.

This study adopted the Musical Ear Test [Wallentin, Nielsen, Friis-Olivarius, Vuust, and Vuust (2010). Learn. Indiv. Diff. 20, 188-196] to compare musical competence of sighted and congenitally blind Mandarin speakers. On the rhythm subtest, the blind participants outperformed the sighted. On the melody subtest, however, the two groups performed equally well. Compared with sighted speakers of non-tonal languages reported in previous studies [Wallentin, Nielsen, Friis-Olivarius, Vuust, and Vuust (2010). Learn. Indiv. Diff. 20, 188-196; Bhatara, Yeung, and Nazzi (2015). J. Exp. Psychol. Hum. Percept. Perform. 41(2), 277-282], sighted Mandarin speakers performed better only on the melody subtest. These results indicate that tonal language experience and congenital blindness exert differential influences on musical aptitudes with rhythm perception reflecting a cross-modal compensation effect and melody perception dominated by a cross-domain language-to-music transfer effect.

Use of semantic context and F0 contours by older listeners during Mandarin speech recognition in quiet and single-talker interference conditions.

This study followed up Wang, Shu, Zhang, Liu, and Zhang [(2013). J. Acoust. Soc. Am. 34(1), EL91-EL97] to investigate factors influencing older listeners' Mandarin speech recognition in quiet vs single-talker interference. Listening condition significantly interacted with F0 contours but not with semantic context, revealing that natural F0 contours provided benefit in the interference condition whereas semantic context contributed similarly to both conditions. Furthermore, the significant interaction between semantic context and F0 contours demonstrated the importance of semantic context when F0 was flattened. Together, findings from the two studies indicate that aging differentially affects tonal language speakers' dependence on F0 contours and semantic context for speech perception in suboptimal conditions.

Estimation and Inference for High-Dimensional Generalized Linear Models with Knowledge Transfer.

Transfer learning provides a powerful tool for incorporating data from related studies into a target study of interest. In epidemiology and medical studies, the classification of a target disease could borrow information across other related diseases and populations. In this work, we consider transfer learning for high-dimensional generalized linear models (GLMs). A novel algorithm, TransHDGLM, that integrates data from the target study and the source studies is proposed. Minimax rate of convergence for estimation is established and the proposed estimator is shown to be rate-optimal. Statistical inference for the target regression coefficients is also studied. Asymptotic normality for a debiased estimator is established, which can be used for constructing coordinate-wise confidence intervals of the regression coefficients. Numerical studies show significant improvement in estimation and inference accuracy over GLMs that only use the target data. The proposed methods are applied to a real data study concerning the classification of colorectal cancer using gut microbiomes, and are shown to enhance the classification accuracy in comparison to methods that only use the target data.

What Factors Contribute to Reading in ADHD: Examining Reading-Related Skills in Children With ADHD Only/Comorbid Developmental Dyslexia.

BACKGROUND: ADHD and developmental dyslexia (DD) frequently co-occur. However, it is unclear why some children with ADHD acquire DD while others do not. METHODS: A total of 830 children (including typically developing controls, ADHD only, DD only, and ADHD + DD groups) of two ages (younger: first-third grade; older: fourth-sixth grade) were assessed on measures of reading ability and reading-related skills. RESULTS: The clinical groups had different degrees of impairment in each reading-related skill. Regression results found that the four groups had different skills in predicting reading ability in younger and older grades. Especially, rapid automatized naming (RAN) was the only predictor of reading ability in children with ADHD only. CONCLUSIONS: The study highlights that RAN plays an important role in the reading development of children with ADHD only, reflecting the possible protective role of RAN in reading development.

DPY30 knockdown suppresses colorectal carcinoma progression via inducing Raf1/MST2-mediated apoptosis.

Colorectal Carcinoma (CRC) is one of the most common malignant tumors of the digestive tract, with a high mortality rate. DPY30 is one of the core subunits of the histone methyltransferase complex, which was involved in many cancer processes. However, the role of DPY30 in the occurrence and progression of CRC remains unclear. In this study, we sought to evaluate the role and mechanism of DPY30 in CRC cells apoptosis. Here, we identified that knockdown of DPY30 significantly inhibited the HT29 and HCT116 cells proliferation in vitro. Moreover, the knockdown of DPY30 significantly increased the apoptosis rate and promoted the expression of apoptosis-related proteins in CRC cells. Meanwhile, DPY30 knockdown promoted CRC cells apoptosis through endogenous programmed death and in a caspase activation-dependent manner. Furthermore, RNA-seq analysis revealed that the action of DPY30 is closely related to the apoptosis biological processes, and screened its potential effectors Raf1. Mechanistically, DPY30 downregulation promotes MST2-induced apoptosis by inhibiting Raf1 transcriptional activity through histone H3 lysine 4 trimethylation (H3K4me3). In vivo experiments showed that DPY30 was correlated with Raf1 in nude mouse subcutaneous xenografts tissues significantly. Clinical colorectal specimens further confirmed that overexpression of DPY30 in malignant tissues was significantly correlated with Raf1 level. The vital role of the DPY30/Raf1/MST2 signaling axis in the cell death and survival rate of CRC cells was disclosed, which provides potential new targets for early diagnosis and clinical treatment of CRC.

Effective surface passivation of GaAs nanowire photodetectors by a thin ZnO capping.

The III-V nanowire (NW) structure is a good candidate for developing photodetectors. However, high-density surface states caused by the large surface-to-volume ratio severely limit their performance, which is difficult to solve in conventional ways. Here, a robust surface passivation method, using a thin layer of ZnO capping, is developed for promoting NW photodetector performance. 11 cycles of ZnO, grown on pure zinc blende high-quality GaAs NWs by atomic layer deposition, significantly alleviates the undesirable effect of the surface states, without noticeable degradation in NW morphology. An average 20-fold increase in micro-photoluminescence intensity is observed for passivated NWs, which leads to the development of detectors with high responsivity, specific detectivity, and optical gain of 9.46 × 105 A W-1, 3.93 × 1014 Jones, and 2.2 × 108 %, respectively, under low-intensity 532 nm illumination. Passivated NW detectors outperform their counterparts treated by conventional methods, so far as we know, which shows the potential and effectiveness of thin ZnO surface passivation on NW devices.

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway.

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

The roles of fundamental frequency contours and sentence context in Mandarin Chinese speech intelligibility.

Flattening the fundamental frequency (F0) contours of Mandarin Chinese sentences reduces their intelligibility in noise but not in quiet. It is unclear, however, how the absence of primary acoustic cue for lexical tones might be compensated with the top-down information of sentence context. In this study, speech intelligibility was evaluated when participants listened to sentences and word lists with or without F0 variations in quiet and noise. The results showed that sentence context partially explained the unchanged intelligibility of monotonous Chinese sentences in quiet and further indicate that F0 variations and sentence context act in concert during speech comprehension.

[Antitumor effect of capsaicin on colorectal carcinoma xenograft in nude mice].

OBJECTIVE: To evaluate the effect of capsaicin on nude mice xenografted with colorectal carcinoma cells, and to explore its mechanism of action. METHODS: A nude mouse model of colorectal cancer was established by subcutaneous inoculation of human colorectal carcinoma HT-29 cells. Terminal deoxynucleotidyl transferase-mediated nicked labeling assay (TUNEL) was undertaken to detect the cell proliferation and apoptosis in the xenograft tissue in nude mice. Immunohistochemical (IHC) staining and Western blot were used to detect the expression of HSP27, Cyt-C and active caspase-3. RESULTS: The tumor growth of the groups C10 and C20 was significantly slower than that of the group NS. The integrated optical density (IOD) of both the group C5 (2532.14 ± 578.11) and group C10 (6364.03 ± 1137.98) was significantly higher than that of the group NS (760.12 ± 238.05), (P < 0.05). The integrated optical density (IOD) of the group C20 was (15743.96 ± 1855.95), significantly higher than that of the groups C10, C5 and NS (all were P < 0.01). Immunohistochemistry showed that the cytoplasmic expression of HSP27 was strongly positive in the group NS, and significantly reduced with the increasing dose of capsaicin in the treated groups. The expression of active caspase-3 and Cyt-C in the group NS was weakly positive, and was significantly increased with the increasing dose of capsaicin in the groups C5 and C10 (P < 0.05), and the expression of active caspase-3 and Cyt-C of the group C20 was significantly higher than that of the groups C5, C10 and NS (P < 0.01). Western blot analysis showed that both the expressions of HSP27 of the group C5 (0.73 ± 0.05) and the group C10 (0.41 ± 0.03) were significantly lower than that of the group NS (P < 0.05). The expression of HSP27 of the group C20 (0.22 ± 0.06) was significantly lower than that of the groups C5, C10 and NS (P < 0.01). The expressions of active-caspase-3 and Cyt-C in the group C5 were (2.57 ± 0.34) and (2.03 ± 0.38), significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C10 were (4.23 ± 0.45) and (3.13 ± 0.44), also significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C20 were (5.78 ± 0.48) and (4.92 ± 0.52), significantly higher than those of the group C5, C10 and NS (P < 0.01). TUNEL analysis showed that there was a significant difference of cell apoptosis in comparison of each two groups. The higher dose of capsaicin was used, the more apoptosis was observed. CONCLUSIONS: Capsaicin can significantly inhibit the tumor growth and induce cell apoptosis in the colorectal carcinoma xenograft in nude mice. Its mechanism of action is possibly related with the down-regulation of HSP27 expression and up-regulation of expression of active caspase-3 and Cyt-C in the colorectal carcinoma xenograft in nude mice.