Bletilla striata carbon dots with alleviating effect of DSS-induced ulcerative colitis.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that significantly affected quality of life for patients. In this study, carbon dots based on Bletilla striata (BS-CDs) were synthesized by hydrothermal method and characterized by optical property analysis. In addition, the study measured the potential effect of BS-CDs on colonic histopathology and inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis. The results suggested that BS-CDs significantly increased colon length, improved colonic histopathology, and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in colitis mice. Taken together, BS-CDs alleviate clinical inflammation by blocking pro-inflammatory cytokines which were expected to be a potential agent for the treatment of colitis.

Long Noncoding RNA Gpr137b-ps Promotes Advanced Atherosclerosis via the Regulation of Autophagy in Macrophages.

BACKGROUND: Current therapies cannot completely reverse advanced atherosclerosis. High levels of amino acids, induced by Western diet, stimulate mTORC1 (mammalian target of rapamycin complex 1)-autophagy defects in macrophages, accelerating atherosclerotic plaque progression. In addition, autophagy-lysosomal dysfunction contributes to plaque necrotic core enlargement and lipid accumulation. Therefore, it is essential to investigate the novel mechanism and molecules to reverse amino acid-mTORC1-autophagy signaling dysfunction in macrophages of patients with advanced atherosclerosis. METHODS: We observed that Gpr137b-ps (G-protein-coupled receptor 137B, pseudogene) was upregulated in advanced atherosclerotic plaques. The effect of Gpr137b-ps on the progression of atherosclerosis was studied by generating advanced plaques in ApoE-/- mice with cardiac-specific knockout of Gpr137b-ps. Bone marrow-derived macrophages and mouse mononuclear macrophage cell line RAW264.7 cells were subjected to starvation or amino acid stimulation to study amino acid-mTORC1-autophagy signaling. Using both gain- and loss-of-function approaches, we explored the mechanism of Gpr137b-ps-regulated autophagy. RESULTS: Our results demonstrated that Gpr137b-ps deficiency led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation. Knockdown of Gpr137b-ps increased autophagy and prevented amino acid-induced mTORC1 signaling activation. As the downstream binding protein of Gpr137b-ps, HSC70 (heat shock cognate 70) rescued the impaired autophagy induced by Gpr137b-ps. Furthermore, Gpr137b-ps interfered with the HSC70 binding to G3BP (Ras GTPase-activating protein-binding protein), which tethers the TSC (tuberous sclerosis complex) complex to lysosomes and suppresses mTORC1 signaling. In addition to verifying that the NTF2 (nuclear transport factor 2) domain of G3BP binds to HSC70 by in vitro protein synthesis, we further demonstrated that HSC70 binds to the NTF2 domain of G3BP through its W90-F92 motif by using computational modeling. CONCLUSIONS: These findings reveal that Gpr137b-ps plays an essential role in the regulation of macrophage autophagy, which is crucial for the progression of advanced atherosclerosis. Gpr137b-ps impairs the interaction of HSC70 with G3BP to regulate amino acid-mTORC1-autophagy signaling, and these results provide a new potential therapeutic direction for the treatment of advanced atherosclerosis.

Working Memory for Spatial Sequences: Developmental and Evolutionary Factors in Encoding Ordinal and Relational Structures.

Sequence learning is a ubiquitous facet of human and animal cognition. Here, using a common sequence reproduction task, we investigated whether and how the ordinal and relational structures linking consecutive elements are acquired by human adults, children, and macaque monkeys. While children and monkeys exhibited significantly lower precision than adults for spatial location and temporal order information, only monkeys appeared to exceedingly focus on the first item. Most importantly, only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used a chunking strategy to compress sequences in working memory. Monkeys did not detect such relational structures, even after extensive training. Monkey behavior was captured by a conjunctive coding model, whereas a chunk-based conjunctive model explained more variance in humans. These age- and species-related differences are indicative of developmental and evolutionary mechanisms of sequence encoding and may provide novel insights into the uniquely human cognitive capacities.SIGNIFICANCE STATEMENT Sequence learning, the ability to encode the order of discrete elements and their relationships presented within a sequence, is a ubiquitous facet of cognition among humans and animals. By exploring sequence-processing abilities at different human developmental stages and in nonhuman primates, we found that only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used an internal language to compress sequences in working memory. The findings provided insights into understanding the origins of sequence capabilities in humans and how they evolve through development to identify the unique aspects of human cognitive capacity, which includes the comprehension, learning, and production of sequences, and perhaps, above all, language processing.

Representation of spatial sequences using nested rules in human prefrontal cortex.

Memory for spatial sequences does not depend solely on the number of locations to be stored, but also on the presence of spatial regularities. Here, we show that the human brain quickly stores spatial sequences by detecting geometrical regularities at multiple time scales and encoding them in a format akin to a programming language. We measured gaze-anticipation behavior while spatial sequences of variable regularity were repeated. Participants' behavior suggested that they quickly discovered the most compact description of each sequence in a language comprising nested rules, and used these rules to compress the sequence in memory and predict the next items. Activity in dorsal inferior prefrontal cortex correlated with the amount of compression, while right dorsolateral prefrontal cortex encoded the presence of embedded structures. Sequence learning was accompanied by a progressive differentiation of multi-voxel activity patterns in these regions. We propose that humans are endowed with a simple "language of geometry" which recruits a dorsal prefrontal circuit for geometrical rules, distinct from but close to areas involved in natural language processing.

Language and Sensory Neural Plasticity in the Superior Temporal Cortex of the Deaf.

Visual stimuli are known to activate the auditory cortex of deaf people, presenting evidence of cross-modal plasticity. However, the mechanisms underlying such plasticity are poorly understood. In this functional MRI study, we presented two types of visual stimuli, language stimuli (words, sign language, and lip-reading) and a general stimulus (checkerboard) to investigate neural reorganization in the superior temporal cortex (STC) of deaf subjects and hearing controls. We found that only in the deaf subjects, all visual stimuli activated the STC. The cross-modal activation induced by the checkerboard was mainly due to a sensory component via a feed-forward pathway from the thalamus and primary visual cortex, positively correlated with duration of deafness, indicating a consequence of pure sensory deprivation. In contrast, the STC activity evoked by language stimuli was functionally connected to both the visual cortex and the frontotemporal areas, which were highly correlated with the learning of sign language, suggesting a strong language component via a possible feedback modulation. While the sensory component exhibited specificity to features of a visual stimulus (e.g., selective to the form of words, bodies, or faces) and the language (semantic) component appeared to recruit a common frontotemporal neural network, the two components converged to the STC and caused plasticity with different multivoxel activity patterns. In summary, the present study showed plausible neural pathways for auditory reorganization and correlations of activations of the reorganized cortical areas with developmental factors and provided unique evidence towards the understanding of neural circuits involved in cross-modal plasticity.

In vitro antioxidant activity of the polysaccharide from Auricularia auricula and its structural characterisation.

A new polysaccharide (AAP) was extracted from Auricularia auricula by water extraction and alcohol precipitation. The antioxidant activity in vitro showed that AAP had a good scavenging effect on ABTS free radicals. Then AAP was purified by DEAE-52 ion exchange chromatography to obtain the purified component pAAP. The structure analysis showed that the molecular weight (Mw) of pAAP was 96.768 kDa, which was composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glu) and galactose (Gal), with the ratio of 0.1:0.157:0.33:2.797:2.881:2.988:0.587, and contained α-pyranose configuration and ß-pyranose configuration. Field emission scanning electron microscopy and atomic force microscopy revealed the special conformation of pAAP in the ring and chain shape.

AgingReG: a curated database of aging regulatory relationships in humans.

Aging and cellular senescence are characterized by a progressive loss of physiological integrity, which could be triggered by aging factors such as physiological, pathological and external factors. Numerous studies have shown that gene regulatory events play crucial roles in aging, increasing the need for a comprehensive repository of regulatory relationships during aging. Here, we established a manually curated database of aging factors (AgingReG, https://bio.liclab.net/Aging-ReG/), focusing on the regulatory relationships during aging with experimental evidence in humans. By curating thousands of published literature, 2157 aging factor entries (1345 aging gene entries, 804 external factor entries and eight aging-related pathway entries) and related regulatory information were manually curated. The regulatory relationships were classified into four types according to their functions: (i) upregulation, which indicates that aging factors upregulate the expression of target genes during aging; (ii) downregulation, which indicates that aging factors downregulate the expression of target genes during aging; (iii) activation, which indicates that aging factors influence the activity of target genes during aging and (iv) inhibition, which indicates that aging factors inhibit the activation of target molecule activity, leading to declined or lost target activity. AgingReG involves 651 upregulating pairs, 632 downregulating pairs, 330 activation-regulating pairs and 34 inhibition-regulating pairs, covering 195 disease types and more than 800 kinds of cells and tissues from 1784 published literature studies. AgingReG provides a user-friendly interface to query, browse and visualize detailed information about the regulatory relationships during aging. We believe that AgingReG will serve as a valuable resource database in the field of aging research. Database URL: https://bio.liclab.net/Aging-ReG/.

A Simple and Compact MR-Compatible Electromagnetic Vibrotactile Stimulator.

We have developed a low-cost electromagnetic vibrotactile stimulator that uses the magnetic field of an MR scanner as a permanent magnet to power a vibrating motor. A simple variable current power supply is controlled by software using a USB data acquisition controller. In our study, the function of our novel stimulator was verified in a vibration frequency discrimination working memory task, in which various ranges of frequencies and amplitudes are delivered in MRI scanner. Furthermore, our functional MRI study revealed activations of the primary and secondary somatosensory cortices during the perception of tactile stimulation. Therefore, the new designed electromagnetic vibrotactile stimulator is capable of generating various frequencies of tactile stimuli and represents a powerful and useful tool for studying somatosensory functions with functional MRI.

Production of Supra-regular Spatial Sequences by Macaque Monkeys.

Understanding and producing embedded sequences in language, music, or mathematics, is a central characteristic of our species. These domains are hypothesized to involve a human-specific competence for supra-regular grammars, which can generate embedded sequences that go beyond the regular sequences engendered by finite-state automata. However, is this capacity truly unique to humans? Using a production task, we show that macaque monkeys can be trained to produce time-symmetrical embedded spatial sequences whose formal description requires supra-regular grammars or, equivalently, a push-down stack automaton. Monkeys spontaneously generalized the learned grammar to novel sequences, including longer ones, and could generate hierarchical sequences formed by an embedding of two levels of abstract rules. Compared to monkeys, however, preschool children learned the grammars much faster using a chunking strategy. While supra-regular grammars are accessible to nonhuman primates through extensive training, human uniqueness may lie in the speed and learning strategy with which they are acquired.