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This study aimed to assess the impact of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery following spinal cord injury (SCI), while also exploring the involvement of the PI3K-AKT signaling pathway in regulating neuronal apoptosis. EPI-NCSCs were isolated from 10-day-old Sprague-Dawley rats and cultured for 48 h to obtain EPI-NCSC-CM. SHSY-5Y cells were subjected with H2O2 treatment to induce apoptosis. Cell viability and survival rates were evaluated using the CCK-8 assay and calcein-AM/PI staining. SCI contusion model was established in adult Sprague-Dawley rats to assess functional recovery, utilizing the Basso, Beattie and Bresnahan (BBB) scoring system, inclined test, and footprint observation. Neurological restoration after SCI was analyzed through electrophysiological recordings. Histological analysis included hematoxylin and eosin (H&E) staining and Nissl staining to evaluate tissue organization. Apoptosis and oxidative stress levels were assessed using TUNEL staining and ROS detection methods. Additionally, western blotting was performed to examine the expression of apoptotic markers and proteins related to the PI3K/AKT signaling pathway. EPI-NCSC-CM significantly facilitated functional and histological recovery in SCI rats by inhibiting neuronal apoptosis through modulation of the PI3K/AKT pathway. Administration of EPI-NCSCs-CM alleviated H2O2-induced neurotoxicity in SHSY-5Y cells in vitro. The use of LY294002, a PI3K inhibitor, underscored the crucial role of the PI3K/AKT signaling pathway in regulating neuronal apoptosis. This study contributes to the ongoing exploration of molecular pathways involved in spinal cord injury (SCI) repair, focusing on the therapeutic potential of EPI-NCSC-CM. The research findings indicate that EPI-NCSC-CM exerts a neuroprotective effect by suppressing neuronal apoptosis through activation of the PI3K/AKT pathway in SCI rats. These results highlight the promising role of EPI-NCSC-CM as a potential treatment strategy for SCI, emphasizing the significance of the PI3K/AKT pathway in mediating its beneficial effects. [ABSTRACT FROM AUTHOR]

METTL3 is an important methyltransferase in N(6)-methyladenosine (m6A) modification. Recently, METTL3 mediates methylation of pri-microRNA (miRNA) to accelerate miRNA maturation, regulating tumor development. This study explored whether METTL3 mediated miR-99a-5p to influence oral squamous cell carcinoma (OSCC) cell metastasis. MiR-99a-5p, ZBTB7A, and MATTL3 expression was measured using quantitative real-time PCR. Biological behaviors were assessed using cell counting kit-8, flow cytometry, Transwell assay, as well as western blot. Luciferase reporter assay evaluated the interaction between miR-99a-5p and ZBTB7A. METTL3-regulated pri-miR-99a-5p processing was determined by RNA binding protein immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays. The consequences clarified that miR-99a-5p was upregulated in OSCC cells. Downregulation of miR-99a-5p suppressed cellular viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and induced apoptosis. ZBTB7A acted as a miR-99a-5p target and reversed the effects on cellular behaviors induced by miR-99a-5p inhibitor. m6A content and METTL3 expression were increased in OSCC cells. METTL3 promoted the m6A modification of pri-miR-99a-5p and thereby facilitated miR-99a-5p processing. Moreover, knockdown of METTL3 inhibited OSCC metastasis by downregulating miR-99a-5p. Taken together, METTL3 promoted miR-99a-5p maturation in an m6A-dependent manner, which further targets ZBTB7A to accelerate the progression of OSCC. These findings suggest potential targets for OSCC therapy. [ABSTRACT FROM AUTHOR]

Background: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. Methods and Results: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. Conclusions: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration. [ABSTRACT FROM AUTHOR]

Chronic pain is a significant public health issue that is often refractory to existing therapies. Here we use a multiomic approach to identify cis-regulatory elements that show differential chromatin accessibility and reveal transcription factor (TF) binding motifs with functional regulation in the rat dorsal root ganglion (DRG), which contain cell bodies of primary sensory neurons, after nerve injury. We integrated RNA-seq to understand how differential chromatin accessibility after nerve injury may influence gene expression. Using TF protein arrays and chromatin immunoprecipitation-qPCR, we confirmed C/EBPγ binding to a differentially accessible sequence and used RNA-seq to identify processes in which C/EBPγ plays an important role. Our findings offer insights into TF motifs that are associated with chronic pain. These data show how interactions between chromatin landscapes and TF expression patterns may work together to determine gene expression programs in rat DRG neurons after nerve injury. [ABSTRACT FROM AUTHOR]

Previous studies suggested that postsynaptic neuroligin-2 may shift from inhibitory toward excitatory function under pathological pain conditions. We hypothesize that nerve injury may increase the expression of spinal MAM-domain GPI-anchored molecule 1 (MDGA1), which can bind to neuroligin-2 and thereby, alter its interactions with postsynaptic scaffolding proteins and increase spinal excitatory synaptic transmission, leading to neuropathic pain. Western blot, immunofluorescence staining, and co-immunoprecipitation studies were conducted to examine the critical role of MDGA1 in the lumbar spinal cord dorsal horn in rats after spinal nerve ligation (SNL). Small interfering ribonucleic acids (siRNAs) targeting MDGA1 were used to examine the functional roles of MDGA1 in neuropathic pain. Protein levels of MDGA1 in the ipsilateral dorsal horn were significantly upregulated at day 7 post-SNL, as compared to that in naïve or sham rats. The increased levels of GluR1 in the synaptosomal membrane fraction of the ipsilateral dorsal horn tissues at day 7 post-SNL was normalized to near sham level by pretreatment with intrathecal MDGA1 siRNA2308, but not scrambled siRNA or vehicle. Notably, knocking down MDGA1 with siRNAs reduced the mechanical and thermal pain hypersensitivities, and inhibited the increased excitatory synaptic interaction between neuroligin-2 with PSD-95, and prevented the decreased inhibitory postsynaptic interactions between neuroligin-2 and Gephyrin. Our findings suggest that SNL upregulated MDGA1 expression in the dorsal horn, which contributes to the pain hypersensitivity through increasing the net excitatory interaction mediated by neuroligin-2 and surface delivery of GluR1 subunit in dorsal horn neurons. [ABSTRACT FROM AUTHOR]

Quite a few studies have been performed based on movie-watching functional connectivity (FC). As compared to its resting-state counterpart, however, there is still much to know about its abilities in individual identifications and individualized predictions. To pave the way for appropriate usage of movie-watching FC, we systemically evaluated the minimum number of time points, as well as the exact functional networks, supporting individual identifications and individualized predictions of apparent traits based on it. We performed the study based on the 7T movie-watching fMRI data included in the HCP S1200 Release, and took IQ as the test case for the prediction analyses. The results indicate that movie-watching FC based on only 15 time points can support successful individual identifications (99.47%), and the connectivity contributed more to identifications were much associated with higher-order cognitive processes (the secondary visual network, the frontoparietal network and the posterior multimodal network). For individualized predictions of IQ, it was found that successful predictions necessitated 60 time points (predicted vs. actual IQ correlation significant at P < 0.05, based on 5,000 permutations), and the prediction accuracy increased logarithmically with the number of time points used for connectivity calculation. Furthermore, the connectivity that contributed more to individual identifications exhibited the strongest prediction ability. Collectively, our findings demonstrate that movie-watching FC can capture rich information about human brain function, and its ability in individualized predictions depends heavily on the length of fMRI scans. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging (RS-fMRI) has great potential for clinical applications. This study aimed to promote the performance of RS-fMRI-based individualized predictive models by introducing effective feature extraction and utilization strategies and making better use of information hidden in RS-fMRI data. We proposed a novel framework named multi-facet BrainNet with connectivity attention (MFBCA) to fulfill the purpose, and the framework is characterized by the following three strategies. First, in addition to the overwhelmingly popular functional connectivity, we also used distance correlation and weighted directed connectivity as multi-facet inputs for MFBCA. Second, a connectivity attention layer was proposed to force MFBCA to focus more on connections that are important for predictions. Finally, a BrainNet-based architecture with a feature fusion module was introduced to facilitate final predictions. We evaluated the performance of MFBCA with predictions of individuals' age and intelligence quotient as test cases based on three public RS-fMRI datasets. The results indicate that MFBCA can effectively utilize the information hidden in RS-fMRI data and outperform baselines. The predicted-vs-actual correlations for age predictions were 0.876 (7.314 years), 0.873 (8.121 years), and 0.681 (3.865 years), and for IQ predictions was 0.615 (4.287). The connectivity attention layer made it possible for us to determine the connections important for individualized predictions. MFBCA can be widely applied to predictions based on neuroimaging data from which connectivity maps can be extracted. Furthermore, the explicit physiological basis for predictions provided by the connectivity attention layer makes MFBCA a profitable choice for clinical applications. [ABSTRACT FROM AUTHOR]

Light exposure can profoundly affect neurological functions and behaviors. Here, we show that short-term exposure to moderate (400 lux) white light during Y-maze test promoted spatial memory retrieval and induced only mild anxiety in mice. This beneficial effect involves the activation of a circuit including neurons in the central amygdala (CeA), locus coeruleus (LC), and dentate gyrus (DG). Specifically, moderate light activated corticotropin-releasing hormone (CRH) positive (+) CeA neurons and induced the release of corticotropin-releasing factor (CRF) from their axon terminals ending in the LC. CRF then activated tyrosine hydroxylase-expressing LC neurons, which send projections to DG and release norepinephrine (NE). NE activated β-adrenergic receptors on CaMKIIα-expressing DG neurons, ultimately promoting spatial memory retrieval. Our study thus demonstrated a specific light scheme that can promote spatial memory without excessive stress, and unraveled the underlying CeA-LC-DG circuit and associated neurochemical mechanisms. A white light exposure scheme in mice activates amygdala circuitry and enhances spatial memory retrieval. [ABSTRACT FROM AUTHOR]

Movie fMRI has been increasingly used in investigations of human brain function. Inter-subject functional correlation (ISFC), which evaluates stimulus-dependent inter-regional synchrony between brains exposed to the same stimulus, is emerging as an influencing measure for movie fMRI data analyses. Before the wide application of ISFC analyses, it will be useful to investigate the degree to which they are similar and different across different movies. Based on the four movie fMRI runs of 178 subjects included in the "human connectome project (HCP) S1200 Release", we evaluated ISFCs throughout the brain and analyzed their consistency across different movies using intra-class correlation (ICC). We also investigated the generalizability of ISFC-based predictive models, which is closely related to their consistency, with sex classification and grip strength prediction used as test cases. The results showed that the intensity of ISFCs was generally weak (0.047). Except a few within-network ones (e.g., ICC of ISFC in the PON was 0.402), ISFCs throughout the brain exhibited low consistency, as indicated by a mean ICC of 0.130. The accuracies for inter-run predictions (60.7-72.8% for sex classification, and R = 0.122–0.275 for grip strength prediction) were much lower than those for intra-run predictions (73.2-83.0% for sex classification, and R = 0.325–0.403 for grip strength prediction), and this indicates poor generalizability of predictive models based on ISFCs. According to these findings, ISFC analyses capture aspects of brain function that are specific to each individual movie, and this specificity should be taken into account (in some cases might be especially useful) in future naturalistic studies. [ABSTRACT FROM AUTHOR]

This study investigated the cognition, information behaviors and preventive behaviors of Taiwanese citizens in the face of the COVID-19 pandemic. An online survey was administered and 610 valid responses were collected. The relationships between demographic variables and optimistic bias, social trust, information credibility, personal protective measures, avoidance of human contact, and immune system strengthening were examined. Results showed that optimistic bias existed, but there was no significant correlation between optimistic bias and personal protective measures. Laypersons had high trust in the government, but also optimistic bias. Gender was the most important predictor; with occupation and region of residence also interacting with different preventive behaviors. People in Taiwan may be overly optimistic in facing the epidemic; relevant information should be properly disclosed to help reduce this bias. Social trust in the government seems to be an important successful factor in the fight against COVID-19 in Taiwan. [ABSTRACT FROM AUTHOR]

The field of research on pain originating from various bone diseases is expanding rapidly, with new mechanisms and targets asserting both peripheral and central sites of action. The scope of research is broadening from bone biology to neuroscience, neuroendocrinology, and immunology. In particular, the roles of primary sensory neurons and non-neuronal cells in the peripheral tissues as important targets for bone pain treatment are under extensive investigation in both pre-clinical and clinical settings. An understanding of the peripheral mechanisms underlying pain conditions associated with various bone diseases will aid in the appropriate application and development of optimal strategies for not only managing bone pain symptoms but also improving bone repairing and remodeling, which potentially cures the underlying etiology for long-term functional recovery. In this review, we focus on advances in important preclinical studies of significant bone pain conditions in the past 5 years that indicated new peripheral neuronal and non-neuronal mechanisms, novel targets for potential clinical interventions, and future directions of research. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have shown that vitamin D levels are inversely related to ulcerative colitis activity, yet evidence from population interventions remains inconsistent. We conducted a systematic review and meta-analysis of randomized-controlled trials to clarify the effect of vitamin D on blood markers in patients with ulcerative colitis. Methods: The PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases were searched for studies published before June 2020. Information was collected regarding serum vitamin D levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and Ca (calcium), and parathyroid hormone (PTH), and ulcerative colitis disease activity index (UCDAI) research data. Results: Seven studies (n = 539) were included in the meta-analysis. Vitamin D supplementation resulted in significant improvements in the serum vitamin D levels (standardized mean difference (SMD) = 0.69, 95% CI (0.36, 1.03), P < 0.001), ESR (weighted mean difference (WMD) = − 1.10, 95% CI (− 1.97, − 0.24), P = 0.01), CRP (SMD = − 0.43, 95% CI (− 0.67, − 0.20), P = 0.0003), and Ca (SMD = 0.92, 95% CI (0.09, 1.74), P = 0.03) but not in other outcomes. According to subgroup analysis, supplementation with vitamin D at a dose of ≥ 300,000 IU/day can improve serum vitamin D levels. Supplementation with a sufficient dose of vitamin D in a short period of time can also improve serum vitamin D levels. According to GRADE method evaluation, the evidence quality was classified as low for the Serum Vitamin D Level and ESR, and very low for the CRP, PTH, Ca, and UCDAI. Conclusions: Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with ulcerative colitis. Different doses of vitamin D and durations of intervention produce different effects. However, due to the limitation of the quality of the included studies, the above conclusions still need to be verified by more high-quality studies and weak clinical recommendations. [ABSTRACT FROM AUTHOR]

Vicatia thibetica de Boiss.: a herb in the family Apiaceae, has been used for over a hundred years as an essential medicinal and edible plant in the Bai ethnic group of Dali City. However, due to the lack of study on plastid genomes of V. thibetica, studies of comparison and phylogeny with other related species remain scarce. In the current study, we assembled, annotated, and characterized the entire chloroplast (cp) genome of V. thibetica through high-throughput sequencing for the first time, compared with published whole chloroplast genomes from the same family. A phylogenetic analysis of the chloroplast genome has also been performed. The whole chloroplast genome of V. thibetica was 145,796 in size and consisted of a large single-copy region (LSC; 92,186 bp), a small single-copy region (SSC; 17,452 bp), and a pair of inverted repeat regions (IRs; 18,079 bp) forming a circular quadripartite structure. Annotation resulted in 128 genes, including 84 protein-coding genes (PCGs), 35 transfer RNA genes (tRNAs), eight ribosomal genes (rRNAs), and one pseudogene. Repeat sequence analysis displayed V. thibetica plastid genome contains 75 simple repeats, 37 long repeats, and 29 tandem repeats. Compared with the cp genome of other Apiaceae species, a common feature was that the IR regions of the genome were more conservative compared to the LSC and SSC regions. Highly variable hotspots included rps16, ndhC-trnV-UAC, clpP, ycf1, and ndhB in the genomes, which supply valuable molecular markers for phylogeny, identification, and classification in the Apiaceae family. The results of phylogenetic analysis strongly supported the genus Vicatia as an independent genus in the family Apiaceae, in which the closest affinities to the related species of Angelica, Peucedanum, and Ligusticum were observed. In conclusion, the first chloroplast genome of Vicatia reported in this study may improve our understanding of phylogenetic relationship of different genera of Apiaceae. In addition, the current data will be valuable as chloroplast genomic resource for species identification and population genetics. [ABSTRACT FROM AUTHOR]

Skeletal interoception regulates bone homeostasis through the prostaglandin E2 (PGE2) concentration in bone. Vertebral endplates undergo ossification and become highly porous during intervertebral disc degeneration and aging. We found that the PGE2 concentration was elevated in porous endplates to generate spinal pain. Importantly, treatment with a high-dose cyclooxygenase 2 inhibitor (celecoxib, 80 mg·kg−1 per day) decreased the prostaglandin E2 concentration and attenuated spinal pain in mice with lumbar spine instability. However, this treatment impaired bone formation in porous endplates, and spinal pain recurred after discontinuing the treatment. Interestingly, low-dose celecoxib (20 mg·kg−1 per day, which is equivalent to one-quarter of the clinical maximum dosage) induced a latent inhibition of spinal pain at 3 weeks post-treatment, which persisted even after discontinuing treatment. Furthermore, when the prostaglandin E2 concentration was maintained at the physiological level with low-dose celecoxib, endplate porosity was reduced significantly, which was associated with decreased sensory nerve innervation and spinal pain. These findings suggest that low-dose celecoxib may help to maintain skeletal interoception and decrease vertebral endplate porosity, thereby reducing sensory innervation and spinal pain in mice. [ABSTRACT FROM AUTHOR]

Comparative analyses of petroleum generation potential, reservoir volume, frackability, and oil mobility were conducted on 102 shale cores from the Dongpu Depression. Results show the shale has high organic matter contents composed of oil-prone type I and type II kerogens within the oil window. Various types of pores and fractures exist in the shale, with a porosity of up to 14.9%. The shale has high brittle mineral contents, extensive fractures, and high potential for oil mobility due to high seepage capacity and overpressure. Although the petroleum generation potential of the shale at Well PS18-8 is relatively greater than that at Well PS18-1, oil content of the latter is greater due to the greater TOC. The porosity and fracture density observed in Well PS18-1 are greater and more conducive to shale oil enrichment. Although the shales in Wells PS18-1 and PS18-8 have similar brittle mineral contents, the former is more favorable for anthropogenic fracturing due to a higher preexisting fracture density. Besides, the shale at Well PS18-1 has a higher seepage capacity and overpressure and therefore a higher oil mobility. The fracture density and overpressure play key roles in shale oil enrichment. [ABSTRACT FROM AUTHOR]

Microglia can modulate spinal nociceptive transmission. Yet, their role in spinal cord stimulation (SCS)-induced pain inhibition is unclear. Here, we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury (CCI) of the sciatic nerve. Male rats received conventional SCS (50 Hz, 80% motor threshold, 180 min, 2 sessions/day) or sham stimulation on days 18–20 post-CCI. SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns. SCS also upregulated the mRNAs of M1-like markers, but not M2-like markers. Inducible NOS protein expression was increased, but brain-derived neurotrophic factor was decreased after SCS. Intrathecal minocycline (1 μg–100 μg), which inhibits microglial activation, dose-dependently attenuated the mechanical hypersensitivity. Pretreatment with low-dose minocycline (1 μg, 30 min) prolonged the SCS-induced pain inhibition. These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain. [ABSTRACT FROM AUTHOR]

Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Nav 1.8 channels. We show that knockout of PGE2 receptor 4 in sensory nerves significantly reduces spinal hypersensitivity. Inhibition of osteoclast formation by knockout Rankl in the osteocytes significantly inhibits LSI-induced porosity of endplates, sensory innervation, and spinal hypersensitivity. Knockout of Netrin-1 in osteoclasts abrogates sensory innervation into porous endplates and spinal hypersensitivity. These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain. Spinal pain is a major clinical problem. Here the authors show that osteoclasts create porous area of endplates of the vertebrae and sensory innervation of porous endplates by Netrin-1 release from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice. [ABSTRACT FROM AUTHOR]

In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury (SCI). Currently, however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation (SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. Yet, its efficacy, benefit profiles, and mechanisms of action in SCI pain remain elusive, due to limited research, methodological weaknesses in previous clinical studies, and a lack of mechanistic exploration of SCS for SCI pain control. We aim to review recent studies and outline the therapeutic potential of different SCS paradigms for traumatic SCI pain. We begin with an overview of its manifestations, classification, potential underlying etiology, and current challenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed. [ABSTRACT FROM AUTHOR]

Electrical stimulation of nerve fibers is used as a therapeutic tool to treat neurophysiological disorders. Despite efforts to model the effects of stimulation, its underlying mechanisms remain unclear. Current mechanistic models quantify the effects that the electrical field produces near the fiber but do not capture interactions between action potentials (APs) initiated by stimulus and APs initiated by underlying physiological activity. In this study, we aim to quantify the effects of stimulation frequency and fiber diameter on AP interactions involving collisions and loss of excitability. We constructed a mechanistic model of a myelinated nerve fiber receiving two inputs: the underlying physiological activity at the terminal end of the fiber, and an external stimulus applied to the middle of the fiber. We define conduction reliability as the percentage of physiological APs that make it to the somatic end of the nerve fiber. At low input frequencies, conduction reliability is greater than 95% and decreases with increasing frequency due to an increase in AP interactions. Conduction reliability is less sensitive to fiber diameter and only decreases slightly with increasing fiber diameter. Finally, both the number and type of AP interactions significantly vary with both input frequencies and fiber diameter. Modeling the interactions between APs initiated by stimulus and APs initiated by underlying physiological activity in a nerve fiber opens opportunities towards understanding mechanisms of electrical stimulation therapies. [ABSTRACT FROM AUTHOR]

In August 2016, multiple large-tonnage transport vehicles passed through the inclined shaft of the Jinjitian coal mine, Yulin, China, over a short period of time, resulting in fracturing of the floor, bearing capacity reduction, liquefaction of the underlying sand layer, and a serious water and sand inrush. The inrush and its sand content increased rapidly, with flows up to 72 m3/h, with up to 16% sand. Fractures appeared in the walls of the shaft and nine subsidence pits formed on the ground surface. As the distance between the shaft roof and floor continued to shorten, the mine faced the risk of flooding. Four remedial measures were rapidly taken. First, where the roof and floor was seriously fractured, cribs were constructed to effectively stop the convergence of the roof and floor. Second, grouting was carried out on the periphery of the shaft sides to seal and block the inrush ducts, reducing the inrush by 52% and eliminating the sand content. Then, the cribs were replaced with arched steel supports for permanent support. Finally, the shaft wall behind the sand layer was reinforced with grout, which reduced the water inrush from 34.8 to 2.5 m3/h. After adoption of these measures, the inclined shaft withstood the transport of large-tonnage coal-mining equipment for two work faces without an increase in water flow, floor fracturing, sand inrush, or other similar problems, indicating that the damaged shaft was well remediated. The measures taken provide a good reference for control of similar disasters. [ABSTRACT FROM AUTHOR]

Substance used during adolescent period increases the risk of psychiatric disorders in later life, but the underlying neural mechanisms remain unclear. We hypothesize that synaptic remodeling and changes of homeostasis in the medial prefrontal cortex (mPFC) following adolescent cocaine exposure may last for a long time, and these modifications may contribute to behavioral deficiencies in adulthood. To address this hypothesis, rats were exposed to cocaine hydrochloride from postnatal day 28 (P28) to P42. When reared to adulthood, rats were subjected to behavioral tests. On P75 and P76, cocaine-experienced rats exhibited increased locomotive and anxiety-like behaviors, as well as impaired non-selective attention. In the cocaine-experienced rats, both levels of synapse-related proteins (synapsin I and PSD-95) and density of synapse and dendrite spine in mPFC were significantly decreased when compared to controls. Unexpected, the expression of molecules related to oxidative stress, inflammation and apoptosis showed no significant changes in mPFC following adolescent cocaine exposure. These findings suggested that adolescent exposure to cocaine induce long-term modification on synapses in mPFC, which might contribute to long-term behavioral outcomes in adulthood. [ABSTRACT FROM AUTHOR]

Rationale: Resveratrol participates in regulating abnormal behaviors in psychostimulant-exposed animals. Objectives: To examine effects of resveratrol on relapse and anxiety-like behaviors in cocaine withdrawn rats and to investigate possible molecular mechanisms underlying resveratrol effects in hippocampus (HP) and prefrontal cortex (PFC). Methods: Conditioned place preference (CPP) assay and elevated plus maze (EPM) test were used to examine cocaine CPP behavior and anxiety-like behaviors in rats, respectively. Resveratrol was administrated to cocaine withdrawn rats. Levels of MDA, GSH and SOD were examined to evaluate oxidative status, and levels of IL-6, IL-1β and TNF α were measured to examine inflammatory status and levels of caspase-3 and BAX was examined to evaluate apoptotic status in HP and PFC. SIRT expression was also examined here. Results: Resveratrol did not affect cocaine CPP behaviors, but attenuated anxiety-like behaviors in cocaine withdrawn rats. Levels of MDA and TNFα in PFC, and levels of MDA, SOD, GSH, IL-6, IL-1β, TNFα, caspase-3 and BAX in HP, but not SIRT1 expression in both regions were significantly changed during cocaine withdrawal period. Except SOD, resveratrol reversed above neurochemical changes induced by cocaine withdrawal. Furthermore, RSV induced a greater upregulation of SIRT1 expression in PFC in cocaine withdrawn rats than that in saline controls. Conclusions: Current findings suggest that resveratrol may influence behaviors in cocaine withdrawn rats. Oxidative stress, inflammation, apoptosis, and SIRT1 signaling pathway in HP or PFC might be involved in mediating effects of RSV on behaviors in cocaine withdrawn rats. [ABSTRACT FROM AUTHOR]

Fingerprint matching is adopted by a large family of indoor localization schemes, where collecting fingerprints is inevitable but all consuming. While the increasingly popular crowdsourcing based approach provides an opportunity to relieve the burden of fingerprints collecting, a number of formidable challenges for such an approach have yet been studied. For instance, querying in a large fingerprints database for matching process takes a lot of time and calculation; fingerprints collected by crowdsourcing lacks of robustness because of heterogeneous devices problem. Those are important challenges which impede practical deployment of the fingerprint matching indoor localization system. In this study, targeting on effectively utilizing and mining large amount fingerprint data, enhancing the robustness of fingerprints under heterogeneous devices' collection and realizing the real time localization response, we propose a crowdsourcing based fingerprints collecting mechanism for indoor localization systems. With the proposed approach, massive raw fingerprints will be divided into small clusters while diverse devices' uploaded fingerprints will be merged for overcoming device heterogeneity, both of which will contribute to reduce response time. We also build a mobile cloud testbed to verify the proposed scheme. Comprehensive real world experiment results indicate that the scheme can provide comparable localization accuracy. [ABSTRACT FROM AUTHOR]

Pelvic organ cross-sensitization, also termed as viscero-visceral referred hyperalgesia, is a major contributor to painful endometriosis. Its underlying mechanism is poorly understood. Clinical and basic studies have shown that gabapentin, a drug that binds to the αδ−1 subunit of voltage-dependent calcium channels (Caαδ−1), is effective in treating chronic visceral pain. Accordingly, we hypothesized that pelvic organ cross-sensitization in painful endometriosis is mediated by an upregulation of Caαδ−1 in the spinal cord. We examined if the dysregulation of spinal Caαδ−1 subunit may play an important role in the development of ectopic growths-to-colon cross-sensitization in a rat model of experimentally-induced endometriosis. Our findings suggest that there was an increased Caαδ−1 expression in the dorsal horn and an ectopic growths-to-colon cross-sensitization in female rats with established endometriosis. Intrathecal administration of gabapentin (300 μg) remarkably reduced the ectopic growths-to-colon cross-sensitization in rats with established endometriosis. Furthermore, intrathecal injection of Caαδ−1 antisense oligodeoxynucleotides reversed the ectopic growths-to-colon cross-sensitization and also normalized the upregulation of spinal Caαδ−1 expression in endometriosis rats. The current study suggests that the upregulation of Caαδ−1 in the spinal cord may contribute to pelvic organ cross-sensitization in painful endometriosis. Our study may provide a biological basis for selectively targeting this pathway to relieve viscero-visceral referred hyperalgesia in patients with painful endometriosis. [ABSTRACT FROM AUTHOR]

Aim:To investigate the effect of chronic nicotine treatment on vascular function and to identify the underlying mechanisms.Methods:Adult rats were treated with nicotine (3 mg·kg−1·d−1, sc) for 6 weeks. After the rats were sacrificed, aortic rings were prepared for detecting vascular reactivity, and thoracic aorta and periaortic fat samples were collected for histological and molecular biology studies.Results:Chronic nicotine treatment significantly reduced periaortic fat, and specifically enhanced smooth muscle relaxation without altering the aortic adventitial fat and endothelium function. Pretreatment with the soluble guanylyl cyclase inhibitor ODQ (3 μmol/L) or PKG inhibitor Rp-8-Br-PET-cGMP (30 μmol/L) abolished the nicotine-induced enhancement of smooth muscle relaxation, whereas the cGMP analogue 8-Br-cGMP could mimic the nicotine-induced enhancement of smooth muscle relaxation. However, the chronic nicotine treatment did not alter PKG protein expression and activity in aortic media.Conclusion:Chronic nicotine treatment enhances vascular smooth muscle relaxation of rats via activation of PKG pathway. [ABSTRACT FROM AUTHOR]

In this study, we developed a methylation-sensitive amplification polymorphism technique to investigate DNA methylation profiles in different tissues and in the early-development stages of the pearl oyster Pinctada fucata ( P. fucata). Methylation levels in adductor muscle, digestive gland, axe foot, heart, and gill ranged from 11.71 to 14.71 %, and significant differences ( P < 0.05) between methylation levels in different tissues were observed. The DNA methylation levels of sperm, egg cells, two-cell embryos, morula embryos, trochophore larvae and D-shaped larvae were 13.51, 11.80, 12.14, 12.60, 14.65 and 13.18 %, respectively. Development stages of two-cell embryos, morula embryos, trochophore larvae and D-shaped larvae indicated a higher number of identical DNA methylation status loci in the egg, compared to that in the sperm. It is probable that DNA methylation patterns of the progeny are mainly influenced by the egg, while the sperm may become increasingly important during the process of early embryo development. The observed differences in methylation levels in the tissues and the development stages of P. fucata suggest that DNA methylation may act as an epigenetic regulator during tissue differentiation, individual growth, and development. [ABSTRACT FROM AUTHOR]

Pearl oysters have been found to secrete nacre and form pearls with good quality and significant commercial interest. However, the transcriptomic and genomic resources for pearl oysters are still limited. To improve this situation, transcriptome sequencing was conducted from four species of pearl oysters with Illumina HiSeq™ 2000. There were four gigabase-scale transcriptomes for four species of pearl oysters, ∼26.3 million reads with ∼2.37 gigabase base pairs (Gbp) in Pinctada fucata, ∼26.5 million reads with ∼2.39 Gbp in Pinctada margaritifera, ∼27.0 million reads with ∼2.43 Gbp in Pinctada maxima, and ∼25.9 million reads with ∼2.33 Gbp in Pteria penguin, respectively. After sequence assembly and blastx alignment, the numbers of annotated unigenes ≥200 bp were 33,882 in P. fucata, 30,666 in P. margaritifera, 26,420 in P. maxima, and 29,928 in P. penguin. Based on these annotated unigenes among four species of pearl oysters, CDSs were extracted and predicted and furthermore, analyses of GO and KEGG assignments were performed. In addition, 60 putative genes of growth factors and their receptors from four species of pearl oysters were predicted. This study established an excellent resource for gene discovery and expression in pearl oysters, but also offered a significant platform for functional genomics and comparative genomic studies for mollusks. [ABSTRACT FROM AUTHOR]

Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. We genetically labeled and manipulated MrgprA3+ neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3+ neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3+ neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3+ neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain can significantly reduce quality of life and place an economic burden on individuals and society. Spinal cord stimulation (SCS) is an alternative approach to the treatment of neuropathic pain when standard pharmacological agents have failed. However, an improved understanding of the mechanisms by which SCS inhibits pain is needed to enhance its clinical utility. This review summarizes important findings from recent studies of SCS in animal models of neuropathic pain, highlights current understanding of the spinal neurophysiological and neurochemical mechanisms by which SCS produces an analgesic effect, and discusses the potential clinical applicability of these findings and future directions for research. [ABSTRACT FROM AUTHOR]

Visfatin (also known as nicotinamide phosphoribosyltransferase and pre-B cell colony-enhancing factor) is a multifunctional protein. Visfatin has been reported to be involved in several biological processes in the cardiovascular system, . However, the role of visfatin in hypertension is still unclear. In this study, we examined the circulating and local adipose visfatin levels in spontaneously hypertensive rats (SHR), stroke-prone spontaneously hypertensive rats (SHR-SP), and in their normotensive control Wistar-Kyoto (WKY). SHR and SHR-SP rats exhibited lower body weight, lower fat tissue and hypolipidemia. No differences of serum visfatin levels were observed in SHR/SHR-SP and WKY. Serum visfatin levels did not correlate to serum glucose, lipids, insulin, and fat pad weights, but significantly correlated to weights of skeletal muscle. Visfatin expression in visceral fat tissue was slightly lower in SHR-SP compared with that in WKY. Moreover, there were no significant differences of visfatin expression in skeletal muscles among WKY, SHR and SHR-SP. Finally, visfatin protein was detected in L6 rat skeletal muscle cell culture medium, indicating that visfatin was secreted from skeletal muscle cells. Thus, our results may provide useful information for understanding the characteristic of visfatin in hypertensive models, and support the view that visfatin may be a myokine. [ABSTRACT FROM AUTHOR]

This paper proposes a time-domain clustered transmitter power adaptation scheme for orthogonal frequency division multiplexing (OFDM) system, which can significantly reduce the feedback amount during power adaptation comparison with conventional frequency-domain adaptation schemes. It was found that the cluster size plays an important role on the adaptation performance, especially for the vehicular environment. Simulation results showed that using Lagrange interpolation to obtain an explicit curve of Doppler frequency vs cluster size yields good trade-off between the resulted bit error rate (BER) and the amount of feedback. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

We applied 57Fe Mössbauer spectroscopy to sediment cores and tried to build method of estimating historical redox condition of Tokyo Bay in Japan, by using chemical state of iron as an index. As a result of measurement, there are more iron (hydr) oxide and less pyrite in sediment core sampled at Yokohama (near center of Tokyo Bay) than sediment cores sampled at inner part of the bay. This is in good agreement with water quality data and indicates that the amount of dissolved oxygen at different points can be compared by the amount of iron (hydr)oxide or pyrite. We also observed pyrite in most samples and revealed that anoxic condition had widely occurred in Tokyo Bay. In addition, a good negative correlation was found between the pyrite abundance ratio in the sediment and dissolved oxygen in seawater in summer. It was suggested that the abundance ratio of pyrite can be a quantitative indicator for the occurrence of anoxic water masses. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation was conducted to research the effect of molar ratios for α/β-HMX, γ/β-HMX, and δ/β-HMX(octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) mixture systems on thermal stability, sensitivity, and mechanical properties of explosives, and the computing models were established by Materials Studio (MS). The binding energies, the maximum trigger bond length (LN–NO2), cohesive energy density as well as mechanical properties of the mixture systems and the pure β-HMX crystal were obtained and contrasted. The results demonstrate that the molar ratios have great influence on the binding capacity of molecules between α, γ, δ-HMX, and β-HMX in the mixture systems. The binding energies decrease with the increase of molecular molar ratio and have the maximum values at the 1:1 M ratio. The maximum trigger bond length does not change apparently after mixing, while the cohesive energy density (CED) increases as the molar ratio increases but are all smaller than the pure β-HMX crystal, demonstrating that the sensitivity of the mixture systems increases. The mechanical properties decrease after mixture, which illustrates that the mechanical properties of the pure crystal are superior to the mixture systems. [ABSTRACT FROM AUTHOR]

Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration. Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice. [ABSTRACT FROM AUTHOR]

Nicotinamide phosphoribosyltransferase (NAMPT) is a promising antitumor target. Novel NAMPT inhibitors with diverse chemotypes are highly desirable for development of antitumor agents. Using high throughput screening system targeting NAMPT on a chemical library of 30000 small-molecules, we found a non-fluorescent compound F671-0003 and a fluorescent compound M049-0244 with excellent in vitro activity (IC50: 85 nM and 170 nM respectively) and anti-proliferative activity against HepG2 cells. These two compounds significantly depleted cellular NAD levels. Exogenous NMN rescued their anti-proliferative activity against HepG2 cells. Structure-activity relationship study proposed a binding mode for NAMPT inhibitor F671-0003 and highlighted the importance of hydrogen bonding, hydrophobic and π-π interactions in inhibitor binding. Imaging study provided the evidence that fluorescent compound M049-0244 (3 μM) significantly stained living HepG2 cells. Cellular fluorescence was further verified to be NAMPT dependent by using RNA interference and NAMPT over expression transgenic mice. Our findings provide novel antitumor lead compounds and a 'first-in-class' fluorescent probe for imaging NAMPT. [ABSTRACT FROM AUTHOR]