MiR-184-5p represses neuropathic pain by regulating CCL1/CCR8 signaling interplay in the spinal cord in diabetic mice.

BACKGROUND: Diabetic neuropathic pain (DNP) is a serious complication for diabetic patients involving nervous system. MicroRNAs (miRNAs) are small-noncoding RNAs which are dysregulated in neuropathic pain, and might be critical molecules for pain treatment. Our previous study has shown miR-184-5p was significantly downregulated in DNP. Therefore, the mechanism of miR-184-5p in DNP was investigated in this study. METHODS: A DNP model was established through streptozotocin (STZ). The pharmacological tools were injected intrathecally, and pain behavior was evaluated by paw withdrawal mechanical thresholds (PWMTs). Bioinformatics analysis, Dual-luciferase reporter assay and fluorescence-in-situ-hybridization (FISH) were used to seek and confirm the potential target genes of miR-184-5p. The expression of relative genes and proteins was analyzed by quantitative reverse transcriptase real-time PCR (qPCR) and western blotting. RESULTS: MiR-184-5p expression was down-regulated in spinal dorsal on days 7 and 14 after STZ, while intrathecal administration of miR-184-5p agomir attenuates neuropathic pain induced by DNP and intrathecal miR-184-5p antagomir induces pain behaviors in naïve mice. Chemokine CC motif ligand 1 (CCL1) was found to be a potential target of miR-184-5p and the protein expression of CCL1 and the mRNA expression of CCR8 were up-regulated in spinal dorsal on days 7 and 14 after STZ. The luciferase reporter assay and FISH demonstrated that CCL1 is a direct target of miR-184-5p. MiR-184-5p overexpression attenuated the expression of CCL1/CCR8 in DNP; intrathecal miR-184-5p antagomir increased the expression of CCL1/CCR8 in spinal dorsal of naïve mice. CONCLUSION: This research illustrates that miR-184-5p alleviates DNP through the inhibition of CCL1/CCR8 signaling expression.

Molecular mechanisms of artificial light at night affecting circadian rhythm disturbance.

Artificial light at night (ALAN) pollution has been regarded as a global environmental concern. More than 80% of the global population is exposed to light pollution. Exacerbating this issue, artificially lit outdoor areas are growing by 2.2% per year, while continuously lit areas have brightened by 2.2% each year due to rapid population growth and expanding urbanization. Furthermore, the increasing prevalence of night shift work and smart device usage contributes to the inescapable influence of ALAN. Studies have shown that ALAN can disrupt endogenous biological clocks, resulting in a disturbance of the circadian rhythm, which ultimately affects various physiological functions. Up until now, scholars have studied various disease mechanisms caused by ALAN that may be related to the response of the circadian system to light. This review outlines the molecular mechanisms by which ALAN causes circadian rhythm abnormalities in sleep disorders, endocrine diseases, cardiovascular disease, cancer, immune impairment, depression, anxiety and cognitive impairments.

Observation of frustrated chiral dynamics in an interacting triangular flux ladder.

Quantum matter interacting with gauge fields, an outstanding paradigm in modern physics, underlies the description of various physical systems. Engineering artificial gauge fields in ultracold atoms offers a highly controllable access to the exotic many-body phenomena in these systems, and has stimulated intense interest. Here we implement a triangular flux ladder in the momentum space of ultracold 133Cs atoms, and study the chiral dynamics under tunable interactions. Through measurements of the site-resolved density evolutions, we reveal how the competition between interaction and flux in the frustrated triangular geometry gives rise to flux-dependent localization and biased chiral dynamics. For the latter in particular, the symmetry between the two legs is dynamically broken, which can be attributed to frustration. We then characterize typical dynamic patterns using complementary observables. Our work opens the avenue toward exploring correlated transport in frustrated geometries, where the interplay between interactions and gauge fields plays a key role.

Inhibition of SIRT1 promotes ultraviolet B induced cataract via downregulation of the KEAP1/NFE2L2 signaling pathway.

Due to continuous exposure to ultraviolet B(UVB) radiation, eye lenses are constantly subjected to oxidative stress that induces lens epithelial cell (LEC) apoptosis, which has been associated with the inactivation of Sirtuin1 (SIRT1). It is well-established that NFE2L2 has a major protective effect on UVB-induced oxidative stress and damage. However, whether UVB radiation affects oxidative/antioxidative imbalance and damages LECs by inactivating the protective NFE2L2-mediated antioxidative stress pathway through inhibition of SIRT1 is unknown. In our research, we established in vivo and in vitro UVB exposure models in Sprague Dawley rats and SRA01/04 cells, respectively, to investigate the effect of UVB radiation on the NFE2L2/ KEAP1 pathway and the role of SIRT1 in this process. The in vivo findings revealed that UVB radiation exposure decreased Sirt1 and Nfe2l2 levels, upregulated Keap1 expression, led to an oxidative/antioxidative imbalance and increased LEC apoptosis in the eye lens. Sirt1 downregulated Keap1 expression levels, but activated Nfe2l2 and its downstream target proteins. The in vitro findings showed that UVB inhibited the deacetylation of SIRT1 target proteins and increased the acetylation levels of KEAP1 and NFE2L2. We also found that UVB radiation exposure led to a significant decrease in both co-localization levels and protein interaction between SIRT1 and KEAP1. In addition, the inhibition of SIRT1 increased KEAP1 levels, inhibited the activity of NFE2L2 and decreased co- localization levels and protein interactions between NFE2L2 and KEAP1. These results suggested that UVB radiation decreased SIRT1 levels and inhibited the KEAP1/NFE2L2 pathway, thereby reducing its antioxidant effect, which might be an important mechanism of UVB-induced cataract.

Triazene-bridged energetic materials based on nitrotriazole: synthesis, characterization, and laser-ignited combustion performance.

Compared to the widely concerned azo bridges (-NN-), triazene bridges (-NN-NH-) with longer nitrogen chains are also favorable linking units leading to novel energetic materials. In this work, a new family of nitrogen-rich nitrotriazolate-based energetic compounds with a triazene bridge were synthesized and well characterized. The experimental results indicated that most of these new compounds have good thermal stabilities and low sensitivities. Among these, ammonium 5,5'-dinitro-3,3'-triazene-1,2,4-triazolate (3) and potassium 5-nitro-3,3'-triazene-1,2,4-triazolate (7) decomposed at a relatively high temperature (240.6 °C for 3 and 286.9 °C for 7). The impact sensitivities of the obtained compounds ranged from 15 J to 45 J. They also have relatively high positive heats of formation between 667.5 to 817.3 kJ mol-1. The calculated detonation pressures (P) were located between 23.7 and 34.8 GPa, and the calculated detonation velocities (D) were between 8011 and 9044 m s-1. Interestingly, ammonium 5-nitro-3,3'-triazene-1,2,4-triazolate (8) and hydroxylammonium 5-nitro-3,3'-triazene-1,2,4-triazole (10) possessed excellent laser-ignited combustion performance.

Testing universality of Feynman-Tan relation in interacting Bose gases using high-order Bragg spectra.

The Feynman-Tan relation, obtained by combining the Feynman energy relation with the Tan's two-body contact, can explain the excitation spectra of strongly interacting 39K Bose-Einstein condensate (BEC). Since the shift of excitation resonance in the Feynman-Tan relation is inversely proportional to atomic mass, the test of whether this relation is universal for other atomic systems is significant for describing the effect of interaction in strongly correlated Bose gases. Here we measure the high-momentum excitation spectra of 133Cs BEC with widely tunable interactions by using the second- and third-order Bragg spectra. We observe the backbending of frequency shift of excitation resonance with increasing interaction, and even the shift changes its sign under the strong interactions in the high-order Bragg spectra. Our finding shows good agreement with the prediction based on the Feynman-Tan relation. Our results provide significant insights for understanding the profound properties of strongly interacting Bose gases.

MiR-106b-5p Attenuates Neuropathic Pain by Regulating the P2X4 Receptor in the Spinal Cord in Mice.

The P2X4 receptor (P2X4R) can be upregulated after nerve injury, and its mediated spinal microglial activation makes a critical contribution to pathologically enhanced pain processing in the dorsal horn. Although some studies have partly clarified the mechanism underlying altered P2X4R expression, the specific mechanism is not well understood. MicroRNAs (miRNAs) are small noncoding RNAs which control gene expression by binding with their target mRNAs. Thus, in the present study, we investigated whether miRNA is involved in the pathogenesis of neuropathic pain by regulating P2X4R. Our results showed that P2X4R was upregulated in the spinal dorsal horn of mice following spared nerve injury (SNI), and 69 miRNAs (46 upregulated and 23 downregulated miRNAs) were differentially expressed (fold change > 2.0, P < 0.05). P2X4R was found to be a major target of miR-106b-5p (one of the downregulated miRNAs) using bioinformatics technology; quantitative real-time PCR analysis confirmed the change in expression of miR-106b-5p, and dual-luciferase reporter assays confirmed the correlation between them. Fluorescence in situ hybridization was used to show cell co-localization of P2X4R and miR-106b-5p in the spinal dorsal horn. Transfection with miR-106b-5p mimic into BV2 cells reversed the upregulation of P2X4R induced by lipopolysaccharide (LPS). Moreover, miR-106b-5p overexpression significantly attenuated neuropathic pain induced by SNI, with decreased expression of P2X4R mRNA and protein in the spinal dorsal horn; intrathecal miR-106b-5p antagomir induced pain behaviors, and increased expression of P2X4R in the spinal dorsal horn of naïve mice. These data suggest that miR-106b-5p can serve as an important regulator of neuropathic pain development by targeting P2X4R.

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice.

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

Atom-optically synthetic gauge fields for a noninteracting Bose gas.

Synthetic gauge fields in synthetic dimensions are now of great interest. This concept provides a convenient manner for exploring topological phases of matter. Here, we report on the first experimental realization of an atom-optically synthetic gauge field based on the synthetic momentum-state lattice of a Bose gas of 133Cs atoms, where magnetically controlled Feshbach resonance is used to tune the interacting lattice into noninteracting regime. Specifically, we engineer a noninteracting one-dimensional lattice into a two-leg ladder with tunable synthetic gauge fields. We observe the flux-dependent populations of atoms and measure the gauge field-induced chiral currents in the two legs. We also show that an inhomogeneous gauge field could control the atomic transport in the ladder. Our results lay the groundwork for using a clean noninteracting synthetic momentum-state lattice to study the gauge field-induced topological physics.

Identification of the Genome-wide Expression Patterns of Long Non-coding RNAs and mRNAs in Mice with Streptozotocin-induced Diabetic Neuropathic Pain.

Diabetic neuropathic pain (DNP), an early symptom of diabetic neuropathy, involves complex mechanisms. Long non-coding RNA (lncRNA) dysregulation contributes to the pathogenesis of various human diseases. Here, we investigated the genome-wide expression patterns of lncRNAs and genes in the spinal dorsal horn of mice with streptozotocin-induced DNP. Microarray analysis identified 1481 differentially expressed (DE) lncRNAs and 1096 DE mRNAs in DNP mice. Functional analysis showed that transforming growth factor-beta receptor binding was the most significant molecular function and retrograde endocannabinoid signaling was the most significant pathway of DE mRNAs. Calcium ion transport was the second most significant biological process of DE lncRNAs. Finally, we found 289 neighboring and 57 overlapping lncRNA-mRNA pairs, including ENSMUST00000150952-Mbp and AK081017-Usp15, which may be involved in DNP pathogenesis. Microarray data were validated through quantitative PCR of selected lncRNAs and mRNAs. These results suggest that aberrant expression of lncRNAs may contribute to the pathogenesis of DNP.

Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a pilot study.

BACKGROUND: The pathogenesis of autism spectrum disorders remains elusive and currently there are no diagnostic or predictive biomarkers in autism available. Proteomic profiling has been used in a wide range of neurodevelopmental disorder studies, which could produce deeper perceptions of the molecular bases behind certain disease and potentially becomes useful in discovering biomarkers in autism spectrum disorders. METHODS: Serum samples were collected from autistic children about 3 years old in age (n = 32) and healthy controls (n = 20) in similar age and gender. The samples were identified specific proteins that are differentially expressed by magnetic bead-based pre-fractionation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS). RESULTS: Eight protein peaks were significantly different in autistic children from the healthy controls (P < 0.0001). The two peaks with the most significant differences were 6428 and 7758 Da in size. CONCLUSION: According to differences in serum protein profiles between the autistic children and healthy controls, this study identified a set of differentially expressed proteins those are significant for further evaluation and might function as biomarkers in autism.

LncRNA expression in the spinal cord modulated by minocycline in a mouse model of spared nerve injury.

Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs), which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain. The abundance levels of 183 lncRNAs and 102 mRNAs were significantly modulated by both SNI and administration of minocycline. A quantitative real-time polymerase chain reaction analysis validated expression changes in three lncRNAs (NR_015491, ENSMUST00000174263, and ENSMUST00000146263). Class distribution analysis of differentially expressed lncRNAs revealed intergenic lncRNAs as the largest category. Functional analysis indicated that SNI-induced gene regulations might be involved in the activities of cytokines (IL17A and IL17F) and chemokines (CCL2, CCL5, and CCL7), whereas minocycline might exert a pain-alleviating effect on mice through actin binding, thereby regulating nociception by controlling the cytoskeleton. Thus, lncRNAs might be responsible for SNI-induced neuropathic pain and the attenuation caused by minocycline. Our study could implicate lncRNAs as potential targets for future treatment of neuropathic pain.

[Effects of irrigation using dairy effluent on grain yield, phosphorus utilization and distribu- tion in soil profile in winter wheat-summer maize rotation system].

Field experiments of winter wheat-summer maize rotation were conducted in North China Plain irrigation area to explore the effects of wheat season irrigation with dairy effluent on grain yield, phosphorus uptake, accumulative phosphorus usage efficiency and phosphorus accumulation in soil. The results showed that the irrigation with dairy effluent significantly improved the yields of winter wheat and summer maize. With the increasing of P2O5 carried by dairy effluent into soil, winter wheat yield increased at first and then decreased. When the P2O5 increased 137 kg · hm(-2), winter wheat yield increased to the maximum (7646.4 kg · hm(-2)) and the phosphorus utilization rate was the highest (24.8%). But excessive phosphorus decreased the winter wheat yield and phosphorus utilization efficiency. Summer maize yield and phosphorus uptake increased with the increase of P2O5 carried by dairy effluent. The summer maize yield increased by 2222.4-2628.6 kg · hm(-2) and the phosphorus uptake increased by 13.9-21.1 kg · hm(-2) in contrast to the control (CK). Under conventional phosphorus fertilization at 88 kg · hm(-2), and the summer maize yield increased by 2235.0 kg · hm(-2) compared with CK. As the time of irrigation with dairy effluent increasing, the grain yield increased more significantly. The cumulative phosphorus utilization in this rotation system increased year by year. After six seasons of crop harvest, the cumulative phosphorus utilization rate increased into 40.0%-47.7%. Under the experimental condition, two times of irrigation with the dairy effluents in the winter wheat-summer maize rotation system was the best operating mode.

Effect of thimerosal on the neurodevelopment of premature rats.

BACKGROUND: This study was undertaken to determine the effect of thimerosal on the neurodevelopment of premature rats. METHODS: Thimerosal was injected into premature SD rats at a dose of 32.8, 65.6, 98.4 or 131.2 µg/kg on postnatal day 1. Expression of dopamine D4 receptor (DRD4) and serotonin 2A receptor (5-HT2AR), apoptosis in the prefrontal cortex on post-injection day 49, and learning and memory function were studied and compared with those in a control group injected with saline. RESULTS: Expression of DRD4 and 5-HT2AR and learning function decreased, and apoptosis increased significantly in the 131.2 µg/kg group (P<0.001). Memory function was significantly impaired by 65.6 (P<0.05), 98.4 and 131.2 µg/kg (P<0.001). CONCLUSIONS: The negative adverse consequences on neurodevelopment observed in the present study are consistent with previous studies; this study raised serious concerns about adverse neurodevelopmental disorder such as autism in humans following the ongoing worldwide routine administration of thimerosalcontaining vaccines to infants.