Minocycline inhibits hyperpolarization-activated currents in rat substantia gelatinosa neurons

AbstractMinocycline is a widely used glial activation inhibitor that could suppress pain-related behaviors in a number of different pain animal models, yet, its analgesic mechanisms are not fully understood. Hyperpolarization-activated cation channel-induced Ih current plays an important role in neuronal excitability and pathological pain.In this study, we investigated the possible effect of minocycline on Ih of substantia gelatinosa neuron in superficial spinal dorsal horn by using whole-cell patch-clamp recording.We found that extracellular minocycline rapidly decreases Ih amplitude in a reversible and concentration-dependent manner (IC50 = 41 μM). By contrast, intracellular minocycline had no effect. Minocycline-induced inhibition of Ih was not affected by Na+ channel blocker tetrodotoxin, glutamate-receptor antagonists (CNQX and D-APV), GABAA receptor antagonist (bicuculine methiodide), or glycine receptor antagonist (strychnine). Minocycline also caused a negative shift in the activation curve of Ih, but did not alter the reversal potential. Moreover, minocycline slowed down the inter-spike depolarizing slope and produced a robust decrease in the rate of action potential firing.Together, these results illustrate a novel cellular mechanism underlying minocycline's analgesic effect by inhibiting Ih currents of spinal dorsal horn neurons

Cell-Type Specific Distribution of T-Type Calcium Currents in Lamina II Neurons of the Rat Spinal Cord

Spinal lamina II (substantia gelatinosa, SG) neurons integrate nociceptive information from the primary afferents and are classified according to electrophysiological (tonic firing, delayed firing, single spike, initial burst, phasic firing, gap firing and reluctant firing) or morphological (islet, central, vertical, radial and unclassified) criteria. T-type calcium (Cav3) channels play an essential role in the central mechanism of pathological pain, but the electrophysiological properties and the cell-type specific distribution of T-type channels in SG neurons have not been fully elucidated. To investigate the electrophysiological and morphological features of T-type channel-expressing or -lacking neurons, voltage- and current-clamp recordings were performed on either transverse or parasagittal spinal cord slices. Recording made in transverse spinal cord slices showed that an inward current (IT) was observed in 44.5% of the SG neurons that was fully blocked by Ni2+ and TTA-A2. The amplitude of IT depended on the magnitude and the duration of hyperpolarization pre-pulse. The voltage for eliciting and maximizing IT were −70 mV and −35 mV, respectively. In addition, we found that most of the IT-expressing neurons are tonic firing neurons and exhibit more negative action potential (AP) threshold and smaller difference of AP threshold and resting membrane potential (RMP) than those neurons lacking IT. Consistently, a specific T-type calcium channel blocker TTA-P2 increased the AP threshold and enlarged the difference between AP threshold and membrane potential (Ihold = 0). Meanwhile, the morphological analysis indicated that most of the IT-expressing neurons are islet neurons. In conclusion, we identify a cell-type specific distribution and the function of T-type channels in SG neurons. These findings might provide new insights into the mechanisms underlying the contribution of T-type channels in sensory transmission

Study on spatial characteristics of gangue slurry filling mining and engineering practice

Coal gangue slurry filling and disposal of solid waste is a new coal green mining technology that conforms to the green and sustainable development of coal mines and responds to national environmental protection policies.In order to establish the basic theoretical system of slurry filling, this paper uses the methods of theoretical analysis, simulation experiment and field industrial test to reveal the law of overburden movement in slurry filling space and master the distribution characteristics of voids available for slurry filling, Clarify the function relationship of "gangue slurry goaf gap".The research shows that the "key layer of slurry filling" is the key to control the space range of slurry filling in the mining process, and the spatial evolution process of "arch beam shell" corresponds to the free accumulation area, load influence area and compaction area of slurry filling space, which directly determines the effect of gangue slurry; The porosity of the collapsed rock mass in the goaf varies along the strike and vertical direction, which satisfies the negative logarithmic function relationship.Based on this, the spatial void distribution model of slurry filling is established, and the key areas of slurry filling are pointed out; Through the ground in-situ grouting filling test, the filling characteristics of gangue slurry in goaf space are proved, and the action process of gangue slurry-gob gap has experienced three stages: initial flow, inrush flow and horizontal diffusion.The industrial practice of gangue slurry filling in the free accumulation area and load affected area of slurry filling space in Huangling No.2 well has successfully verified the feasibility of underground gangue slurry filling technology and the correctness of theory, which provides a new basis for gangue solid waste disposal and green mining

The China Wind Paradox: the role of state-owned enterprises in wind power investment versus wind curtailment

China has seen a surge in wind power installation over the past decade, and is now the world leader in installed capacity. However, wind curtailment – i.e., when the power grid frequently interrupts the power connection of installed wind capacity – has become an increasingly serious problem. But despite wind curtailment significantly jeopardizing wind power developers’ profitability in China, companies have continued to invest. This study, based on extensive interviews with decision-makers in China's Central State-Owned Enterprises (CSOEs), attempts to explain this seeming paradox. Since the majority of wind power investment in China has been made by CSOEs, previous findings of SOE studies assume that this continued investment abjures “economic rationality” due to political/policy burdens. However, this study shows that this is not necessarily accurate. CSOEs’ investment behavior also accords with market logic, as they competed fiercely over wind power sites, increasing investment scale as a rational long-term strategy of profitability. We also find that the embrace of market logic by CSOEs has resulted from recent economic and power sector reforms. For a more efficient market, policymakers must pay greater attention to the quality of competition among CSOEs.status: publishe

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

Varicella zoster virus–induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Increased thermal withdrawal latency (TWL) and decreased mechanical withdrawal threshold (MWT) were observed in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice

Thymoquinone reduces cardiac damage caused by hypercholesterolemia in apolipoprotein E-deficient mice

Abstract Background Hypercholesterolemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that thymoquinone protected rats from doxorubicin-induced cardiotoxicity and cardiac damage. The aim of this study was to investigate the possible protective effects of thymoquinone against cardiac damage in apolipoprotein E knockout (ApoE−/−) mice. Methods Eight-week-old male ApoE−/− mice were randomly divided into three groups: control group fed a normal diet (ND group), a high cholesterol diet (HD group) or HD mixed with thymoquinone (HD + TQ group). All groups were fed the different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at − 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. Results The metabolic characteristics of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP) were lower in ApoE−/−HD + TQ mice than in ApoE−/− HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression was lower in the heart tissue of ApoE−/−HD + TQ mice than in those of ApoE−/−HD mice. Furthermore, the levels of macrophages and pro-inflammatory cytokines were lower in the cardiac tissues of ApoE−/−HD + TQ mice than in those of ApoE−/−HD mice. Conclusions These results indicate that thymoquinone may provide a potential therapeutic target for cardiac damage caused by hypercholesterolemia

Bridging the global stocktake gap of climate mitigation: a framework to measure political economy progress

The purpose of the first Global Stocktake (GST), which will conclude in 2023, is to measure collective progress in climate action and enhance ambition for meeting the Paris Agreement. Realizing the transformative change necessary requires popular support, political commitment, and robust institutions. These aspects of “political economy,” which explores how interactions among actors, their interests, and underlying institutions shape political and economic outcomes, are critical. However, these dimensions are currently missing from the GST. Here, we provide an indicator framework for assessing the political economy of mitigation progress. Our framework includes 16 key indicators across the 5 dimensions of national ambition, institutional arrangements, stakeholders and interests, policy effectiveness, and public opinion, and we demonstrate its feasibility for the US, China, and India. This framework addresses a major knowledge gap in the GST and aims to be useful for researchers, stakeholders, and policymakers in the pursuit of effective climate action

Clinical efficacy of transforaminal endoscopic discectomy in the treatment of recurrent lumbar disc herniation: a single-center retrospective analysis

Abstract Purpose To investigate the clinical efficacy of transforaminal endoscopic discectomy (TED) in treating recurrent lumbar disc herniation. Methods Clinical datal of 31 patients who were hospitalized in the Department of Pain Management, First Affiliated Hospital of Nanchang University, between 2015 and 2018 due to recurrent lumbar disc herniation were collected and analyzed retrospectively. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were used to assess alterations of patients’ leg pain intensity and nerve function, respectively. The Modified MacNab criteria were used to evaluate patients’ excellent and good rates. Results Compared to clinical data before surgery, there was a significant reduction in VAS scores (P < 0.01) along with a significant improvement in JOA scores (P < 0.01) at 2 years after revision surgery. The patients’ excellent and good rates were 83.9% at the 2 years after surgery. Conclusion The TED is safe and effective in the long term and is applicable to the treatment of recurrent lumbar disc herniation

Age-Related Differences in Stepping Reactions to a Balance Perturbation: A Functional Near-Infrared Spectroscopy and Surface Electromyography Study

We sought to investigate age-related differences in stepping reactions to a sudden balance perturbation, focusing on muscle activity and cortical activation. A total of 18 older healthy adults (older group, OG) and 16 young healthy adults (young group, YG) were recruited into this study. A cable-pull instrument was used to induce a forward perturbation at the waist level among participants, who were required to take the right step to maintain their postural balance. The seven right lower-limb muscle activities during periods of compensatory postural adjustments (CPAs) were recorded by surface electromyography. At the same time, the signals of channels located in the prefrontal, temporal and parietal lobes were recorded by functional near-infrared spectroscopy (fNIRS) during the whole process. Integral electromyograms of the right peroneus muscle, gluteus medius, and lateral gastrocnemius muscles showed greater activity for the OG in the CPA periods. Two channels belonging to the right pre-frontal (PFC) and pre-motor cortex (PMC) revealed lower activation in the OG compared with the YG. These findings can help us to better understand the differences at the peripheral and central levels and may provide some suggestions for future neuromodulation techniques and other clinical treatments