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Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether [N.sup.6]-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment., Introduction Chemotherapy-induced neuropathic pain (CINP) is a debilitating complication caused by damage to the peripheral nervous system by chemotherapeutic agents, including paclitaxel (1). CINP occurs in approximately 50% to 90% [...]

Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS. [ABSTRACT FROM AUTHOR]

Sensitive mid‐infrared (MIR) spectroscopy is highly demanded in various fields ranging from industrial inspection, biomedical diagnosis to astronomical observation. However, the detection sensitivity of conventional MIR spectrometers is severely limited by excessive noises for existing infrared sensors, which hinders widespread use in photon‐scarce scenarios. Here, a broadband MIR single‐photon time‐stretch spectrometer is devised and implemented based on high‐fidelity spectral upconversion and time‐correlated coincidence counting. Specifically, a nanophotonic supercontinuum illumination covering 2.4–4.2 µm is nonlinearly converted to the near‐infrared band, where low‐loss single‐mode fiber and high‐performance silicon detector can be leveraged to facilitate dispersive operation and sensitive detection, respectively. The arrival time for the dispersed upconversion photons is precisely registered with a low‐timing‐jitter photon counter, which enables us to obtain a high spectral resolution about 0.5 cm−1 under a low‐light‐level illumination down to 0.14 photons/nm/pulse. In comparison to previous MIR upconversion spectrometers, the presented time‐stretch architecture favors single‐pixel simplicity and high‐throughput acquisition for the single‐photon spectral measurement. The achieved MIR spectroscopic features of broadband spectral coverage, sub‐wavenumber resolution, single‐photon sensitivity, and room‐temperature operation would stimulate immediate applications in material and life sciences. [ABSTRACT FROM AUTHOR]

Wild tea germplasm resources have high genetic diversity and are also a high-quality source for the breeding and utilization of local tea cultivars. In this study, 26 resources of wild tea plants from Badong County, Hubei Province, were collected and the genetic diversity and population structure of wild tea plants were analyzed using SSR molecular markers with the normal tea cultivars as the control. The results are as follows: (1) 16 pairs of primers detected an average of 5.12 alleles and 3.65 effective loci in the test materials. A total of 82 alleles were amplified, with each pair of primers amplifying a range of 3-8 labeled alleles. The average Shannon diversity index was 1.378. (2) Six core primer sites were selected from 16 pairs of primers, which can effectively detect and identify 26 materials in this study. (3) UPGMA evolutionary map of individual samples could divide all 48 materials into 7 categories. Wild tea plants and cultivated tea plants could be effectively divided through SSR detection. Population genetic structure analysis suggests that 26 wild tea samples could be divided into 2 subgroups. (4) Based on biochemical components, two samples with high EGCG content and two tea germplasms suitable for making black tea were selected. Results of this research show that diversity level of wild tea resources in Badong was high, with high genetic variation within the population. This study laid a foundation for further protection, development and utilization of wild tea germplasm resources in Badong. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%–7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP‐sensitive K+ (KATP) channel openers (KCOs) can be classified as such drugs. Results: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no‐reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol‐enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no‐reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP) and sarcolemmal KATP (sarcKATP) channels, triggered free radicals' production, and kinase activation. [ABSTRACT FROM AUTHOR]