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Alfalfa ( Medicago sativa L.) is one of the most extensively cultivated forage crops globally, and its nutritional quality critically influences the productivity of dairy cows. Silage fermentation is recognized as a crucial technique for the preservation of fresh forage, ensuring the retention of its vital nutrients. However, the detailed microbial components and their functions in silage fermentation are not fully understood. This study integrated large-scale microbial culturing with high-throughput sequencing to thoroughly examine the microbial community structure in alfalfa silage and explored the potential pathways of nutritional degradation via metagenomic analysis. The findings revealed an enriched microbial diversity in silage, indicated by the identification of amplicon sequence variants. Significantly, the large-scale culturing approach recovered a considerable number of unique microbes undetectable by high-throughput sequencing. Predominant genera, such as Lactiplantibacillus , Leuconostoc , Lentilactobacillus , Weissella , and Liquorilactobacillus , were identified based on their abundance and prevalence. Additionally, genes associated with Enterobacteriaceae were discovered, which might be involved in pathways leading to the production of ammonia-N and butyric acid. Overall, this study offers a comprehensive insight into the microbial ecology of silage fermentation and provides valuable information for leveraging microbial consortia to enhance fermentation quality., Importance: Silage fermentation is a microbial-driven anaerobic process that efficiently converts various substrates into nutrients readily absorbable and metabolizable by ruminant animals. This study, integrating culturomics and metagenomics, has successfully identified core microorganisms involved in silage fermentation, including those at low abundance. This discovery is crucial for the targeted cultivation of specific microorganisms to optimize fermentation processes. Furthermore, our research has uncovered signature microorganisms that play pivotal roles in nutrient metabolism, significantly advancing our understanding of the intricate relationships between microbial communities and nutrient degradation during silage fermentation., Competing Interests: The authors declare no conflict of interest.

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1β1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC 50 = 4.40 mg/L) and Myzus persicae (LC 50 = 6.44 mg/L) but also had low toxicity to Apis mellifera . Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

Phosphors with narrow-band green emissions and high photoluminescent quantum efficiency (PLQY) are significantly required for backlighting displays with wider color gamut. In this work, two centimeter-sized manganese (II) halide single crystals TMG 2 MnCl 4 and TMG 2 MnBr 4 (TMG = 1,1,3,3-tetramethylguanidine) are synthesized, exhibiting bright narrow-band green emissions with high PLQYs up to 62% and 90%, respectively. The narrow-band green light emission is located at 520 nm with a full-width at half-maximum (FWHM) of only 57 nm. The photoluminescence mechanisms of two single crystals are elaborated. Two white-light-emitting diodes for backlighting displays (BD-WLEDs) based on them are fabricated, exhibiting the widest color gamut of 122% National Television Standards Committee (NTSC), and a luminous efficacy reached ≈93 lm W -1 with excellent luminescence stability at high temperatures. These properties indicate the potential applications of tetrahedral manganese (II) hybrids in wide-color gamut backlighting displays., (© 2023 Wiley‐VCH GmbH.)

Novel agrochemicals have been successfully developed using target-based drug design (TBDD). To discover a novel, efficient, and highly selective nicotinic insecticide candidate, we developed a unified pharmacological model using TBDD by studying the binding modes of 11 nicotinic acetylcholine receptor (nAChR) modulators with acetylcholine binding protein (AChBP) targets for the first time. This model was used to design and develop a series of 1,2,4-triazolone derivatives. Bioassays demonstrated excellent insecticidal activities against Aphis glycines of compounds 4k (LC 50 = 4.95 mg/L) and 4q (LC 50 = 3.17 mg/L), and low toxicities to Apis mellifera . Additionally, compound 4q was stably bound to Aplysia californica AChBP, which was consistent with the pharmacological model obtained via molecular docking and molecular dynamics simulations. Therefore, compound 4q could be a potential lead candidate targeting nAChR. The explicit pharmacological model of nAChR modulators with Ac -AChBP in this study may facilitate the future rational design of eco-friendly nicotinic insecticides.

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Low-dimensional organic-inorganic metal halides (LOMHs) recently have attracted much attention due to their tunable crystal structures and excellent photoelectric properties. The configuration and arrangement of organic cations in LOMHs have significant effect on the structure of inorganic frameworks and luminescence properties. In this work, we systematically explored the "spatial effect" and "hydrogen bonding effect" of organic cations on the structure and properties of LOMHs, by synthesizing three LOMHs including (N-AD)PbCl 4 , (N-AD) 2 Pb 2 Br 7, and (N-AD) 4 Pb 3 I 12 (N-AD: N-acetylethylenediamine, C 4 H 10 N 2 O). Specifically, (110)-oriented two-dimensional (N-AD)PbCl 4 and (N-AD) 2 Pb 2 Br 7 with manifest blue-white emissions, originating from the free excitons (FEs) and self-trapped excitons (STEs), respectively. The UV-pumped light-emitting diode (LED)-based on (N-AD) 2 Pb 2 Br 7 was prepared, and the highest color rendering index (CRI) and correlated color temperature (CCT) were up to 80 and 4484 K, respectively. This proves its potential application in solid-state lighting.

Organic-inorganic hybrid metal halides have attracted widespread attention due to their excellent tunability and versatility. Here, we have selected pyridinium derivatives with different substituent groups or substitution positions as the organic templating cations and obtained six 1D chain-like structures. They are divided into three types: type I (single chain), type II (double chain), and type III (triple chain), with tunable optical band gaps and emission properties. Among them, only (2,4-LD)PbBr 3 (2,4-LD = 2,4-lutidine) shows an exciton-dependent emission phenomenon, ranging from strong yellow-white to weak red-white light. By comparing its photoluminescence spectrum with that of its bromate (2,4-LD)Br, it is found that the strong yellow-white emission at 534 nm mainly came from the organic component. Furthermore, through a comparison of the fluorescence spectra and lifetimes of (2,4-LD)PbBr 3 and (2-MP)PbBr 3 (2-MP = 2-methylpyridine) with similar structures at different temperatures, we confirm that the tunable emission of (2,4-LD)PbBr 3 comes from different photoluminescent sources corresponding to organic cations and self-trapped excitons. Density functional theory calculations further reveal that (2,4-LD)PbBr 3 has a stronger interaction between organic and inorganic components compared to (2-MP)PbBr 3 . This work highlights the importance of organic templating cations in hybrid metal halides and the new functionalities associated with them.

China has long exercised environmental control through the imposition of sewage charges. The start of the environmental protection tax on January 1, 2018, means that China has entered a new phase of environmental control. Unlike many previous studies on the role of environmental taxes at the firm level, this paper examines whether environmental taxes affect pollution emissions by influencing the behavioral choices of micro-actors. This paper first reviews the Pyrrhic tax, the Porter hypothesis, and the "double dividend effect." We then construct provincial panel data for 30 provinces in China from 2012 to 2019 as a sample, use the environmental protection tax as a natural experiment to evaluate the policy of this environmental protection tax using propensity score matching and difference-in-differences model, investigate the intermediate transmission mechanism of the policy implementation, and then analyze the differences in policy effects between provinces with different levels of economic development. The increased tax burden in 2018 led to a general reduction in provincial pollution emissions in which technological innovation by various groups, including firms and universities, had a mediating role., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Visual stimuli design plays an important role in brain-computer interfaces (BCIs) based on visual evoked potentials (VEPs). Variations in stimulus parameters have been shown to affect both decoding accuracy and subjective perception experience, implying the need for a trade-off in design. In this study, we comprehensively and systematically compared various combinations of amplitude contrast and spectral content parameters in the stimulus design to quantify their impact on decoding performance and subject comfort. Specifically, three parameters were investigated: 1) contrast level, 2) temporal pattern (periodic steady-state or pseudo-random code-modulated), and 3) frequency range. We collected electroencephalogram (EEG) data and subjective perception ratings from ten subjects and evaluated the decoding accuracy and subject comfort rating for different combinations of the stimulus parameters. Our results indicate that while high-frequency steady-state VEP (SSVEP) stimuli were rated the most comfortable, they also had the lowest decoding accuracy. Conversely, low-frequency SSVEP stimuli were rated the least comfortable but had the highest decoding accuracy. Standard and high-frequency M-sequence code-modulated VEPs (c-VEPs) produced intermediates between the two. We observed a consistent trade-off relationship between decoding accuracy and subjective comfort level across all parameters. Based on our findings, we offer c-VEP as a preferable stimulus for achieving reliable decoding accuracy while maintaining a reasonable level of comfortability.

Oat ( Avena sativa L. ) is one of the most widely cultivated crops used as forage. The aim of this study was to evaluate the effects of cellulase and Lactobacillus plantarum interactions with different moisture contents on oat ensiling. Oats with three moisture contents were treated with nothing (C), cellulase (CE), lactic acid bacteria (LP), or CE+LP and ensiled for 30 and 60 days. Compared with the control, LP and CE treatments increased crude protein and lactic acid concentrations and reduced the pH and ammonia nitrogen/total nitrogen (NH 3 -N/TN) ratios of silages. The addition of CE improved lignocellulosic degradation, compared with approximately 67% (LD) and 81% moisture content (HD) ensiling, CE (CE, CE+LP) ensiling in the approximately 75% moisture content (MD) group retained higher water-soluble carbohydrate, glucose, sucrose and fructose concents. The LP and CE inoculations significantly reduced the microbial community diversity, and lower values for the observed species, ACE, Chao1, and Shannon indices compared with CK-treated samples. Additives inhibited the growth of unfavorable bacteria (such as Clostridium ) and increased the abundances of lactic acid bacteria (LAB); the maximum increases in the Lactiplantibacillus abundance were obtained in the LP- and CE+LP-treated samples, improving the microbial community structure in silage. In summary, adding LP and CE effectively improved the oat fermentation quality, and better performances in ensiling oat and lignocellulose degradation were obtained with LP and CE combinations, especially for the MD group of silages that were ensiled for 60 days. The addition of CE and LP at the appropriate moisture content might be helpful for producing high-quality oat silage, and also provide a simple and feasible method to enhance the effects of bacteria and enzymes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Zhang, Lin, Li, Wang, Yu, Sun, Cheng, Xie, Wang, Li, Chen, Yang and Zheng.)

Neonicotinoids are important insecticides for controlling aphids in agriculture. Growing research suggested that neonicotinoid insecticides are a key factor causing the decline of global pollinator insects, such as bees. Flupyrimin (FLP) is a novel nicotinic insecticide with unique biological properties and no cross-resistance, and is safe for pollinators. Using FLP as the lead compound, a series of novel compounds were designed and synthesized by replacing the amide fragment with a sulfonamideone. Their structures were confirmed by 1 H NMR, 13 C NMR and HRMS spectra. Bioassay results showed that compound 2j had good insecticidal activity against Aphis glycines with an LC 50 value of 20.93 mg/L. Meanwhile, compound 2j showed significantly lower acute oral and contact toxicity to Apis mellifera . In addition, compound 2j interacted well with the protein in insect acetylcholine binding protein (AChBP). The molecular docking on honeybee nicotinic acetylcholine receptor (nAChR) indicated that the sulfonamide group of compound 2j did not form a hydrogen bond with Arg173 of the β subunit, which conforms to the reported low bee-toxicity conformation. In general, target compound 2j can be regarded as a bee-friendly insecticide candidate.

Aims: Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease with a cancer-like phenotype. Competing endogenous RNA (ceRNA) networks extensively involve in its pathological processes. But rare ceRNA networks and profound molecular mechanisms have been revealed in PAH. The aim of this study was to illuminate the ceRNA networks in PAH., Materials and Methods: In this work, we have chosen the idiopathic PAH as an example. GSE15197 (mRNA) and GSE56914 (miRNA) from the Gene Expression Omnibus (GEO) were selected to explore key genes and novel ceRNA networks in PAH by a series of integrated bioinformatic analysis. To be more scientific, a part of pairs in identified ceRNA network were detected in hypoxia-induced HPASMCs. And the dual-luciferase assay was performed to certify the relationship between miRNAs and mRNAs., Key Findings: Totally, 311 differentially expressed genes (DEGs) were identified and functional enrichment analysis illuminated that the majority of DEGs were enriched in proliferation, anti-apoptosis, inflammation and cancer-related pathways. And 10 hub genes were determined via Cytohubba after PPI network construction. Sequentially, with stepwise reverse prediction and pan-cancer co-expression analysis from mRNA to LncRNA in TargetScan, miRNet, ENCORI (Starbase V3.0) databases, a crucially ceRNA network was identified including 14 LncRNAs, 2 miRNAs, and 3 mRNAs. Further, in hypoxia-induced HPASMCs, the alterations of mRNAs, miRNAs and LncRNAs and their relationship were in accordance with the results we identified., Significance: Consequently, the unique hub genes and ceRNA network we proposed may advance our understanding of the molecular mechanisms in PAH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: Exsomes play a significant role in increasing pathophysiological processes by delivering their content. Recently, a variety of studies have showed exosomal microRNAs (miRNAs) are involved in pulmonary hypertension (PH) notably. In this study, we found that exosomal miR-211 was overexpressed in hypoxia-induced PH rats but its intrinsic regulation was unclear. Therefore, our aim was to reveal the underlying mechanism which overexpressed exosomal miR-211 targeted in the development of PH., Methods: 18 male SD rats were randomly divided into normoxia and hypoxia group, housed in normal or hypoxic chamber for 3 weeks respectively. Then, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index(RV/(LV + S)), the percentage of medial wall area (WA%) and the percentage of medial wall thickness (WT%) were measured. Expression of miR-211 in exosomes was detected by qRT-PCR. Expression of Ca 2+ /calmodulin-dependent kinase1(CaMK1)and peroxisome proliferator-activated receptors-γ(PPAR-γ)in lung tissue were detected by Western blot(WB); After miR-211 overexpressed exosomes were injected to rats through caudal vein, mPAP, PVR, RV/(LV + S), WA% and WT% were also measured. Sequentially, hypoxia rats were injected with lentivirus riched in miR-211 inhibitor via tail vein, and PH-related indicators were measured. In vitro, after miR-211 was positively or negatively regulated in pulmonary arterial smooth muscle cell (PASMC) by plasmid transfection, proliferation of PASMC was detected by CCK8, as well as the expression of CaMK1 and PPAR- γ. Further, the relationship between CaMK1 and miR-211 was verified by Dual-Luciferase assay. And the regulatory relationship of CaMK1/PPAR- γ aixs was demonstrated in PASMC., Results: Evident increases of mPAP, PVR, RVHI, WT% and WA% were observed with hypoxia administration. And the concentration of plasma exosomes in hypoxia rats was increased and positively correlated with the above indexes. miR-211 in exosomes of PH was upregulated while the expression of CaMK1 and PPAR-γ decreased in lung tissues. Further, injection of exosomes overexpressed with miR-211 demonstrated that exosomal miR-211 aggravated PH while inhibition of miR-211 attenuated PH in rats. In vitro, overexpression of miR-211 promoted the proliferation of PASMC and inhibited expression of CaMK1 and PPAR-γ in PASMC. And Dual-luciferase assay demonstrated that CaMK1 was a downstream gene of miR-211. Plasmid transfection experiments indicated that CaMK1 can promote PPAR-γ expression., Conclusion: Exosomal miR-211 promoted PH via inhibiting CaMK1/PPAR-γ axis, promoting PASMC proliferation in rats., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

Background: Reconstruction of full thickness nasal defects usually requires different donor sites for the external skin envelope, structural elements, and internal nasal lining. In this paper we present a novel single site method for dual inner lining and skeleton repair for full thickness nasal defects with a composite nasoseptal flap and extended pedicle dissection., Methods: A 72-year-old male presented with a T4b melanoma involving the nasal dorsum and left upper lateral cartilage. Following full thickness resection, reconstruction was performed with a nasoseptal flap (NSF) with attached septal cartilage and vomer in conjunction with a paramedian forehead flap. Extended pedicle dissection into the pterygopalatine fossa allowed the NSF to fully cover the defect., Results: The nasal defect was fully corrected. There was no evidence of flap compromise or nasal valve stenosis at 1 month, 2 month, and 1 year follow-up visits., Conclusions: We present here the first successful application of a composite cartilage-osseous-mucosal NSF for multilayered nasal reconstruction. In appropriate patients, this technique may obviate the need for flaps or grafts from extranasal sources, limiting donor site morbidity.

Chimeric antigen receptor T-cell therapy (CAR-T) is a novel immunotherapy used for the treatment of refractory B-cell leukemias and lymphoma. As clinical trials continue to expand, multiple treatment toxicities have been documented. Treatment-associated toxicities are typically systemic, however, focal manifestations have been described. We present a unique case of a 55-year-old female who developed oropharyngeal and laryngeal dystonia following CAR-T therapy. This case points to a possible association between CAR-T therapy and focal head and neck dystonia. Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: We investigated whether the supply of head and neck fellowship graduates matches head and neck cancer trends., Methods: Graduates between 1997 and 2017 from the American Head and Neck Society (AHNS) and United States Otolaryngology fellowship program webpages were identified. Trends in graduates were compared with head and neck cancer incidence obtained from the Center of Disease Control., Results: Of 538 fellows, 428 were from the United States. Of fellows practicing in the United States, 24.14% were female. Most practice locations were urban (98.44%). AHNS fellowship positions from 1997 to 2017 increased by nearly 1.82 per year (P < .00001). Graduates in academic positions increased by 1.03 per year (P < .00001). Concomitantly, the age-adjusted incidence rate of oral, oropharyngeal, and laryngeal cancers decreased (P = .0115)., Conclusion: There is important geographic variability in the practice locations of Head and Neck Oncologic Surgeons in the United States and our data may be helpful in matching clinical supply and demand., (© 2020 Wiley Periodicals, Inc.)

Acute inflammation is a key feature of innate immunity that initiates clearance and repair in infected or damaged tissues. Alternatively, chronic inflammation is implicated in numerous disease processes. The contribution of neuroinflammation to the pathogenesis of neurological conditions, including infection, traumatic brain injury, and neurodegenerative diseases, has become increasingly evident. Potential drivers of such neuroinflammation include toll-like receptors (TLRs). TLRs confer a wide array of functions on different cell types in the central nervous system (CNS). Importantly, how TLR activation affects astrocyte functioning is unclear. In the present study, we examined the role of TLR2/4 signaling on various astrocyte functions (i.e., proliferation, pro-inflammatory mediator production, regulatory mechanisms, etc) by stimulating astrocytes with potent exogenous TLR2/4 agonist, bacterial lipopolysaccharide (LPS). Newborn astrocytes were derived from WT, Tnfα -/- , Il1α -/- /Il1β -/- , and Tlr2 -/- /Tlr4 -/- mice as well as Sprague Dawley rats for all in vitro studies. LPS activated mRNA expression of different pro-inflammatory cytokines and chemokines in time- and concentration-dependent manners, and upregulated the proliferation of astrocytes based on increased 3 H-thymidine update. Following LPS-mediated TLR2/4 activation, TNF-α and IL-1β self-regulated and modulated the expression of pro-inflammatory cytokines and chemokines. Polyclonal antibodies against TNF-α suppressed TLR2/4-mediated upregulation of astrocyte proliferation, supporting an autocrine/paracrine role of TNF-α on astrocyte proliferation. Astrocytes perform classical innate immune functions, which contradict the current paradigm that microglia are the main immune effector cells of the CNS. TNF-α plays a pivotal role in the LPS-upregulated astrocyte activation and proliferation, supporting their critical roles in in CNS pathogenesis.

Introduction: Spinal cord stimulation (SCS) is an established, effective method of treating chronic pain. High frequency stimulation (HFS) is an alternative SCS waveform that has been shown to alleviate pain but also necessitates more frequent recharging. The purpose of this pilot study is to evaluate efficacy of alternating conventional stimulation and HFS (termed "shuffle" stimulation) in improving SCS outcomes., Methods: Shuffle stimulation was designed to deliver conventional stimulation in upright positions with relative HFS in lying positions, automated through accelerometer technology. In this 13-week cross-over study, patients were randomized to receiving conventional and shuffle stimulation in four-week blocks. Pain outcomes and sensory testing were compared from preoperative baseline and at the conclusion of each study period., Results: Twelve patients completed this study. Two patients showed no change from baseline visual analogue scale (VAS) with either type of stimulation and were excluded from statistical analysis of pain outcomes. Mean numerical rating scale (NRS) scores assessing current pain were significantly lower in shuffle stimulation (4.0 ± 1.6) compared to conventional stimulation (5.8 ± 2.3) (p = 0.024). In the total cohort, 7 of 11 patients preferred shuffle over conventional stimulation., Conclusions: This study generated preliminary evidence showing improved NRS current pain scores in shuffle stimulation compared to conventional stimulation. More patients preferred shuffle stimulation compared to conventional stimulation. Optimizing stimulation when patients are recumbent may increase patient satisfaction and pain control. The potential advantages of shuffle stimulation may warrant further investigation., (© 2018 International Neuromodulation Society.)

Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Rapamycin, when applied immediately before or after a neurological insult, also prevents the development of spontaneous recurrent seizures (epileptogenesis) in an acquired model. In the present study, we examined the mTOR pathway in rats that had already developed chronic spontaneous seizures in a pilocarpine model. We found that mTOR is aberrantly activated in brain tissues from rats with chronic seizures. Furthermore, inhibition of mTOR by rapamycin treatment significantly reduces seizure activity. Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway., ((c) 2010 Elsevier Inc. All rights reserved.)