Electroacupuncture Alleviates Streptozotocin-Induced Diabetic Neuropathic Pain via the TRPV1-Mediated CaMKII/CREB Pathway in Rats.

Diabetic neuropathic pain (DNP) is a diabetic complication that causes severe pain and deeply impacts the quality of the sufferer's daily life. Currently, contemporary clinical treatments for DNP generally exhibit a deficiency in effectiveness. Electroacupuncture (EA) is recognized as a highly effective and safe treatment for DNP with few side effects. Regrettably, the processes via which EA alleviates DNP are still poorly characterized. Transient receptor potential vanilloid 1 (TRPV1) and phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) are overexpressed on spinal cord dorsal horn (SCDH) in DNP rats, and co-localization is observed between them. Capsazepine, a TRPV1 antagonist, effectively reduced nociceptive hypersensitivity and downregulated the overexpression of phosphorylated CaMKIIα in rats with DNP. Conversely, the CaMKII inhibitor KN-93 did not have any impact on TRPV1. EA alleviated heightened sensitivity to pain caused by nociceptive stimuli and downregulated the level of TRPV1, p-CaMKIIα, and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) in DNP rats. Intrathecal injection of capsaicin, on the other hand, reversed the above effects of EA. These findings indicated that the CaMKII/CREB pathway on SCDH is located downstream of TRPV1 and is affected by TRPV1. EA alleviates DNP through the TRPV1-mediated CaMKII/CREB pathway.

Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the vlPAG and the Analgesic and Anxiolytic Effects of EA.

Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.Significance Statement Neuropathic pain is clinically accompanied by anxiety. Both glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) and electroacupuncture (EA) have demonstrated analgesic properties. However, the efficacy of these interventions in addressing neuropathic pain and its concomitant anxiety has yet to be fully elucidated. In a mice model of spared nerve injury (SNI), we observed a decreased excitability of vlPAG CamkIIα neurons. Remarkably, EA treatment significantly enhanced the excitability of these neurons. Further, chemogenetic activation of vlPAGCamkIIα+ neurons not only resulted in analgesia but also mitigated anxiety-like behaviors in SNI mice, mirroring the effects observed with EA treatment. Conversely, inhibition of vlPAGCamkIIα+ neurons activity in naive mice reduced pain thresholds and induced anxiety-like behavior, while also negating the beneficial effects of EA. These findings provide novel insights into the mechanistic interplay between chronic neuropathic pain and anxiety, highlighting the therapeutic potential of targeting vlPAG glutamatergic neurons in these conditions.

Quercetin on the properties of rice bran oil body: Focused surface charge, oxidative stability and digestive properties.

To further enhance the stability of rice bran oil body (RBOB) emulsions, this study examined the impact of various concentrations of quercetin (QU) on the microstructure, rheological properties, oxidative stability, and digestive properties of RBOB emulsions. The results indicated that by incorporating QU concentration, the particle size of RBOB emulsions could be significantly reduced to 300 nm; QU could improve the surface hydrophobicity, the emulsifying activity index and emulsification stability index of RBOB emulsions of 550, 0.078 m2/g and 50.78 min, respectively; the storage stability of RBOB emulsions was further improved; the higher concentration of QU could delay the oxidation of RBOB emulsions, among which, the 500 µmol/L concentration inhibited the strongest effect of oil oxidation. It also improved the thermal stability of RBOB emulsions. After gastrointestinal digestion, the free fatty acids release rate of RBOB emulsions with QU addition decreased to 14.68%, and RBOB emulsions were slowly hydrolyzed. Therefore, adding QU to RBOB helps to improve its stability and delay digestion.

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis.

Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.

Study on the fire extinguishing effect of compressed nitrogen foam on 280 Ah lithium iron phosphate battery.

This study conducted experimental analyses on a 280 Ah single lithium iron phosphate battery using an independently constructed experimental platform to assess the efficacy of compressed nitrogen foam in extinguishing lithium-ion battery fires. Based on theoretical analysis, the fire-extinguishing effects of compressed nitrogen foam at different outlet pressures from foam mixture tanks were analyzed, examining factors such as battery surface temperature, flame temperature, and thermal weight loss. The results indicate that the compressed nitrogen foam can extinguish the open flame of the battery in 14 s at 0.7 MPa, with the battery's surface temperature dropping by approximately 11 % before and after the application of the extinguishing agent. Compared with other commonly used extinguishing agents, the compressed nitrogen foam demonstrates superior extinguishing efficiency, but its cooling efficiency is somewhat lower. At pressures ranging from 0.4 to 0.6 MPa, the foam displays prolonged drainage time and sustained cooling effects, rendering it more suitable for lithium-ion battery fire scenarios. To address the issue of reduced cooling performance during later stages of fire suppression by compressed nitrogen foam, an intermittent injection approach has been proposed to effectively preserve its cooling efficacy.

Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis.

Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation. CXCL5 expression was increased in ankle joints of gout arthritis model mice, whereas CXCR2 showed expression in joint-innervating sensory neurons. CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to trigger TRPA1 activation, resulting in hyperexcitability and pain. Neuronal CXCR2 coordinates with neutrophilic CXCR2 to contribute to CXCL5-induced neutrophil chemotaxis via triggering CGRP- and substance P-mediated vasodilation and plasma extravasation. Neuronal Cxcr2 deletion ameliorates joint pain, neutrophil infiltration and gait impairment in model mice. We confirmed CXCR2 expression in human dorsal root ganglion neurons and CXCL5 level upregulation in serum from male patients with gouty arthritis. Our study demonstrates CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and inflammation that expands our knowledge of immunomodulation capability of nociceptive sensory neurons.

Research on gesture recognition algorithm based on MME-P3D.

A Multiscale-Motion Embedding Pseudo-3D (MME-P3D) gesture recognition algorithm has been proposed to tackle the issues of excessive parameters and high computational complexity encountered by existing gesture recognition algorithms deployed in mobile and embedded devices. The algorithm initially takes into account the characteristics of gesture motion information, integrating the channel attention (CE) mechanism into the pseudo-3D (P3D) module, thereby constructing a P3D-C feature extraction network that can efficiently extract spatio-temporal feature information while reducing the complexity of the algorithmic model. To further enhance the understanding and learning of the global gesture movement's dynamic information, a Multiscale Motion Embedding (MME) mechanism is subsequently designed. The experimental findings reveal that the MME-P3D model achieves recognition accuracies reaching up to 91.12% and 83.06% on the self-constructed conference gesture dataset and the publicly available Chalearn 2013 dataset, respectively. In comparison with the conventional 3D convolutional neural network, the MME-P3D model demonstrates a significant advantage in terms of parameter count and computational requirements, which are reduced by as much as 82% and 83%, respectively. This effectively addresses the limitations of the original algorithms, making them more suitable for deployment on embedded and mobile devices and providing a more effective means for the practical application of hand gesture recognition technology.

Neutrophil-derived oxidative stress contributes to skin inflammation and scratching in a mouse model of allergic contact dermatitis via triggering pro-inflammatory cytokine and pruritogen production in skin.

Allergic contact dermatitis (ACD) is a common skin disease featured with skin inflammation and a mixed itch/pain sensation. The itch/pain causes the desire to scratch, affecting both physical and psychological aspects of patients. Nevertheless, the mechanisms underlying itch/pain sensation of ACD still remain elusive. Here, we found that oxidative stress and oxidation-related injury were remarkably increased in the inflamed skin of a mouse model of ACD. Reducing oxidative stress significantly attenuated itch/pain-related scratching, allokonesis and skin inflammation. RNA-Sequencing reveals oxidative stress contributes to a series of skin biological processes, including inflammation and immune response. Attenuating oxidative stress reduces overproduction of IL-1ß and IL-33, two critical cytokines involved in inflammation and pain/itch, in the inflamed skin of model mice. Exogenously injecting H2O2 into the neck skin of naïve mice triggered IL-33 overproduction in skin keratinocytes and induced scratching, which was reduced in mice deficient in IL-33 receptor ST2. ACD model mice showed remarkable neutrophil infiltration in the inflamed skin. Blocking neutrophil infiltration reduced oxidative stress and attenuated scratching and skin inflammation. Therefore, our study reveals a critical contribution of neutrophil-derived oxidative stress to skin inflammation and itch/pain-related scratching of ACD model mice via mechanisms involving the triggering of IL-33 overproduction in skin keratinocytes. Targeting skin oxidative stress may represent an effective therapy for ameliorating ACD.

Oil-in-water and oleogel-in-water emulsion encapsulate with hemp seed oil containing Δ9-tetrahydrocannabinol and cannabinol: Stability, degradation and in vitro simulation characteristics.

The present study focused on investigating the stability and in vitro simulation characteristics of oil-in-water (O/W) and oleogel-in-water (Og/W) emulsions. Compared with O/W emulsion, the Og/W emulsion exhibited superior stability, with a more evenly spread droplet distribution, and the Og/W emulsion containing 3 % hemp seed protein (HSP) showed better stability against environmental factors, including heat treatment, ionic strength, and changes in pH. Additionally, the stability of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabinol (CBN) and the in vitro digestion of hemp seed oil (HSO) were evaluated. The half-life of CBN in the Og/W emulsion was found to be 131.82 days, with a degradation rate of 0.00527. The in vitro simulation results indicated that the Og/W emulsion effectively delayed the intestinal digestion of HSO, and the bioaccessibility of Δ9-THC and CBN reached 56.0 % and 58.0 %, respectively. The study findings demonstrated that the Og/W emulsion constructed with oleogel and HSP, exhibited excellent stability.

Investigating Escherichia coli habitat transition from sediments to water in tropical urban lakes.

Background: Escherichia coli is a commonly used faecal indicator bacterium to assess the level of faecal contamination in aquatic habitats. However, extensive studies have reported that sediment acts as a natural reservoir of E. coli in the extraintestinal environment. E. coli can be released from the sediment, and this may lead to overestimating the level of faecal contamination during water quality surveillance. Thus, we aimed to investigate the effects of E. coli habitat transition from sediment to water on its abundance in the water column. Methods: This study enumerated the abundance of E. coli in the water and sediment at five urban lakes in the Kuala Lumpur-Petaling Jaya area, state of Selangor, Malaysia. We developed a novel method for measuring habitat transition rate of sediment E. coli to the water column, and evaluated the effects of habitat transition on E. coli abundance in the water column after accounting for its decay in the water column. Results: The abundance of E. coli in the sediment ranged from below detection to 12,000 cfu g-1, and was about one order higher than in the water column (1 to 2,300 cfu mL-1). The habitat transition rates ranged from 0.03 to 0.41 h-1. In contrast, the E. coli decay rates ranged from 0.02 to 0.16 h-1. In most cases (>80%), the habitat transition rates were higher than the decay rates in our study. Discussion: Our study provided a possible explanation for the persistence of E. coli in tropical lakes. To the best of our knowledge, this is the first quantitative study on habitat transition of E. coli from sediments to water column.

Combined Activity of Saponin B Isolated from Dodonaea viscosa Seeds with Pesticide Azadirachtin against the Pest Spodoptera litura.

Azadirachtin is regarded as one of the best botanical pesticides due to its broad spectrum of insecticides and low interference with natural enemies. To enhance the effect of azadirachtin and slow down the generation of resistance, the combined activity was studied. Here, we found that Dodonaea viscosa saponin B (DVSB) isolated from the seeds of Dodonaea viscosa has good combined activity with the azadirachtin. The mixture of DVSB and azadirachtin in a volume ratio of 1:4 had the strongest combined effect against Spodoptera litura, with a co-toxicity coefficient (CTC) of 212.87. DVSB exerted its combined activity by affecting the contact angle, surface tension, maximum retention and cell membrane permeability. When mixed with DVSB, the contact angle and surface tension decreased by 30.38% and 23.68%, and the maximum retention increased by 77.15%. DVSB was screened as an effective combined activity botanical compound of azadirachtin upon the control of S. litura and highlights the potential application of botanical compounds as pesticide adjuvants in the pest management.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars.