Transauricular Vagal Nerve Stimulation at 40 Hz Inhibits Hippocampal P2X7R/NLRP3/Caspase-1 Signaling and Improves Spatial Learning and Memory in 6-Month-Old APP/PS1 Mice.

OBJECTIVES: Transauricular vagal nerve stimulation (taVNS) at 40 Hz attenuates hippocampal amyloid load in 6-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, but it is unclear whether 40-Hz taVNS can improve cognition in these mice. Moreover, the underlying mechanisms are still unclear. MATERIALS AND METHODS: 6-month-old C57BL/6 (wild type [WT]) and APP/PS1 mice were subjected to 40-Hz taVNS. Novel Object Recognition and the Morris Water Maze were used to evaluate cognition. Hippocampal amyloid-ß (Aß)1-40, Aß1-42, pro-interleukin (IL)-1ß, and pro-IL-18 were measured using enzyme-linked immunosorbent assays. Hippocampal Aß42, purinergic 2X7 receptor (P2X7R), nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, IL-1ß, and IL-18 expression were evaluated by western blotting. Histologic assessments including immunofluorescence, immunohistochemistry, Nissl staining, and Congo red staining were used to assess microglial phagocytosis, neuroprotective effects, and Aß plaque load. RESULTS: 40-Hz taVNS improved spatial memory and learning in 6-month-old APP/PS1 mice but did not affect recognition memory. There were no effects on the cognitive behaviors of 6-month-old WT mice. taVNS at 40 Hz modulated microglia; significantly decreased levels of Aß1-40, Aß1-42, pro-IL-1ß, and pro-IL-18; inhibited Aß42, P2X7R, NLRP3, Caspase-1, IL-1ß, and IL-18 expression; reduced Aß deposits; and had neuroprotective effects in the hippocampus of 6-month-old APP/PS1 mice. These changes were not observed in 6-month-old WT mice. CONCLUSION: Our results show that 40-Hz taVNS inhibits the hippocampal P2X7R/NLRP3/Caspase-1 signaling and improves spatial learning and memory in 6-month-old APP/PS1 mice.

Investigation on Long-Term Stability of Vermiculite Seals for Reversible Solid Oxide Cell.

A reversible solid oxide cell (RSOC) integrating solid oxide fuel (SOFC) and a solid oxide electrolysis cell (SOEC) usually utilizes compressive seals. In this work, the vermiculite seals of various thickness and compressive load during thermal cycles and long-term operation were investigated. The leakage rates of seals were gradually increased with increasing thickness and input gas pressure. The thinner seals had good sealing performance. The compressive load was carried out at thinner seals, the possible holes were squeezed, and finally the leakage rates were lower. With a fixed input gas pressure of 1 psi, 2 psi, and 3 psi, the leakage rates of 0.50 mm vermiculite remained at around 0.009 sccm/cm, 0.017 sccm/cm and 0.028 sccm/cm during twenty thermal cycles, while the leakage rates remained at around 0.011 sccm/cm for about 240 h. Simultaneously, elemental diffusions between seals and components were limited, implying good compatibility. Furthermore, the open circuit voltage (OCV) remained at around 1.04 V during 17 thermal cycles, which is close to Nernst potentials. The stack performance confirmed that the vermiculite seals can meet the structural support and sealing requirements. Therefore, the vermiculite shows good promise for application in stacks during thermal cycles and long-term operation.

LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a leading and fatal malignancy within the gastrointestinal tract. Recent advancements highlight the pivotal role of long non-coding RNAs (lncRNAs) in diverse biological pathways and pathologies, particularly in tumorigenesis. LINC01134, a particular lncRNA, has attracted considerable attention due to its oncogenic potential in hepatoma. Current research underscores LINC01134's potential in augmenting the onset and progression of HCC, with notable implications in drug resistance. This review comprehensively explores the molecular functions and regulatory mechanisms of LINC01134 in HCC, offering a fresh perspective for therapeutic interventions. By delving into LINC01134's multifaceted roles, we aim to foster novel strategies in HCC management.

Numerical investigation of atmospheric pressure plasma jet under nonuniform electric field.

With the advancement in the understanding of plasma discontinuous structures and the progress of related research, numerical methods for simulating plasmas based on continuous medium approach have encountered significant challenges. In this paper, a numerical model is presented to simulate the motion trajectory of an atmospheric pressure plasma jet under an external nonuniform electric field. The method proposes to treat the plasma jet as equivalent particles with permittivity and conductivity, based on its dielectric properties and motion characteristics. The numerical model demonstrates short calculation times and excellent agreement between simulation results and experimental observations, validating its high efficiency and effectiveness. This work contributes to a deeper understanding of the collective effect of the plasma jet and provides an effective and efficient method for predicting the motion trajectory of the plasma jet, along with guidelines for controlling plasma using external nonuniform electric fields.

Transcutaneous auricular vagal nerve stimulation inhibits limbic-regional P2X7R expression and reverses depressive-like behaviors in Zucker diabetic fatty rats.

Zucker diabetic fatty (ZDF) rats develop type 2 diabetes (T2D) along with depressive-like behaviors. Transcutaneous auricular vagal nerve stimulation (taVNS) has antidiabetic and antidepressant-like effects in ZDF rats; however, the underlying antidepressant-like mechanisms are unclear. The purinergic receptor P2X7R, which is related to inflammation and depression, is upregulated in the limbic brain regions of depressed patients and rodents and is considered as a potential therapeutic target. Thus, this study aimed to provide preliminary evidence at the molecular level of taVNS antidepressant-like effect in ZDF rats through testing their limbic-regional P2X7R expression. ZDF rats were subjected to taVNS and transcutaneous non-vagal nerve stimulation (tnVNS). Body weight and blood glucose levels were monitored weekly. Depressive-like behaviors were evaluated with the open-field test (OFT) and forced swimming test (FST). Limbic-regional P2X7R expression was examined by western blotting (WB). P2X7R expressing cells were detected by immunohistochemistry (IHC). Compared to their lean littermates (ZL rats), ZDF rats developed obesity, hyperglycemia, and depressive-like behaviors with elevated limbic-regional P2X7R expression. taVNS but not tnVNS lowered body weight, reduced and stabilized blood glucose levels, suppressed limbic-regional P2X7R expression, and reversed the depressive-like behaviors. P2X7R was found primarily expressed in ZDF rats' limbic-regional astrocytes. In conclusion, taVNS inhibits ZDF rats' limbic-regional P2X7R expression, which may be one of the taVNS antidepressant-like mechanisms.

RNA-seq analysis of antibacterial mechanism of Cinnamomum camphora essential oil against Escherichia coli.

BACKGROUND: Transcriptome analysis plays a central role in elucidating the complexity of gene expression regulation in Escherichia coli. In recent years, the overuse of antibiotics has led to an increase in antimicrobial resistance, which greatly reduces the efficacy of antibacterial drugs and affects people's health. Therefore, several researchers are focused on finding other materials, which could replace or supplement antibiotic treatment. METHODS: E. coli was treated with water, acetone and Cinnamomum camphora essential oils, respectively. The antibacterial activity was assessed using the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC), the dry weight and the wet weight of the cells. To explore the antibacterial mechanism of the oil, the RNA-Seq analysis was adopted under three different treatments. Finally, the expression of related genes was verified by Quantitative PCR. RESULTS: In this study, we showed that the C. Camphora essential oil exerted a strong antibacterial effect. Our results showed that the inhibitory efficiency increased with increasing of the concentration of essential oil. RNA-seq analysis indicated that the essential oil inhibited the growth of E. coli by inhibiting the metabolism, chemotaxis, and adhesion, meanwhile, life activities were maintained by enhancing E. coli resistance reactions. These results are contributed to uncover the antimicrobial mechanisms of essential oils against E. coli, and the C. Camphora essential oil could be applied as an antibacterial agent to replace or ally with antibiotic.

Transcutaneous auricular vagal nerve stimulation inhibits hypothalamic P2Y1R expression and attenuates weight gain without decreasing food intake in Zucker diabetic fatty rats.

Zucker diabetic fatty (ZDF) rats that harbor a mutation in the leptin receptor innately develop type 2 diabetes (T2D) with obesity. Transcutaneous auricular vagal nerve stimulation (taVNS) has an antidiabetic effect in ZDF rats. However, the underlying mechanisms of the weight-gain attenuating effect in ZDF rats by taVNS is still unclear. This study aimed to assess whether the weight-gain attenuating effect of taVNS in ZDF rats is associated with changes in the central nervous system (CNS) expression of P2Y1 receptors (P2Y1R). Adult male ZDF rats were subjected to taVNS and transcutaneous non-vagal nerve stimulation (tnVNS). Their food intake and body weight were recorded daily and weekly, respectively. P2Y1R expression in the hypothalamus, amygdala, and hippocampus was evaluated by western blotting. Hypothalamic P2Y1R expressing cells were detected using immunohistochemistry. Naïve ZDF rats were much heavier (p < 0.05) than their lean littermates (ZL rats), with elevated hypothalamic P2Y1R expression (p < 0.05). Further, taVNS but not tnVNS attenuated weight gain (p < 0.05) without decreasing food intake (p > 0.05) and suppressed hypothalamic P2Y1R expression in ZDF rats (p < 0.05). Moreover, P2Y1R showed major expression in astrocytes of ZDF rats' hypothalamus. ZDF rats innately develop obesity associated with elevated hypothalamic P2Y1R expression. taVNS attenuates weight gain in ZDF rats without changes in food intake, suggesting increased energy expenditure. Whether the reduced hypothalamic P2Y1R expression in response to taVNS is mechanistically linked to the increased energy expenditure remains to be determined.

Closed-Loop Transcutaneous Auricular Vagal Nerve Stimulation: Current Situation and Future Possibilities.

Closed-loop (CL) transcutaneous auricular vagal nerve stimulation (taVNS) was officially proposed in 2020. This work firstly reviewed two existing CL-taVNS forms: motor-activated auricular vagus nerve stimulation (MAAVNS) and respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), and then proposed three future CL-taVNS systems: electroencephalography (EEG)-gated CL-taVNS, electrocardiography (ECG)-gated CL-taVNS, and subcutaneous humoral signals (SHS)-gated CL-taVNS. We also highlighted the mechanisms, targets, technical issues, and patterns of CL-taVNS. By reviewing, proposing, and highlighting, this work might draw a preliminary blueprint for the development of CL-taVNS.

Cerebral Hemodynamic Correlates of Transcutaneous Auricular Vagal Nerve Stimulation in Consciousness Restoration: An Open-Label Pilot Study.

This study aimed to preliminarily illustrate the cerebral hemodynamic correlates of transcutaneous auricular vagal nerve stimulation (taVNS) in consciousness restoration. Arterial spin labeling (ASL) was adopted with functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) changes before and after taVNS in 10 qualified patients with disorders of consciousness (DOC). Before taVNS, five patients responded to auditory stimuli (RtAS), and five did not respond to auditory stimuli (nRtAS). The RtAS DOC patients obtained favorable prognoses after the 4-week taVNS treatment, whereas the nRtAS ones did not. Simultaneously, taVNS increased CBF of multiple brain regions in the RtAS DOC patients, but hardly in the nRtAS ones. In conclusion, the preserved auditory function might be the prior key factor of the taVNS responders in DOC patients, and taVNS might alleviate RtAS DOC by activating the salience network, the limbic system, and the interoceptive system.

Influence of a nearby conductor on shape and length of a microwave plasma jet.

This Rapid Communication reports on the observation of an interesting phenomenon: the shape, especially the length, of a microwave plasma jet (MPJ) can be clearly influenced by simply placing a conductor near the plasma source, particularly when the nearby conductor is in contact with the external conductor of the coaxial microwave plasma generator, accompanied by a significant change in microwave reflection power from the terminal. To further investigate this discovery, the relationships between the length of the plume and some important factors, such as the conductivity and length of the nearby conductor, microwave input power, and gas flow velocity, are analyzed, and we find nonlinear rules of influence of these factors on the jet. Measurements of the electric potential around the jet reveal the nonuniform and non-neutral charge distribution inside the visible plasma plume, which plays a vital role in uncovering the mechanism underlying this phenomenon. The results are helpful for providing a deeper understanding of microwave plasma jet characteristics. More importantly, it provides guidelines to control the MPJ using simple structures.

Inhibition of electroacupuncture on nociceptive responses of dorsal horn neurons evoked by noxious colorectal distention in an intensity-dependent manner.

BACKGROUND: The transmission of visceral nociception can be inhibited by electroacupuncture (EA) at the spinal level. However, relationships between current intensity and EA-induced analgesia are still lacking. This study compares the effects of different intensities of EA at local acupoints and heterotopic acupoints on nociceptive responses of spinal wide dynamic range (WDR) neurons induced by noxious colorectal distension (CRD). MATERIALS AND METHODS: Experiments were conducted on 40 Sprague Dawley rats anesthetized with 10% urethane. Discharges of WDR neurons in the L1-L3 segments of the dorsal horn of the spinal cord were recorded extracellularly by glass micropipettes. Different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, 2 Hz) were applied to contralateral "Zusanli" (ST 36) or "Neiguan" (PC 6), with either the same or different segmental innervation of the colon. RESULTS: In local acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 0.5-8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 0.5-4 mA, but the inhibiting rate reached a plateau when EA exceeded 4 mA. In heterotopic acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 2-8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 2-6 mA. Further increase in the current beyond 6 mA also resulted in a plateau effect. CONCLUSION: Within a certain range, the nociceptive responses of dorsal horn neurons induced by CRD could be inhibited by EA in an intensity-dependent manner.

Electroacupuncture Inhibits Visceral Nociception via Somatovisceral Interaction at Subnucleus Reticularis Dorsalis Neurons in the Rat Medulla.

Electroacupuncture (EA) is an efficacious treatment for alleviating visceral pain, but the underlining mechanisms are not fully understood. This study investigated the role of medullary subnucleus reticularis dorsalis (SRD) neurons in the effects of EA on visceral pain. We recorded the discharges of SRD neurons extracellularly by glass micropipettes on anesthetized rats. The responses characteristics of SRD neurons to different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, and 2 Hz) on acupoints "Zusanli" (ST 36) and "Shangjuxu" (ST 37) before and during noxious colorectal distension (CRD) were analyzed. Our results indicated that SRD neurons responded to either a noxious EA stimulation ranging from 2 to 8 mA or to noxious CRD at 30 and 60 mmHg by increasing their discharge frequency at an intensity-dependent manner. However, during the stimulation of both CRD and EA, the increasing discharges of SRD neurons induced by CRD were significantly inhibited by 2-8 mA of EA. Furthermore, SRD neurons can encode the strength of EA, where a positive correlation between current intensity and the magnitude of neuronal responses to EA was observed within 2-6 mA. Yet, the responses of SRD neurons to EA stimulation reached a plateau when EA exceeded 6 mA. In addition, 0.5-1 mA of EA had no effect on CRD-induced nociceptive responses of SRD neurons. In conclusion, EA produced an inhibiting effect on visceral nociception in an intensity-dependent manner, which probably is due to the somatovisceral interaction at SRD neurons.

Bi-directional regulation of acupuncture on extrahepatic biliary system: An approach in guinea pigs.

Clinically, acupuncture affects the motility of the extrahepatic biliary tract, but the underlining mechanisms are still unknown. We applied manual acupuncture (MA) and electrical acupuncture (EA) separately at acupoints Tianshu (ST25), Qimen (LR14), Yanglingquan (GB34), and Yidan (CO11) in forty guinea pigs (4 groups) with or without atropinization under anesthesia while Sphincter of Oddi (SO) myoelectric activities and gallbladder pressure were monitored. In both MA and EA groups, stimulation at ST25 or LR14 significantly increased the frequency and amplitude of SO myoelectrical activities and simultaneously decreased the gallbladder pressure as compared to the pre-MA and pre-EA (P < 0.05). On the contrary, stimulation at GB34 or CO11 significantly decreased SO myoelectricity and increased the gallbladder pressure (P < 0.05). Pretreatment with atropine could abolish the effect of stimulation at acupoints ST25, GB34 and LR14 (P > 0.05), although significant myoelectricity increases were still inducible with MA or EA stimulation at CO11 (P < 0.05). In summary, acupuncture has bi-directional effects to gallbladder pressure and SO function, which probably due to autonomic reflex and somatovisceral interactions.

Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression.

Transcutaneous vagus nerve stimulation (tVNS), a non-invasive method of brain stimulation through the auricular branch of the vagus nerve, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism by which the effect on depression might be achieved has not been fully investigated, with only a few neuroimaging studies demonstrating tVNS-induced changes in the brains of healthy volunteers. Identifying specific neural pathways, which are influenced by tVNS compared with sham in depressed individuals, as well as determining neurobiomarkers of tVNS treatment success are needed to advance the application of tVNS for MDD. In order to address these questions, we measured fMRI brain activity of thirty-eight depressed patients assigned to undergo tVNS (n = 17) or sham (n = 21) treatment for 4 weeks, during the first stimulation session. The results showed significant fMRI signal increases in the left anterior insula, revealed by a direct comparison of tVNS and sham stimulation. Importantly, the insula activation level during the first stimulation session in the tVNS group was significantly associated with the clinical improvement at the end of the four-week treatment, as indicated by the Hamilton Depression Rating Scale (HAM-D) score. Our findings suggest that anterior insula fMRI activity could serve as a potential cortical biomarker and an early predictor of tVNS longitudinal treatment success.

[Clinical efficacy on mental retardation in the children treated with JIN's three scalp needling therapy and the training for cognitive and perceptual disturbance].

OBJECTIVE: To explore the impacts on the cognitive level of the children with mental retardation (MR) treated with JIN's three scalp needling therapy and the training for cognitive and perceptual disturbance so as to seek the more effective therapeutic method for the treatment of MR in children. Methods Sixty-six MR children were randomized into a head-point needle-retaining therapy + training group (group A) and a training after acupuncture group (group B). Seven cases and 12 cases were dropped in the two groups respectively. Twenty-six cases accomplished the treatment in the group A and 21 cases in the group B. In the group A, the points on the head were stimulated and the needles were retained (30 min after the general acupuncture, the needles on the body points were removed; and those on the head points were retained for 1 h, including Sishenzhen, Naosanzhen, Zhisanzhen and Niesanzhen). Simultaneously, the training for the cognitive perceptual disturbance was combined. In the group B, 1 h after needle retaining at the body points and head points, all the needles were removed; the training for the cognitive perceptual disturbance was followed. The treatment was given once a day, and the treatment for 3 months was required. Before and after treatment, the Wechsler intelligence scale for children (WISC) was used for evaluation and observation of verbal intelligence quotient (VIQ) , performance intelligence quotient (PIQ) and full-scale intelligence quotient (TFIQ) and score changes of 11 items such as information, picture vocabu; lary, arithmetic, picture generalization, comprehension, etc. RESULTS: After treatment, FIQ, VIQ and PIQ scores were different significantly as compared with those before treatment (all P<0. 01). In the group A, the results of picture vocabulary, animal egg laying, maze, block design and geometric figure were all improved significantly (all P<0. 05). In the group B, the results of information, comprehension, block design and geometric figure were all improved significantly (all P<0. 05). After treatment, concerning the value difference in FIQ and PIQ of the two groups; the changes in the group A were more significant (both P<0. 01). After treatment, the results of picture vocabulary and maze were improved significantly in the group A as compared with the group B (both P<. 01). The IQ categories changed apparently after treatment in the two groups, toward the higher level in tendency generally, but without significant difference (both P>0. 05). CONCLUSION: The simultaneous treatment with head point retaining of JIN's three needling therapy and the training for cognitive and perceptual disturbance obviously improves children patients' verbal comprehension, expression ability, hand-eye coordination ability, attention, logical reasoning ability and visual perception. The efficacy is better than that in the treatment of the training after acupuncture.

[Effect of acupuncture intervention on 14-3-3 expression in cerebral cortex of hypoxic-ischemic brain damage rats].

OBJECTIVE: To observe the effect of acupuncture therapy on 14-3-3, Bcl-2 and Bax expression levels in the cerebral cortex in neonatal rats with hypoxic-ischemic brain damage(HIBD). METHODS: Timed pregnant Sprague-Dawley rat dams were delivered either vaginally (normal group), or by C-section (sham-operation group) or by C-section with 5 min of global anoxia (anoxia group), with 8 rats in each group. The rat pups of the anoxia group were randomly divided into model group and acupuncture group (n =8). Acupuncture stimulation of "Naosanzhen" "Niesanzhen" and "Zhisanzhen" acupoints was given begin- ning from the 14th day after birth, once daily for 7 consecutive days. All rat pups were killed by decapitation on day 21 after birth, and then 14-3-3, Bcl-2 and Bax immunoactivity (expression) in the cerebral cortex were detected by immunohistochemistry. RESULTS: In comparison with the normal group, the expression level of cerebral cortical 14-3-3 was significantly decreased, and that of Bax remarkably increased in the model group (P<0. 01, P<0. 05). Compared to the model group, cortical 14-3-3 and Bcl-2 expression levels were markedly up-regulated in the acupuncture group (P<0.01, P<0.05). Compared to the normal group, cortical 14-3-3 expression level was obviously lower, but Bax expression level significantly higher in the sham-operation group (P<0. 05, P<0. 01). No significant differences were found between the model and normal groups in the expression levels of Bcl-2, and between the acupuncture and model groups in the expression levels of Bax (P>0. 05). CONCLUSION: Acupuncture intervention can increase the expression of 14-3-3 and Bcl-2 in the cerebral cortex in HIBD rats.

[Treatment of autism children: observation on efficacy of behavior training with retention of needles on head].

OBJECTIVE: To observe the effect difference of behavior training with head needling retention and behavior training after acupuncture for autism children. METHODS: Sixty qualified autism children were divided randomly into simultaneous head needling retention and behavior training group (trial group) and behavior training after acupuncture treatment group (control group) with 30 case in each group. Retention needles on the head with simultaneous behavior training was applied for the trial group. The main acupoints included Sishen Xue, Dingshen Sanxue (3 points for mental tranquilization), Nao Sanxue (3 points for the function of brain), Shou Zhisanxue (3 points for mental activities on hand) and Zozhi Sonxue (3 points for mental activities on foot). Other points were combined according to conditions of patients. Needles on the 4 extremities were withdrawn first after 30 minutes, needles on head were remained during behavior training. While behavior training was applied to the control group when acupuncture treatment was completely accomplished. Treatments were applied once a day to both groups. And 3 months was taken as one observation cycle. Estimation was made on therapeutic effect and developing level of autism children with CARS and PEP. RESULTS: The total effective rate of the trial group was 83.3% (25/30), better than 66.7% (20/30) of the control group (P < 0.05). The CARS scores of both groups declined after the treatment. And the score of trail group was lower than the control group (all P < 0.05). While the PEP scores of both groups increased, and the score of trail group was higher than the control group (all P < 0.05). The increasing level of scores of cognitive understanding and cognitive expression were all better than the control group (all P < 0.05). CONCLUSION: The effect of behavior training with head needle retention on autism children is better than behavior training after acupuncture treatment, especially in enhancing cognition understanding and cognition expression.