Pectin demethylation-mediated cell wall Na+ retention positively regulates salt stress tolerance in oilseed rape.

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.

Low iron ameliorates the salinity-induced growth cessation of seminal roots in wheat seedlings.

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress.

Very high-frequency, gate-tunable CrPS4 nanomechanical resonator with single mode.

Two-dimensional (2D) antiferromagnetic semiconductor chromium thiophosphate (CrPS4) has gradually become a major candidate material for low-dimensional nanoelectromechanical devices due to its remarkable structural, photoelectric characteristics and potentially magnetic properties. Here, we report the experimental study of a new few-layer CrPS4 nanomechanical resonator demonstrating excellent vibration characteristics through the laser interferometry system, including the uniqueness of resonant mode, the ability to work at the very high frequency, and gate tuning. In addition, we demonstrate that the magnetic phase transition of CrPS4 strips can be effectively detected by temperature-regulated resonant frequencies, which proves the coupling between magnetic phase and mechanical vibration. We believe that our findings will promote the further research and applications of the resonator for 2D magnetic materials in the field of optical/mechanical signal sensing and precision measurement.

Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7.

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

Analgesic effect of electroacupuncture on bone cancer pain in rat model: the role of peripheral P2X3 receptor.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

Unlocking Charge Transfer Limitations for Extreme Fast Charging of Li-Ion Batteries.

Extreme fast charging (XFC) of high-energy Li-ion batteries is a key enabler of electrified transportation. While previous studies mainly focused on improving Li ion mass transport in electrodes and electrolytes, the limitations of charge transfer across electrode-electrolyte interfaces remain underexplored. Herein we unravel how charge transfer kinetics dictates the fast rechargeability of Li-ion cells. Li ion transfer across the cathode-electrolyte interface is found to be rate-limiting during XFC, but the charge transfer energy barrier at both the cathode and anode have to be reduced simultaneously to prevent Li plating, which is achieved through electrolyte engineering. By unlocking charge transfer limitations, 184 Wh kg-1 pouch cells demonstrate stable XFC (10-min charge to 80 %) which is otherwise unachievable, and the lifetime of 245 Wh kg-1 21700 cells is quintupled during fast charging (25-min charge to 80 %).

Integrated physiological and transcriptional dissection reveals the core genes involving nutrient transport and osmoregulatory substance biosynthesis in allohexaploid wheat seedlings under salt stress.

BACKGROUND: Soil salinization has become a global problem restricting the seed yield and quality of crops, including wheat (Triticum aestivum L.). Salinity significantly alters plant morphology and severely disrupts physiological homeostasis. Salt tolerance of wheat has been widely studied whereas core ion transporters responsive to salt stress remain elusive. RESULTS: In this study, the wheat seedlings were subjected to salinity toxicity for morpho-physiological and transcriptomic analysis of wheat salt tolerance. There was a inversely proportional relationship between salt concentrations and morpho-physiological parameters. Under the condition of 100 mM NaCl, the H2O2, O2-, MDA content and membrane permeability were significantly increased whereas the chlorophyll content was markedly decreased. Under salt stress, a larger proportion of Na+ was partitioned in the roots than in the shoots, which had a lower Na+/K+ ratio and proline content. Salt stress also obviously affected the homeostasis of other cations. Genome-wide transcriptomic analysis showed that a total of 2,807 and 5,570 differentially expressed genes (DEGs) were identified in the shoots and roots, respectively. Functionality analysis showed that these DEGs were mainly enriched in the KEGG pathways related to carbon metabolism, phenylalanine, and amino acid biosynthesis, and were primarily enriched in the GO terms involving proline metabolism and redox processes. The Na+ transporter genes were upregulated under salt stress, which repressed the gene expression of the K+ transporters. Salt stress also significantly elevated the expression of the genes involved in osmoregulation substances biosynthesis, and obviously affected the expression profiling of other cation transporters. Co-expression network analysis identified TaNHX6-D5/TaNHX4-B7 and TaP5CS2-B3 potentially as core members regulating wheat salt tolerance. CONCLUSIONS: These results might help us fully understand the morpho-physiological and molecular responses of wheat seedlings to salt stress, and provide elite genetic resources for the genetic modification of wheat salt tolerance.

Multiomics reveals an essential role of long-distance translocation in regulating plant cadmium resistance and grain accumulation in allohexaploid wheat (Triticum aestivum).

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, 'ZM1860', and a Cd-sensitive cultivar, 'ZM32', selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, 'ZM1860' outperformed 'ZM32', which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that 'ZM32' had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than 'ZM1860'. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.

Genome-Scale Investigation of GARP Family Genes Reveals Their Pivotal Roles in Nutrient Stress Resistance in Allotetraploid Rapeseed.

The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed (Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR, GLK, NIGT1/HRS1/HHO, KAN, and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis-acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs. Further, 29 putative miRNAs were identified to be targeting BnaGARPs. Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.

Quantification of the Dynamic Interface Evolution in High-Efficiency Working Li-Metal Batteries.

Lithium (Li) metal has been considered a promising anode for next-generation high-energy-density batteries. However, the low reversibility and intricate Li loss hinder the widespread implementation of Li metal batteries. Herein, we quantitatively differentiate the dynamic evolution of inactive Li, and decipher the fundamental interplay among dynamic Li loss, electrolyte chemistry, and the structure of the solid electrolyte interphase (SEI). The actual dominant form in inactive Li loss is practically determined by the relative growth rates of dead Li0 and SEI Li+ because of the persistent evolution of the Li metal interface during cycling. Distinct inactive Li evolution scenarios are disclosed by ingeniously tuning the inorganic anion-derived SEI chemistry with a low amount of film-forming additive. An optimal polymeric film enabler of 1,3-dioxolane is demonstrated to derive a highly uniform multilayer SEI and decreased SEI Li+ /dead Li0 growth rates, thus achieving enhanced Li cycling reversibility.

Identifying the Critical Anion-Cation Coordination to Regulate the Electric Double Layer for an Efficient Lithium-Metal Anode Interface.

The persistent efforts to reveal the formation and evolution mechanisms of solid electrolyte interphase (SEI) are of fundamental significance for the rational regulation. In this work, through combined theoretical and experimental model investigations, we elucidate that the electric double layer (EDL) chemistry at the electrode/electrolyte interface beyond the thermodynamic stability of electrolyte components predominately controls the competitive reduction reactions during SEI construction on Li metal anode. Specifically, the negatively-charged surface of Li metal will prompt substantial cation enrichment and anion deficiency within the EDL. Necessarily, only the species participating in the solvation shell of cations could be electrostatically accumulated in proximity of Li metal surface and thereafter be preferentially reduced during sustained dynamic cycling. Incorporating multi-valent cation additives to more effectively drag the favorable anionic SEI enablers into EDL is validated as a promising strategy to upgrade the Li protection performance. The conclusions drawn herein afford deeper understandings to bridge the EDL principle, cation solvation, and SEI formation, shedding fresh light on the targeted regulation of reactive alkali metal interfaces.

Non-Solvating and Low-Dielectricity Cosolvent for Anion-Derived Solid Electrolyte Interphases in Lithium Metal Batteries.

Lithium (Li) metal anodes hold great promise for next-generation high-energy-density batteries, while the insufficient fundamental understanding of the complex solid electrolyte interphase (SEI) is the major obstacle for the full demonstration of their potential in working batteries. The characteristics of SEI highly depend on the inner solvation structure of lithium ions (Li+ ). Herein, we clarify the critical significance of cosolvent properties on both Li+ solvation structure and the SEI formation on working Li metal anodes. Non-solvating and low-dielectricity (NL) cosolvents intrinsically enhance the interaction between anion and Li+ by affording a low dielectric environment. The abundant positively charged anion-cation aggregates generated as the introduction of NL cosolvents are preferentially brought to the negatively charged Li anode surface, inducing an anion-derived inorganic-rich SEI. A solvent diagram is further built to illustrate that a solvent with both proper relative binding energy toward Li+ and dielectric constant is suitable as NL cosolvent.

Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory.

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

Glutathione S-transferase pi 1 variant and squamous cell carcinoma susceptibility: a meta-analysis of 52 case-control studies.

BACKGROUND: There are several meta-analyses on the genetic relationship between the rs1695 polymorphism within the GSTP1 (glutathione S-transferase pi 1) gene and the risk of different SCC (squamous cell carcinoma) diseases, such as ESCC (oesophageal SCC), HNSCC (head and neck SCC), LSCC (lung SCC), and SSCC (skin SCC). Nevertheless, no unified conclusions have been drawn. METHODS: Herein, an updated meta-analysis was performed to evaluate the probable impact of GSTP1 rs1695 on the susceptibility to different SCC diseases under six genetic models (allele, carrier, homozygote, heterozygote, dominant, and recessive). Three online databases, namely, PubMed, WOS (Web of Science), and Embase (Excerpta Medica Database), were searched. RESULTS: Initially, we obtained a total of 497 articles. Based on our selection criteria, we eventually included 52 case-control studies (9763 cases/15,028 controls) from 47 eligible articles. As shown in the pooling analysis, there was no difference in the risk of overall SCC disease between cases and controls [allele, Pa (P value of association test) = 0.601; carrier, Pa = 0.587; homozygote, Pa = 0.689; heterozygote, Pa = 0.167; dominant, Pa = 0.289; dominant, Pa = 0.548]. Similar results were obtained after stratification by race (Asian/Caucasian), genotyping, control source, and disease type (ESCC/HNSCC/LSCC/SSCC) (all Pa > 0.05). CONCLUSION: The rs1695 polymorphism within the GSTP1 gene is not associated with the risk of overall SCC or a specific SCC type, including ESCC, HNSCC, LSCC, and SSCC.

Field study of neutrality cabin temperature for Chinese passenger in economy class of civil aircraft.

Cabin thermal comfort is an important factor for the competitiveness of civil aviation. It has become a hot topic in recent years. However, there are still no clear standards for the thermal comfort in the aircraft cabin. In this paper, the cabin thermal comfort of passengers in 30 flights was investigated. Both objective and subjective data were collected in order to obtain a neutrality cabin temperature, Tnc. The investigation shows that the distribution of Thermal Sensation Votes (TSVs) was approximately symmetric around the "Neutral" vote. The clothing insulation value of passengers, ICLO, was affected by the outdoor mean new effective temperature of departure city, ET*. Tnc also changed with the outdoor ET*. According to this field surveys, a linear relationship is built between Tnc and ET* as an adaptive model for the civil aircraft cabin. This adaptive model can be used as a reference to control the cabin operative temperature around the passengers. In this way, the cabin thermal comfort requirement may be satisfied for most of the passengers.

Inactivation of the Tuberomammillary Nucleus by GABAA Receptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats.

A prominent hypothesis, the "flip-flop switch" model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively. Muscimol dosed at 0.25 and 0.50 µg/side into the TMN during dark period dose-dependently increased slow wave sleep (SWS) accompanied by an increase in cortical EEG delta (0.5-4 Hz) and spindle (8.2-12 Hz) activities. In the meanwhile, wakefulness and EEG beta (12.2-30 Hz) activity were decreased significantly, while paradoxical sleep and EEG theta (4.2-8 Hz) activity were not changed. The increase of muscimol-induced SWS was because of prolonged SWS bout duration and not to an increased bout number. Muscimol (0.50 µg/side) administration 2 h after HA (0.125 µg/side) treatment during light period reversed the HA-induced wakefulness and EEG beta 2 (20.2-30 Hz) activity into SWS and EEG delta activity. These results demonstrate that the GABAergic inactivation of the TMN in freely moving rats and HA-treated rats promotes SWS and slow activity of cortical EEG, suggesting that the potential function of the GABAA receptor in the TMN is to dampen vigilant arousal.

Effect of Electroacupuncture on the NTS is modulated primarily by acupuncture point selection and stimulation frequency in normal rats.

BACKGROUND: The effect of electroacupuncture (EA) is affected by both the acupuncture point selection and the frequency of stimulation. However, little is known regarding acupuncture point and simulation frequency selection. Neuronal activation of the nucleus of the solitary tract (NTS) is one of the important targets of EA for modulating gastrointestinal function. This study investigated the effects of various combinations of EA frequencies and acupuncture points on NTS neurons. METHODS: Rats were randomly divided into normal, 2 Hz EA, 100 Hz EA and the alternate 2/100 Hz EA groups. Then rats in each group were randomly divided into the following two subgroups according to the acupuncture point: ST 36 group and ST 25 group. All the rats underwent electrode implantation surgery. Rats in all EA groups received one treatment with EA (a constant square wave at, 2 Hz,100 Hz or 2/100 Hz frequencies with intensities ranging from 1 to 2 mA), and NTS neuronal activation was recorded before and after EA treatment. Finally, to confirm the effect of EA on the NTS, minimal acupuncture was administered and its effect on NTS was detected. RESULTS: ST 36 stimulated with 2 Hz EA significantly increased the population of excited NTS neurons and spike frequency. However, ST 36 stimulated with 100 Hz or 2/100 Hz EA produced only a transient effect on the activity of NTS neurons and did not induce any effect on the spike frequency. Furthermore, the excitatory effect of 100 Hz or 2/100 Hz EA on NTS neurons in the ST 36 group was lower than 2 Hz EA at the same point. When applied to ST 25, 2 Hz EA had no significant excitatory effect on NTS neurons or spike frequency. However, 100 Hz EA or 2/100 Hz EA at ST 25 decreased both NTS neuronal excitability and spike frequency. By comparing the effects of different EA combinations, it was shown 2 Hz EA applied to ST 36 had the strongest excitatory effect on NTS neurons, while 100 Hz EA applied to ST 25 had the greatest inhibitory effect. Minimal acupuncture stimulation produced no effect on NTS neurons. CONCLUSION: EA's effects on NTS were mainly affected by the acupuncture point selection, but the frequency of EA also played a role. Different combinations of acupuncture points and frequency selection may lead to different EA effects on NTS neuronal excitability.

[Influence of exogenous ginsenosides on new forest soil microbial communities].

Ginsenosides are the main active ingredient and allelochemicals of Panax ginseng, and they play an important role in ginseng growth and in ecological adaptation. To study the influence of ginsenosides on soil microbial communities, the method of given exogenous total ginsenosides of different concentrations were used to study the influence of ginsenosides on new forest soil microbial community, evaluate the change of metabolic activity of microbial community and investigate the ecological effect of ginsenosides on soil microbial community. Results showed that, exogenous total ginsenosides promoted metabolic activity of microbial community in new forest soil at different concentrations compared with the control after 10 d and 40 d treatment. After 10 d,except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest firstly increased then decreased with increase of the total ginsenosides concentration. The Substrate richness for 0.01 g•L⁻¹ soil treatment was significantly different from that of the control. After 20 d, 30 d and 40 d, except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest increased with total ginsenosides. These results suggested that ginsenosids can change soil microbial community and microbial metabolic activity, which alter soil microbial ecology and accordingly affect the growth of ginseng with accumulation of ginsenosides in the soil.

Electroacupuncture mediates extracellular signal-regulated kinase 1/2 pathways in the spinal cord of rats with inflammatory pain.

BACKGROUND: Activation of extracellular signal-regulated kinase1/2 (ERK1/2) in dorsal horn of the spinal cord by peripheral inflammation is contributed to inflammatory pain hypersensitivity. Although electroacupuncture (EA) has been widely used to alleviate various kinds of pain, the underlying mechanism of EA analgesia requires further investigation. This study investigated the relationship between EA-induced analgesia and ERK signaling involved in pain hypersensitivity. METHODS: The rats were randomly divided into control, model, EA and sham EA groups. Inflammatory pain model was induced by injecting of 100 µl Complete Freund's adjuvant (CFA) into the plantar surface of a hind paw. Rats in the EA group were treatment with EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-2 mA) at 5.5 h, 24.5 h and 48.5 h. Paw withdrawal thresholds (PWTs) were measured before modeling and at 5 h, 6 h, 25 h and 49 h after CFA injection. Rats were killed and ipsilateral side of the lumbar spinal cords were harvested for detecting the expressions of p-ERK1/2, Elk1, COX-2, NK-1 and CREB by immunohistochemistry, real-time PCR, western blot analysis and EMSA. Finally, the analgesic effect of EA plus U0126, a MEK (ERK kinase) inhibitor, on CFA rats was examined. RESULTS: Inflammatory pain was induced in rats by hindpaw injection of CFA and significantly increased phospho-ERK1/2 positive cells and protein levels of p-ERK1/2 in the ipsilateral spinal cord dorsal horn (SCDH). CFA up-regulated of cyclooxygenase-2 (COX-2) mRNA and protein expression at 6 h after injection and neurokinin-1 receptor (NK-1) expression at 49 h post-injection, in the SCDH. EA, applied to Zusanli (ST36) and Kunlun (BL60), remarkably increased the pain thresholds of CFA injected rats, significantly suppressed ERK1/2 activation and COX-2 protein expression after a single treatment, and decreased NK-1 mRNA and protein expression at 49 h. EA decreased the DNA binding activity of cAMP response element binding protein (CREB), a downstream transcription factor of ERK1/2, at 49 h after CFA injection. Moreover, EA and U0126 synergistically inhibited CFA-induced allodynia. CONCLUSIONS: The present study suggests that EA produces analgesic effect by preventing the activation of ERK1/2-COX-2 pathway and ERK1/2-CREB-NK-1 pathway in CFA rats.

Survival analysis of PLWHA undergoing combined antiretroviral therapy: exploring long-term prognosis and influencing factors.

Introduction: The survival time of human immunodeficiency virus (HIV)-infected individuals or patients with acquired immunodeficiency syndrome (AIDS) is influenced by multiple factors. Studying survival and influential factors after antiretroviral therapy (ART) contributes to improving treatment protocols, management strategies, and prognosis for people living with HIV/AIDS (PLWHA). Methods: This retrospective cohort study collected case data and follow-up records of PLWHA who received ART in Dazu District, Chongqing City, between 2007 and 2022. Cumulative survival rates were calculated using life tables. Survival curves were plotted using the Kaplan-Meier method. Uni-variable and multivariable Cox proportional hazards models analyzed factors influencing survival. Results: The study included 5,237 PLWHA receiving ART. Within the first year of ART initiation, 146 AIDS-related deaths occurred, accounting for 29.49% (146/495) of total deaths. Cumulative survival rates at 1, 5, 10, and 15 years were 0.97, 0.90, 0.85, and 0.79, respectively. During the observation period, male patients who received ART had a 1.89 times higher risk of death compared to females (aHR, 1.89; 95%; CI, 1.50-2.37). Patients aged ≥60 years had a 3.44-fold higher risk of death than those aged <30 years (aHR, 3.44; 95% CI, 1.22-9.67). Injection drug users (aHR, 4.95; 95% CI, 2.00-12.24) had a higher risk of death than those with heterosexual (aHR, 1.60; 95% CI, 0.69-3.72) and homosexual transmission. Patients with a baseline CD4+ T lymphocyte count <200 cells/µL (aHR, 8.02; 95% CI, 4.74-13.57) and between 200 and 349 cells/µL (aHR, 2.14; 95% CI, 1.26-3.64) had a higher risk of death than those with ≥350 cells/µL. Patients with ART initiation at WHO clinical stage IV had a 2.48-fold higher risk of death than those at stage I (aHR, 2.48; 95% CI, 1.17-5.23). Conclusion: The first year following ART initiation is critical in HIV/AIDS treatment, emphasizing the need for intensified follow-up and monitoring to facilitate successful immune system reconstruction. Older age, male sex, injection drug use, baseline CD4+ T lymphocyte count <200 cells/µL, and WHO clinical stage IV are associated with an increased risk of death. Tailored treatment and management strategies should be implemented for patient populations at higher risk of mortality and with a poorer prognosis.