Exogenous Indole-3-Acetic Acid Suppresses Rice Infection of Magnaporthe oryzae by Affecting Plant Resistance and Fungal Growth.

Auxin is an important phytohormone that regulates diverse biologic processes, including plant growth and immunity. Indole-3-acetic acid (IAA), known as one of the main forms of auxin, is able to activate plant immunity. However, it is unknown whether IAA enhances plant resistance and/or suppresses the growth of the fungal pathogen Magnaporthe oryzae. Here, we found that IAA could induce expression levels of pathogenesis-related genes to enhance disease resistance and could control the development of blast disease through inhibiting M. oryzae infection. Exogenous IAA suppressed mycelial growth and delayed spore germination by inhibiting fungal endogenous IAA biosynthesis and impairing redox homeostasis, respectively. When applied to a field test, two IAA analogues, 1-naphthaleneacetic acid and 2,4-dichlorophenoxy acetic acid, can effectively control rice blast disease. Our study advances the understanding of IAA in controlling rice blast disease through suppressing pathogen growth and enhancing plant resistance.

Characteristics and effects on daily lives of pelvic girdle pain during early postpartum in Beijing women, China.

Pelvic girdle pain (PGP) is a common problem during pregnancy and postpartum and negatively affects women's well-being. Yet it is not well known in China. This study assessed PGP's intensity, location, and quality and the status of daily activities on postpartum women with pain, and explored the relationship between pain and the prevalence of depressive symptoms. A cross-sectional study recruiting 1,038 eligible women at 6 weeks postpartum from the obstetric clinic of a hospital was conducted in Beijing, China. Data were collected using self-reported questionnaires, including Introductory information form, Body chart, Number Rating Scale, McGill Pain Questionnaire-2, Pelvic Girdle Questionnaire, and Edinburgh Postnatal Depression Scale. In this study, 32.2 percent women experienced pain. The mean (SD) pain intensity score was 3.07 ± 1.60. About 50.6 percent women experienced sacroiliac joint pain, and 25.5 percent women experienced pain in a combination of locations. About 73.1 percent women experienced aching pain, and 57.5 percent experienced more than one kind of pain quality. The mean total score, which assesses activity and symptom limitations, was 21.93 ± 17.35 (percent), of which a normal sex life (1.29 ± 0.94) was made more challenging due to pain. In mental health, the prevalence of depressive symptoms coincided with the prevalence of pain (p = 0.008). Postpartum PGP still needs to be taken seriously, and women with pain require further support. The above knowledge offers information to manage pain, daily lives and depressive symptoms, contributes to think about strategies to better promote postpartum women physical and mental health in the future.

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury.

The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri (L. reuteri) is a well-studied probiotic that can colonize mammals including humans with known cholesterol-lowering properties and anti-inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ-aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS-stimulated bone marrow-derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage-mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.

Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS.

Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1ß, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.

Ion/Electron Co-Conductive Triple-Phase Interface Enabling Fast Redox Reaction Kinetics in Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are promising next-generation energy storage systems because of their high energy densities and high theoretical specific capacities. However, most catalysts in the LSBs are based on carbon materials, which can only improve the conductivity and are unable to accelerate lithium-ion transport. Therefore, it would be worthwhile to develop a catalytic electrode exhibiting both ion and electron conductivity. Herein, a triple-phase interface using lithium lanthanum titanate/carbon (LLTO/C) nanofibers to construct ion/electron co-conductive materials was used to afford enhanced adsorption of lithium polysulfides (LiPSs), high conductivity, and fast ion transport in working LSBs. The triple-phase interface accelerates the kinetics of the soluble LiPSs and promotes uniform Li2S precipitation/dissolution. Additionally, the LLTO/C nanofibers decrease the reaction barrier of the LiPSs, significantly improving the conversion of LiPSs to Li2S and promoting rapid conversion. Specifically, the LLTO promotes ion transport owing to its high ionic conductivity, and the carbon enhances the conductivity to improve the utilization rate of sulfur. Therefore, the LSBs with LLTO/C functional separators deliver stable life cycles, high rates, and good electrocatalytic activities. This strategy is greatly important for designing ion/electron conductivity and interface engineering, providing novel insight for the development of the LSBs.

Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Research on the classification of early-stage brain edema by combining intrinsic optical signal imaging and laser speckle contrast imaging.

The early detection and pathological classification of brain edema are very important for symptomatic treatment. The dual-optical imaging system (DOIS) consists of intrinsic optical signal imaging (IOSI) and laser speckle contrast imaging (LSCI), which can acquire cerebral hemodynamic parameters of mice in real-time, including changes of oxygenated hemoglobin concentration ( Δ C HbO 2 ), deoxyhemoglobin concentration (ΔCHbR) and relative cerebral blood flow (rCBF) within the field of view. The slope sum of Δ C HbO 2 , ΔCHbR and rCBF was proposed to classify vasogenic edema (VE) and cytotoxic edema (CE). The slope sum values in the VE and CE group remain statistically different and the classification results provide higher accuracy of more than 93% for early brain edema detection. In conclusion, the differences of hemodynamic parameters between VE and CE in the early stage were revealed and the method helps in the classification of early brain edema.

Interconnected Three-Dimensional Porous Alginate-Based Gel Electrolytes for Lithium Metal Batteries.

Lithium batteries have been widely used in our daily lives for their high energy density and long-term stability. However, their safety problems are of paramount concern for consumers, which restricts their scale applications. Gel polymer electrolytes (GPEs) compensate for the defects of liquid leakage and lower ionic conductivity of solid electrolytes, which have attracted a lot of attention. Herein, a 3D interconnected highly porous structural gel electrolyte was prepared with alginate dressing as a host material, poly(ethylene oxide) (PEO), and a commercial liquid electrolyte. With rich polar functional groups and (CH2-CH2-O) segments on the polymer matrix, the transportation of Li+ is faster and uniform; thus, the formations of lithium dendrite were significantly inhibited. The cycle stability of symmetrical Li||Li batteries with modified composite electrolytes (SAA) is greatly improved, and the overpotential remains stable after more than 1000 h. Meanwhile, under the same conditions, the cycle performance of batteries with unmodified electrolytes is inferior and overpotentials are nearly 1 V after 100 h. Additionally, the capacity retention of Li||LiFePO4 with SAA is more than 95% after 200 cycles, while those of the others declined sharply. The alginate dressing-based GPEs can greatly enhance the mechanical and thermal stability of PEO-based GPEs, which provides an environmentally friendly avenue for gel electrolytes' applications in lithium batteries.

Revisiting hemodynamics and blood oxygenation in a microfluidic microvasculature replica.

The complexity of microvascular circulation has led to the development of advanced imaging techniques and biomimetic models. This study developed a multifaceted microfluidic-based microdevice as an in vitro model of microvasculature to replicate important geometric and functional features of in vivo perfusion in mice. The microfluidic device consisted of a microchannel for blood perfusion, mirroring the natural hierarchical branching vascular structures found in mice. Additionally, the device incorporated a steady gradient of oxygen (O2) which diffused through the polydimethylsiloxane (PDMS) layer, allowing for dynamic blood oxygenation. The assembled multi-layered microdevice was accompanied by a dual-modal imaging system that combined laser speckle contrast imaging (LSCI) and intrinsic signal optical imaging (ISOI) to visualize full-field blood flow distributions and blood O2 profiles. By closely reproducing in vivo blood perfusion and oxygenation conditions, this microvasculature model, in conjunction with numerical simulation results, can provide quantitative information on physiologically relevant hemodynamics and key O2 transport parameters that are not directly measurable in traditional animal studies.

Multi-channel Small Animal Drug Metabolism Real-Time Monitoring Fluorescence System.

PURPOSE: The data acquisition of drug metabolism analysis requires a lot of time and animal resources. However, there are often many deviations in the results of pharmacokinetic analysis. Conventional methods cannot measure the blood drug concentration data in multiple tissues at the same time, and the data is obtained by in vitro measurement, which produces time errors, in vitro data errors, and individual differences between animals. In the analysis of pharmacokinetic parameters, it will seriously affect the pass rate of clinical trials of R&D drugs and the accuracy of the dosing schedule. To the best of our knowledge, we have not found the study of in vivo blood drug concentration using multi-channel equipment. Therefore, the purpose of this paper is to build a set of multi-organ monitoring and analysis instruments for synchronously monitoring the metabolism of drugs in various tissues of small animals, so as to obtain real in vivo data of blood drug concentration in real time. PROCEDURES: Using the fluorescence properties and laser-induced fluorescence principle of drugs, we designed six channels to monitor the changes of fluorescence-labeled drugs in their main metabolic organs, a multi-channel calibration method was proposed to improve the accuracy of the time-division multiplexing, the real-time collection of drug concentration in vivo is realized, and the drug metabolism curve in vivo can be observed. RESULTS: The instrument satisfies the collection of small doses of drugs such as microgram; the detection sensitivity can reach 10 ng/ml, and can monitor and collect the drug metabolism of multiple small animal tissues at the same time, which greatly reduces the use of animals, reduces the differences between individuals, and reduces consumption cost and improve the detection efficiency of parameters, and obtain data information that is closer to the real biology. CONCLUSION: The real-time continuous monitoring and data collection of the drug metabolism in the plasma of living small animals and the important organs such as kidney, liver, and spleen were realized. The research and development of new drugs and clinical research have higher practical value.

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Improving yield-related traits by editing the promoter of the heading date gene Ehd1 in rice.

KEY MESSAGE: We developed an efficient promoter editing method to create different weak Ehd1 alleles in elite japonica rice variety ZJ8 with slightly delayed heading and improved yield for use in breeding. Heading date is an important agronomic trait of rice (Oryza sativa) that determines the planting areas and cultivation seasons of different varieties, thus affecting final yield. Early heading date 1 (Ehd1) is a major rice integrator gene in the regulatory network of heading date whose expression level is negatively correlated with heading date and grain yield. Some elite japonica varieties such as Zhongjia 8 (ZJ8) show very early heading with poor agronomic traits when planted in South China. This problem can be addressed by downregulating the expression of Ehd1. In this study, we analyzed the cis-regulatory elements in the Ehd1 promoter region. We then used CRISPR/Cas9-mediated editing to modify the Ehd1 promoter at multiple target sites in ZJ8. We rapidly identified homozygous allelic mutations in the T2 generation via long-read sequencing. We obtained several Ehd1 promoter mutants with different degrees of lower Ehd1 expression, delayed heading date, and improved yield-related traits. We developed an efficient promoter editing method to create different weak Ehd1 alleles for breeding selection. Using this method, a series of heading date materials from elite varieties can be created to expand the planting area of rice and improve grain yields.

Effects of the core heading date genes Hd1, Ghd7, DTH8, and PRR37 on yield-related traits in rice.

KEY MESSAGE: We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.

Insights into brain perceptions of the different taste qualities and hedonic valence of food via scalp electroencephalogram.

Investigating brain activity is essential for exploring taste-experience related cues. The paper aimed to explore implicit (unconscious) emotional or physiological responses related to taste experiences using scalp electroencephalogram (EEG). We performed implicit measures of tastants of differing perceptual types (bitter, salty, sour and sweet) and intensities (low, medium, and high). The results showed that subjects were partially sensitive to different sensory intensities, i.e., for high intensities, taste stimuli could induce activation of different rhythm signals in the brain, with α and θ bands possibly being more sensitive to different taste types. Furthermore, the neural representations and corresponding sensory qualities (e.g., "sweet: pleasant" or "bitter: unpleasant") of different tastes could be discriminated at 250-1,500 ms after stimulus onset, and different tastes exhibited distinct temporal dynamic differences. Source localization indicated that different taste types activate brain areas associated with emotional eating, reward processing, and motivated tendencies, etc. Overall, our findings reveal a larger sophisticated taste map that accounted for the diversity of taste types in the human brain and assesses the emotion, reward, and motivated behavior represented by different tastes. This study provided basic insights and a perceptual foundation for the relationship between taste experience-related decisions and the prediction of brain activity.

Optimizing the Production of Hydrogel Microspheres Using Microfluidic Chips: The Influence of Surface Treatment on Droplet Formation Mechanism.

Microfluidic chips have been widely applied in biology and medical research for stably generating uniform droplets that can be solidified into hydrogel microspheres. However, issues such as low microsphere yield, lengthy experimental processes, and susceptibility to environmental interference need to be addressed. In this work, a simple and effective method was developed to modify microfluidic chips at room temperature to improve the production performance of hydrogel microspheres. Numerical simulation-assisted experiments were conducted to comprehensively understand the effect of solution viscosity, hydrophilicity, and flow rate ratio on droplet formation during microsphere production. Chitosan was selected as the main component and combined with poly(ethylene glycol) diacrylate to prepare photocurable hydrogel microspheres as a demonstration. As a result, grafting fluoro-silane (FOTS) increased the contact angle of the channel from 90 to approximately 110°, which led to a 12.2% increase in droplet yield. Additionally, FOTS-modification attenuated the impact of the flow rate ratio on droplet yield by 19.1%. Alternatively, depositing dopamine decreased the channel's contact angle from 90 to 60°, resulting in a 21.4% increase in particle size and enabling the chip to adjust droplet size over a wider range. Further study demonstrates that the obtained hydrogel microspheres can be modified with layers of aldehyde, which can potentially be used for controlled drug release. Overall, this study proposed a facile method for adjusting the yield and droplet size through surface treatment of microfluidic chips while also enhancing the understanding of the synergistic effects of multiple factors in microfluidics-based microsphere production.

Strategies for fertilizer management to achieve higher yields and environmental and fertilizer benefits of rice production in China.

The challenge in China is to retain high yields while lowering greenhouse gas (GHG) emissions in the context of the increasing global and Chinese demand for rice yield. Better fertilizer management is a key factor that favors intensive rice systems toward more intensive, diverse, and sustainable development to obtain higher yield and environmental benefits. Thus, we used a data-intensive approach to estimate yield, fertilizer productivity (FP) and GHG emissions based on fertilizer and soil characteristics across major Chinese rice-producing regions. The common rice production model showed medium yield, low emission intensity and FP, and low or high GHG emissions. Approximate 41 % and 10 %, 34 % and 3 %, 8 % and 2 %, and 8 % and 1 % probabilities for medium and high yield (MY and HY)-low emission intensity (LI)-low GHG emissions (LG)-high FP (HF) (MY-LI-LG-HF and HY-LI-LG-HF) were achieved in Northeast, South, Southwest, Central and East China, respectively, by adjusting basal, tillering and panicle fertilization and soil pH, N, P and K. Our results provide insights for adjusting soil nutrient traits and fertilizer inputs according to regional production potentials for higher yields and FP and lower GHG emissions in China.

MPZL2 variant analysis with whole exome sequencing in a cohort of Chinese hearing loss patients.

BACKGROUND: Hearing loss is a genetically heterogeneous disease with more than 100 genes identified. Pathogenic variants in the MPZL2 gene cause autosomal recessive non-syndromic hearing loss. MPZL2 patients showed mild to moderate progressive hearing loss with onset age around 10 years old. To date, four pathogenic variants have been identified. AIMS: To explore the clinical characteristics and variants of MPZL2-related hearing loss, and summarize the prevalence rate in overall hearing loss patients. MATERIAL AND METHODS: To determine the prevalence of MPZL2-related hearing loss in the Chinese population, we analyzed MPZL2 variants of whole exome sequencing data derived from a cohort of 385 hearing loss patients. RESULTS: Overall, homozygous MPZL2 variants were identified in 5 sporadic cases (diagnostic rate = 1.30%). A novel missense variant c.52C > T;p.Leu18Phe was identified in one other patient with compound heterozygous mutations in MPZL2, but the pathogenicity was uncertain according to the American College of Medical Genetics guidelines (2015). A patient homozygous for the c.220C > T,p.Gln74Ter variant showed congenital profound hearing loss at all frequencies, a phenotype different from previous reports. CONCLUSIONS: Our results enriched the mutation and phenotype spectrum of MPZL2-related hearing loss. Comparisons between allele frequencies of MPZL2:c.220C > T;p.Gln74Ter and other common deafness variants suggested that MPZL2:c.220C > T;p.Gln74Ter should be included in the group of common deafness variants for prescreening.

Quantitative proteomics analysis on the meat quality of processed pale, soft, and exudative (PSE)-like broiler pectoralis major by different heating methods.

This study aims to assess and compare the influences of different heating methods on the quality characteristics of pale, soft, and exudative (PSE)-like and normal (NOR) pectoralis major through quantitative proteomic analysis. A total of 632 proteins were identified, and there were 84, 89, 50, and 43 differentially abundant proteins (DAPs) between processed PSE and NOR samples after four thermal treatments, including boiling (BO), steaming (ST), roasting (RO), and microwaving (MV), respectively, where moist heating conditions led to more different protein abundance. Processed PSE muscles resulted in significant changes in structural proteins related to myofibrillar and connective tissue, which could be associated with their structural instability and degraded quality. Collagen, tropomyosin, myoglobin, and hemoglobin could be potential indicators of PSE muscles color stability and variation during thermal processing. The quantitative proteomic analysis will help correlate molecular changes with processed meat quality towards future optimization of PSE poultry meat processing.

The effect of TENS on sleep: A pilot study.

BACKGROUND: Insomnia is the second most common neuropsychiatric disorder, but the current treatments are not very effective. There is therefore an urgent need to develop better treatments. Transcutaneous electrical nerve stimulation (TENS) may be a promising means of treating insomnia. OBJECTIVE: This work aims to explore whether and how TENS modulate sleep and the effect of stimulation waveforms on sleep. METHODS: Forty-five healthy subjects participated in this study. Electroencephalography (EEG) data were recorded before and after four mode low-frequency (1 Hz) TENS with different waveforms, which were formed by superimposing sine waves of different high frequencies (60-210 Hz) and low frequencies (1-6 Hz). The four waveform modes are formed by combining sine waves of varying frequencies. Mode 1 (M1) consists of a combination of high frequencies (60-110 Hz) and low frequencies (1-6 Hz). Mode 2 (M2) is made up of high frequencies (60-210 Hz) and low frequencies (1-6 Hz). Mode 3 (M3) consists of high frequencies (110-160 Hz) and low frequencies (1-6 Hz), while mode 4 (M4) is composed of high frequencies (160-210 Hz) and low frequencies (1-6 Hz). For M1, M3 and M4, the high frequency portions of the stimulus waveforms account for 50%, while for M2, the high frequency portion of the waveform accounts for 65%. For each mode, the current intensities ranged from 4 mA to 7 mA, with values for each participant adjusted according to individual tolerance. During stimulation, the subjects were stimulated at the greater occipital nerve by the four mode TENS. RESULTS: M1, M3, and M4 slowed down the frequency of neural activity, broadened the distribution of theta waves, and caused a decrease in activity in wakefulness-related regions and an increase in activity in sleep-related regions. However, M2 has the opposite modulation effect. CONCLUSION: These results indicated that low-frequency TENS (1 Hz) may facilitate sleep in a waveform-specific manner. Our findings provide new insights into the mechanisms of sleep modulation by TENS and the design of effective insomnia treatments.

The orphan receptor Nur77 binds cytoplasmic LPS to activate the non-canonical NLRP3 inflammasome.

Intracellular sensing of lipopolysaccharide (LPS) by murine caspase-11 or human caspase-4 initiates a protease cascade, termed the non-canonical inflammasome, that results in gasdermin D (GSDMD) processing and subsequent NLRP3 inflammasome activation. In an effort aimed at identifying additional sensors for intracellular LPS by biochemical screening, we identified the nuclear orphan receptor Nur77 as an LPS-binding protein in macrophage lysates. Nr4a1-/- macrophages exhibited impaired activation of the NLRP3 inflammasome, but not caspase-11, in response to LPS. Biochemical mapping revealed that Nur77 bound LPS directly through a domain in its C terminus. Yeast two-hybrid assays identified NLRP3 as a binding partner for Nur77. The association between Nur77 and NLRP3 required the presence of LPS and dsDNA. The source of dsDNA was the mitochondria, requiring the formation of gasdermin-D pores. In vivo, Nur77 deficiency ameliorated host response to endotoxins. Thus, Nur77 functions as an intracellular LPS sensor, binding mitochondrial DNA and LPS to activate the non-canonical NLRP3 inflammasome.