Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Revealing the mechanism of the lutein protective function of epicatechin-fructan glycosylated soybean protein isolate.

Lutein possesses various physiological activities but is susceptible to light degradation, thermal degradation, and oxidative degradation. As such, protecting the activity of lutein-based products using natural extracts has become a current research. In this study, lutein was protected by complexing inulin-type fructan (ITF), soybean protein isolate (SPI), and epicatechin (EC), and the protection mechanism of epicatechin-fructan glycosylated soybean protein isolate (EC-GSPI) toward lutein was elucidated comprehensively. The results showed that the addition of EC delayed the degradation of lutein. The results of light stability experiments showed that increased EC significantly enhanced the storage time of the GSPI-Lutein system from 4 to 13 days. Additionally, the effect of EC on glycosylated soybean 7S globulin (G7S) and glycosylated soybean 11S globulin (G11S) was assessed. The light stability of G11S-Lutein and G7S-Lutein after the addition of EC was from G11S > G7S → G7S > G11S. Furthermore, the proteins purified from SPI interacted differently with EC and ITF, with soybean 7S globulin (7S) mainly interacting with EC and soybean 11S globulin (11S) mainly interacting with ITF. EC-GSPI-Lutein exhibited a good protective effect, probably due to the occurrence of hygrothermal Maillard between ITF and 11S, providing a porous structure for lutein storage. At the same time, the binding of EC to 7S significantly enhanced the antioxidant property of the solution and the stability of the protein secondary structure, thereby prolonging the storage time of lutein.

A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes.

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.

In-Plane Chemical Ordering (Mo2/3 R1/3 )2 AlB2 (R = Tb, Dy, Ho, Er, Tm, and Lu) i-MAB Phases and their Two-Dimensional Derivatives (MBene): Synthesis, Structure, Magnetic, and Supercapacitor Performance.

A family of hexagonal in-plane chemical ordering (Mo2/3 R1/3 )2 AlB2 (R = Tb, Dy, Ho, Er, Tm, and Lu) i-MAB phases are synthesized with R-3m hexagonal structure. The i-MAB phases with R = Tb to Tm are considered to have a nonlinear ferromagnetic-like coupling magnetic ground state with gradually weakened magnetocrystalline anisotropy due to variant R-R distances and 4f electrons. Their 2D derivatives (2D-MBene) with rare-earth (R) atom vacancies are obtained by chemical etching. The delamination solvent, surface functional terminations, and chemical bond of 2D-MBene can be modified by one-step nitridation in environment-friendly nitrogen instead of ammonia. A phase conversion is caused by nitridation at 973 K from 2D-MBene to Mo2 N, leading to the optimized specific capacitance of 229 F g-1 . Besides exploring more rare-earth-containing laminated boride systems, this work also demonstrates the promising application of their 2D derivatives with R vacancies in supercapacitors.

DRG afferents that mediate physiologic and pathologic mechanosensation from the distal colon.

The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.

Krause corpuscles of the genitalia are vibrotactile sensors required for normal sexual behavior.

Krause corpuscles, first discovered in the 1850s, are enigmatic sensory structures with unknown physiological properties and functions found within the genitalia and other mucocutaneous tissues. Here, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of the mouse penis and clitoris and project to a unique sensory terminal region of the spinal cord. Using in vivo electrophysiology and calcium imaging, we found that both Krause corpuscle afferent types are A-fiber rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Optogenetic activation of male Krause corpuscle afferent terminals evoked penile erection, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males as well as reduced sexual receptivity of females. Thus, Krause corpuscles, which are particularly dense in the clitoris, are vibrotactile sensors crucial for normal sexual behavior.

A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes.

Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.

Transcription factor CncC potentially regulates cytochrome P450 CYP321A1-mediated flavone tolerance in Helicoverpa armigera.

Insect P450s play crucial roles in metabolizing insecticides and toxic plant allelochemicals. In this study, our results demonstrate that Helicoverpa armigera can adapt to a lower concentration of flavone (a flavonoid phytochemical), and P450 activities and CYP321A1 transcript levels significantly increase after exposure to flavone. RNAi-mediated knockdown of CYP321A1 significantly reduced the tolerance of H. armigera larvae to flavone. In addition, the regulatory mechanisms driving CYP321A1 induction following exposure to flavone were investigated. Flavone exposure significantly increased H2O2 generation in the larval midgut. The mRNA levels of HaCncC and HaMaf-s significantly increased in the midgut of H. armigera after exposure to flavone. Knockdown of HaCncC significantly inhibited expression of flavone-induced CYP321A1 and resulted in a decrease in flavone induction of CYP321A1. HaCncC knockdown significantly reduced the tolerance of H. armigera larvae to flavone. Taken together, these results indicate that HaCncC regulates expression of the CYP321A1 gene responsible for flavone tolerance in H. armigera.

Speculation of Sphingolipids in Capsanthin by Ultra-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time-of-Flight Mass Spectrometry.

Sphingolipids are constituents of cellular membranes and play important roles in cells. As nutraceutical compounds in foods, sphingolipids have been proven to be critical for human health. Therefore, the sphingolipids content of capsanthin was established based on ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole-time-of-flight mass spectrometry. A total number of 40 sphingolipids were successfully identified, including 20 Glucosylceramides and 20 Ceramides. The predominant GlcCers contain 4-hydroxy-8-sphingenine t18:1 (8) with different structures of α-OH fatty acids. For the Cers, the main long-chain bases are 4-hydroxy-8-sphingenine t18:1 (8) and 4-hydroxysphingenine (t18:0) with different structures of α-OH or α, ß-di (OH) fatty acids.

Experimental Study on the Influence of Tool Electrode Material on Electrochemical Micromachining of 304 Stainless Steel.

Different cathode materials have different surface chemical components and machining capacities, which may finally result in different machining quality and machining efficiency of workpieces. In this paper, in order to investigate the influence of cathode materials on the electrochemical machining of thin-walled workpiece made of 304 stainless steel, five cylindrical electrodes are used as the target working cathodes of electrochemical machining to conduct experiments and research, including 45# steel, 304 stainless steel, aluminum alloy 6061, brass H62, and tungsten steel YK15. The stray current corrosion, taper, and material removal rate were used as the criteria to evaluate the drilling quality of efficiency of a thin-walled workpiece made of 304 stainless steel. The research results show that from the perspectives of stray current corrosion and taper, aluminum alloy 6061 is an optimal tool cathode, which should be used in the electrochemical machining of thin-walled workpieces made of 304 stainless steel; on the aspect of material removal rate, the 45# steel, 304 stainless steel, and aluminum alloy 6061 present close material removal rates, all of which are higher than that of brass H62 and tungsten steel YK15. Based on comprehensive consideration of both machining quality and machining efficiency, the aluminum alloy 6061 is the best option as the cathode tool in the electrochemical machining of thin-walled workpieces made of 304 stainless steel.

[Clinical efficacy and safety of Xuebijing injection on sepsis: a Meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of Xuebijing injection for treating sepsis by systematic review. METHODS: Randomized controlled trials (RCT) of relevant Xuebijing injection for sepsis were searched in PubMed, Cochrane Library, CNKI, Wanfang database, VIP database from January 2000 to July 2019. Patients in control group were given conventional treatment, while patients in experimental group were treated with Xuebijing injection combined with conventional treatment. The qualities of the included trials were evaluated according to the Cochrane bias risk assessment tool. Meta-analysis of 28-day mortality, acute physiology and chronic health evaluation II (APACHE II), white blood cell count (WBC), C-reactive protein (CRP) and safety for sepsis patients with Xuebijing injection were conducted by RevMan 5.3 software. And the funnel chart was used to evaluate the publication bias of 28-day mortality. RESULTS: Fourteen clinical studies involving 938 patients in total were enrolled, among whom 475 cases in experimental group and 463 cases in control group. Meta-analysis showed that compared with the control group, the 28-day mortality, APACHE II score, WBC and CRP of the experimental group were significantly decreased [28-day mortality: relative risk (RR) = 0.52, 95% confidence interval (95%CI) was 0.40 to 0.67, P < 0.000 01, I2 = 0%; APACHE II score: mean difference (MD) = -5.48, 95%CI was -7.52 to -3.43, P < 0.000 01, I2 = 86%; WBC: MD = -2.26, 95%CI was -3.35 to -1.17, P < 0.000 1, I2 = 87%; CRP: MD = -37.43, 95%CI was -56.70 to -18.16, P = 0.000 1, I2 = 99%]. None of the 14 literatures reported the safety of Xuebijing injection, and there were no reports of participants' withdrawnness in halfway. Funnel chart analysis showed that there was a publication bias among studies with 28-day mortality. CONCLUSIONS: Xuebijing injection can improve the clinical symptoms, significantly reduce the mortality, and has high clinical application value.

Functional Characterization of an α-Esterase Gene Associated with Malathion Detoxification in Bradysia odoriphaga.

Carboxylesterases (CarEs) are a multigene superfamily of metabolic enzymes involved in metabolic detoxification of xenobiotics. In this study, an α-esterase gene (BoαE1) was identified from Bradysia odoriphaga. Phylogenetic analysis classified BoαE1 into the α-esterase clade. Developmental expression analysis indicated that BoαE1 was significantly expressed in the second to fourth larval stages. Tissue-specific expression analysis indicated that BoαE1 was highly expressed in the larval midgut. After exposure to LC30 of malathion, the CarE activity of B. odoriphaga was induced and the transcriptional level of BoαE1 was significantly up-regulated. Silencing of BoαE1 significantly increased the susceptibility of B. odoriphaga larvae to malathion. Inhibition assays in vitro indicated that malathion significantly inhibited BoαE1 activity. GC-MS assay showed that BoαE1 possesses hydrolase activity toward malathion and participates in the detoxification of malathion. These results strongly suggest that BoαE1 plays a crucial role in detoxification of malathion in B. odoriphaga.

Influences of Electron Beam Irradiation on the Physical and Chemical Properties of Zearalenone- and Ochratoxin A-Contaminated Corn and In Vivo Toxicity Assessment.

Electron beam irradiation (EBI) has high energy, no induced radioactivity, and strong degradation capacity toward mycotoxins, such as zearalenone (ZEN) and ochratoxin A (OTA). In this study, we determined EBI's influence on the physical and chemical properties of corn contaminated with ZEN and OTA. Moreover, the toxicity of corn after EBI was assessed through a mouse experiment. Amylose content and starch crystallinity in corn decreased significantly (p < 0.05) at an irradiation dose higher than 20 kGy. Scanning electron microscopy results revealed that the starch particles of corn began to be crushed at 10 kGy. Essential and total amino acid contents in corn decreased significantly with increasing irradiation dose of EBI (p < 0.05). Feeding EBI-treated corn fodders to mice could significantly improve blood biochemical indexes. The EBI-treated group was not significantly different from the normal corn group and did not display histopathological changes of the liver. EBI treatment can influence the quality of corn to some extent and effectively lower the toxicity of ZEN and OTA in contaminated corn. The results provide a theoretical and practical basis for the processing of EBI-treated corn and its safety.

Identification and Functional Analysis of a Delta Class Glutathione S-Transferase Gene Associated with Insecticide Detoxification in Bradysia odoriphaga.

A delta class glutathione S-transferase gene (BoGSTd2) is identified from Bradysia odoriphaga for the first time. Developmental expression analysis showed that expression of BoGSTd2 is significantly higher in the fourth instar larval stage and the adult stage. Tissue-specific expression analysis found that BoGSTd2 was expressed predominantly in the midgut and Malpighian tubules in the fourth instar larvae and the abdomen of adults. Expression of BoGSTd2 was significantly upregulated following exposure to chlorpyrifos and clothianidin. In vitro inhibition and metabolic assays indicated that recombinant BoGSTd2 could not directly metabolize chlorpyrifos and clothianidin. Nevertheless, disk diffusion assays indicated that BoGSTd2 plays an important role in protection against oxidative stress. RNAi assays showed that BoGSTd2 participates in the elimination of reactive oxygen species induced by chlorpyrifos and clothianidin. These results strongly suggest that BoGSTd2 plays an important role in chlorpyrifos and clothianidin detoxification in B. odoriphaga by protecting tissues from oxidative stress induced by these insecticides.

Design of UAV Downwash Airflow Field Detection System Based on Strain Effect Principle.

Accurate measurement of the downwash flow field of plant protection unmanned aerial vehicles (UAVs) is essential for analyzing the spatial distribution of droplets. To realize on-line rapid detection of the downwash flow field of a multi-rotor UAV, a flexible polypropylene detection device based on the principle of full bridge strain effect was proposed. Its performance principle was based on the physical deformation caused by wind pressure. The Fluid Flow and Static Structural modules of ANSYS 16.0 finite element software were used to simulate one-way fluid-solid coupling interaction. The surface of the resistive strain gauge embedded in the flexible detecting structure responded well to wind speed variation, hence it was suitable for downwash airflow wind field detection. By solving the strain force on the surface of the flexible detection structure, the length and layout of the grating wire of the strain gauge on the surface of the flexible detection structure were optimized. Meanwhile at 4 m·s-1 wind speed, the output voltage at varied bridge flexible acquisition systems in the acquisition card was measured. Results indicated coefficient of variation of 3.67%, 1.63% and 1.5%, respectively, which proved the good data acquisition consistency of the system. Through calibration test, the regression equation for the relationship between output voltage and wind speed for three unique sensor signal measuring circuits was established. The determination coefficients R2 for single bridge, half bridge and full bridge circuits were 0.9885, 0.9866 and 0.9959, respectively. In conclusion, by applying the multi-rotor plant protection UAV test platform, the results indicated the maximum relative error of the wind speed at each sampling point of the system at 1.0 m altitude was below 5.61%. Simulated and measured value had an RMSE maximum error of 0.1246 m·s-1. Moreover, downwash airflow detection not only has high accuracy but also has high sensitivity. Thus, there is convenience and practicability in the plant protection offered by this approach. The rapid measurement of UAV wind field and the established two-dimensional wind field model can provide a basis for precise application of agricultural aviation.

ROR alpha protects against LPS-induced inflammation by down-regulating SIRT1/NF-kappa B pathway.

Systemic inflammatory response syndrome (SIRS) is associated with excessive inflammatory response, however, the pathophysiology of inflammation is poorly understood. The retinoid-related orphan receptor α (RORα) is a key inflammatory regulator, but the mechanisms underlying its role remain unclear. The aim of this study was to investigate how RORα was involved in the regulation of inflammatory response. Here we put forward a hypothesis that RORα might negatively regulate inflammatory response by controlling silent information regulator Sirtuin 1 (SIRT1) expression. Stimulation of macrophages in vitro with LPS and LPS administration in vivo were used to explore the function of RORα and the relationship between RORα and SIRT1. We found that the level of RORα was suppressed in macrophages stimulated with LPS and overexpression or knockdown of RORα by transfection with lentivirus or siRNAs significantly decreased or increased, respectively, the pro-inflammatory cytokines IL-1ß, TNF, IL-6 and MCP-1. Importantly, overexpression of RORα suppressed inflammation and alleviated LPS-induced organ injury in vivo. Further study showed that RORα could regulate SIRT1 expression and, consequently, affect deacetyation and nuclear translocation of nuclear factor-kappa B (NF-κB) subunit p65. Moreover, the activation of SIRT1 by its specific agonist, SR1720, could reduce the expression of proinflammatory cytokines in RORα knockdown macrophages stimulated with LPS. In conclusion, we demonstrated that RORα could alleviate LPS-induced inflammation and organ injury both in vivo and in vitro by blocking NF-κB p65 nuclear translocation and restricting acetylation of NF-κB p65 at lysine 310 via the regulation of SIRT1 expression. Targeting RORα might be a promising therapeutic strategy to regulate inflammatory disorders.

Identification of a bilirubin receptor that may mediate a component of cholestatic itch.

Various pathologic conditions result in jaundice, a yellowing of the skin due to a buildup of bilirubin. Patients with jaundice commonly report experiencing an intense non-histaminergic itch. Despite this association, the pruritogenic capacity of bilirubin itself has not been described, and no bilirubin receptor has been identified. Here, we demonstrate that pathophysiologic levels of bilirubin excite peripheral itch sensory neurons and elicit pruritus through MRGPRs, a family of G-protein coupled receptors expressed in primary sensory neurons. Bilirubin binds and activates two MRGPRs, mouse MRGPRA1 and human MRGPRX4. In two mouse models of pathologic hyperbilirubinemia, we show that genetic deletion of either Mrgpra1 or Blvra, the gene that encodes the bilirubin-producing enzyme biliverdin reductase, attenuates itch. Similarly, plasma isolated from hyperbilirubinemic patients evoked itch in wild-type animals but not Mrgpra1-/- animals. Removing bilirubin decreased the pruritogenic capacity of patient plasma. Based on these data, targeting MRGPRs is a promising strategy for alleviating jaundice-associated itch.

Impaired GABA Neural Circuits Are Critical for Fragile X Syndrome.

Fragile X syndrome (FXS) is an inheritable neuropsychological disease caused by silence of the fmr1 gene and the deficiency of Fragile X mental retardation protein (FMRP). Patients present neuronal alterations that lead to severe intellectual disability and altered sleep rhythms. However, the neural circuit mechanisms underlying FXS remain unclear. Previous studies have suggested that metabolic glutamate and gamma-aminobutyric acid (GABA) receptors/circuits are two counter-balanced factors involved in FXS pathophysiology. More and more studies demonstrated that attenuated GABAergic circuits in the absence of FMRP are critical for abnormal progression of FXS. Here, we reviewed the changes of GABA neural circuits that were attributed to intellectual-deficient FXS, from several aspects including deregulated GABA metabolism, decreased expressions of GABA receptor subunits, and impaired GABAergic neural circuits. Furthermore, the activities of GABA neural circuits are modulated by circadian rhythm of FMRP metabolism and reviewed the abnormal condition of FXS mice or patients.

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.

Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment.

In vivo toxicity assessment of aflatoxin B1-contaminated corn after ozone degradation.

Corn is an important food and feedstuff in China and worldwide. The problems caused by aflatoxin B1-contaminated corn (ACC) are of great concern. Our previous studies have demonstrated that ozone can effectively degrade AFB1 in corn, prompting us to investigate the in vivo toxicity of treated ACC. In this study, 35 Kunming mice were used to assess the in vivo toxicity of ozone treated ACC. Results indicated that compared to mice fed with basal feedstuff (provided by the Shanghai SLAC Laboratory), those fed with ACC have significantly decreased mean weight as well as total protein (TP), albumin (ALB), and globulin (GLB) contents (p < 0.05). On the other hand, the liver and kidney/body weight ratio as well as the serum alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels significantly increased (p < 0.05). Obvious histopathological changes were found in the liver and kidney. When mice were fed with the ozone-treated ACC, no significant differences were observed in the mean weight, the liver and kidney/body weight ratio and in the major serum indexes ALT, TP, ALB, and GLB (p > 0.05). However, AST and ALP significantly increased (p < 0.05), and slight histopathological changes were found in liver tissues. This study indicated that ACC may lead to significant changes in various physiological characteristics and biochemical indexes in liver and kidney tissues, but ozone treatment of ACC could significantly reduce these changes.