The phosphodiesterase DibA interacts with the c-di-GMP receptor LapD and specifically regulates biofilm in Pseudomonas putida.

The ubiquitous bacterial second messenger c-di-GMP is synthesized by diguanylate cyclase and degraded by c-di-GMP-specific phosphodiesterase. The genome of Pseudomonas putida contains dozens of genes encoding diguanylate cyclase/phosphodiesterase, but the phenotypical-genotypical correlation and functional mechanism of these genes are largely unknown. Herein, we characterize the function and mechanism of a P. putida phosphodiesterase named DibA. DibA consists of a PAS domain, a GGDEF domain, and an EAL domain. The EAL domain is active and confers DibA phosphodiesterase activity. The GGDEF domain is inactive, but it promotes the phosphodiesterase activity of the EAL domain via binding GTP. Regarding phenotypic regulation, DibA modulates the cell surface adhesin LapA level in a c-di-GMP receptor LapD-dependent manner, thereby inhibiting biofilm formation. Moreover, DibA interacts and colocalizes with LapD in the cell membrane, and the interaction between DibA and LapD promotes the PDE activity of DibA. Besides, except for interacting with DibA and LapD itself, LapD is found to interact with 11 different potential diguanylate cyclases/phosphodiesterases in P. putida, including the conserved phosphodiesterase BifA. Overall, our findings demonstrate the functional mechanism by which DibA regulates biofilm formation and expand the understanding of the LapD-mediated c-di-GMP signaling network in P. putida.

Epithelial TIPE1 Protein Guards against Colitis by Inhibiting TNF-α-Mediated Inflammation.

Intestinal epithelial cells (IECs) at the internal/external interface orchestrate the mucosal immune response, and IEC dysfunction has been linked to multiple inflammatory diseases, including inflammatory bowel disease. In this study, we found that a member of the TNF-α-induced protein 8 (TNFAIP8 or TIPE) family called TIPE1 is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. TIPE1-deficient mice, or chimeric mice that were deficient in TIPE1 in their nonhematopoietic cells, were more sensitive to dextran sulfate sodium-induced experimental colitis; however, TIPE1 deficiency had no impact on the development of inflammation-associated and sporadic colorectal cancers. Mechanistically, TIPE1 prevented experimental colitis through modulation of TNF-α-dependent inflammatory response in IECs. Importantly, genetic deletion of both TIPE1 and its related protein TNFAIP8 in mice led to the development of spontaneous chronic colitis, indicating that both of these two TIPE family members play crucial roles in maintaining intestinal homeostasis. Collectively, our findings highlight an important mechanism by which TIPE family proteins maintain intestinal homeostasis and prevent inflammatory disorders in the gut.

Aberrant splicing of CaV1.2 calcium channel induced by decreased Rbfox1 enhances arterial constriction during diabetic hyperglycemia.

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague-Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current-voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.

Dysregulated Rbfox2 produces aberrant splicing of CaV1.2 calcium channel in diabetes-induced cardiac hypertrophy.

BACKGROUND: L-type Ca2+ channel CaV1.2 is essential for cardiomyocyte excitation, contraction and gene transcription in the heart, and abnormal functions of cardiac CaV1.2 channels are presented in diabetic cardiomyopathy. However, the underlying mechanisms are largely unclear. The functions of CaV1.2 channels are subtly modulated by splicing factor-mediated alternative splicing (AS), but whether and how CaV1.2 channels are alternatively spliced in diabetic heart remains unknown. METHODS: Diabetic rat models were established by using high-fat diet in combination with low dose streptozotocin. Cardiac function and morphology were assessed by echocardiography and HE staining, respectively. Isolated neonatal rat ventricular myocytes (NRVMs) were used as a cell-based model. Cardiac CaV1.2 channel functions were measured by whole-cell patch clamp, and intracellular Ca2+ concentration was monitored by using Fluo-4 AM. RESULTS: We find that diabetic rats develop diastolic dysfunction and cardiac hypertrophy accompanied by an increased CaV1.2 channel with alternative exon 9* (CaV1.2E9*), but unchanged that with alternative exon 8/8a or exon 33. The splicing factor Rbfox2 expression is also increased in diabetic heart, presumably because of dominate-negative (DN) isoform. Unexpectedly, high glucose cannot induce the aberrant expressions of CaV1.2 exon 9* and Rbfox2. But glycated serum (GS), the mimic of advanced glycation end-products (AGEs), upregulates CaV1.2E9* channels proportion and downregulates Rbfox2 expression in NRVMs. By whole-cell patch clamp, we find GS application hyperpolarizes the current-voltage curve and window currents of cardiac CaV1.2 channels. Moreover, GS treatment raises K+-triggered intracellular Ca2+ concentration ([Ca2+]i), enlarges cell surface area of NRVMs and induces hypertrophic genes transcription. Consistently, siRNA-mediated knockdown of Rbfox2 in NRVMs upregulates CaV1.2E9* channel, shifts CaV1.2 window currents to hyperpolarization, increases [Ca2+]i and induces cardiomyocyte hypertrophy. CONCLUSIONS: AGEs, not glucose, dysregulates Rbfox2 which thereby increases CaV1.2E9* channels and hyperpolarizes channel window currents. These make the channels open at greater negative potentials and lead to increased [Ca2+]i in cardiomyocytes, and finally induce cardiomyocyte hypertrophy in diabetes. Our work elucidates the underlying mechanisms for CaV1.2 channel regulation in diabetic heart, and targeting Rbfox2 to reset the aberrantly spliced CaV1.2 channel might be a promising therapeutic approach in diabetes-induced cardiac hypertrophy.

Wsp system oppositely modulates antibacterial activity and biofilm formation via FleQ-FleN complex in Pseudomonas putida.

Type VI secretion systems (T6SS) are specific antibacterial weapons employed by diverse bacteria to protect themselves from competitors. Pseudomonas putida KT2440 possesses a functional T6SS (K1-T6SS) and exhibits antibacterial activity towards a broad range of bacteria. Here we found that the Wsp signal transduction system regulated K1-T6SS expression via synthesizing the second messenger cyclic di-GMP (c-di-GMP), thus mediating antibacterial activity in P. putida. High-level c-di-GMP produced by Wsp system repressed the transcription of K1-T6SS genes in structural operon and vgrG1 operon. Transcriptional regulator FleQ and ATPase FleN functioned as repressors in the Wsp system-modulated K1-T6SS transcription. However, FleQ and FleN functioned as activators in biofilm formation, and Wsp system promoted biofilm formation largely in a FleQ/FleN-dependent manner. Furthermore, FleQ-FleN complex bound directly to the promoter of K1-T6SS structural operon in vitro, and c-di-GMP promoted the binding. Besides, P. putida biofilm cells showed higher c-di-GMP levels and lower antibacterial activity than planktonic cells. Overall, our findings reveal a mechanism by which Wsp system oppositely modulates antibacterial activity and biofilm formation via FleQ-FleN, and demonstrate the relationship between plankton/biofilm lifestyles and antibacterial activity in P. putida.

Diminished Rbfox1 increases vascular constriction by dynamically regulating alternative splicing of CaV1.2 calcium channel in hypertension.

Calcium influx from depolarized CaV1.2 calcium channels triggers the contraction of vascular smooth muscle cells (VSMCs), which is important for maintaining vascular myogenic tone and blood pressure. The function of CaV1.2 channel can be subtly modulated by alternative splicing (AS), and its aberrant splicing involves in the pathogenesis of multiple cardiovascular diseases. The RNA-binding protein Rbfox1 is reported to regulate the AS events of CaV1.2 channel in the neuronal development, but its potential roles in vascular CaV1.2 channels and vasoconstriction remain undefined. Here, we detect Rbfox1 is expressed in rat vascular smooth muscles. Moreover, the protein level of Rbfox1 is dramatically decreased in the hypertensive small arteries from spontaneously hypertensive rats in comparison with normotensive ones from Wistar-Kyoto rats. In VSMCs, Rbfox1 could dynamically regulate the AS of CaV1.2 exons 9* and 33. By whole-cell patch clamp, we identify knockdown of Rbfox1 induces the hyperpolarization of CaV1.2 current-voltage relationship curve in VSMCs. Furthermore, siRNA-mediated knockdown of Rbfox1 increases the K+-induced constriction of rat mesenteric arteries. In summary, our results indicate Rbfox1 modulates vascular constriction by dynamically regulating CaV1.2 alternative exons 9* and 33. Therefore, our work elucidates the underlying mechanisms for CaV1.2 channels regulation and provides a potential therapeutic target for hypertension.

Layer-Tunable Nonlinear Optical Characteristics and Photocarrier Dynamics of 2D PdSe2 in Broadband Spectra.

Layered 2D transition metal dichalcogenides (TMDCs) exhibited fascinating nonlinear optical (NLO) properties for constructing varied promising optoelectronics. However, exploring the desired 2D materials with both superior nonlinear absorption and ultrafast response in broadband spectra remain the key challenges to harvest their greatest potential. Here, based on synthesizing 2D PdSe2 films with the controlled layer number, the authors systematically demonstrated the broadband giant NLO performance and ultrafast excited carrier dynamics of this emerging material under femtosecond visible-to-near-infrared laser-pulse excitation (400-1550 nm). Layer-dependent and wavelength-dependent evolution of optical bandgap, nonlinear absorption, and photocarrier dynamics in the obtained 2D PdSe2 are clearly revealed. Specially, the transition from semiconducting to semimetallic PdSe2 induced dramatic changes of their interband absorption-relaxation process. This work makes 2D PdSe2 more competitive for future ultrafast photonics and also opens up a new avenue for the optical performance optimization of various 2D materials by rational design of these materials.

Aberrant Exon 8/8a Splicing by Downregulated PTBP (Polypyrimidine Tract-Binding Protein) 1 Increases CaV1.2 Dihydropyridine Resistance to Attenuate Vasodilation.

OBJECTIVE: Calcium channel blockers, such as dihydropyridines, are commonly used to inhibit enhanced activity of vascular CaV1.2 channels in hypertension. However, patients who are insensitive to such treatments develop calcium channel blocker-resistant hypertension. The function of CaV1.2 channel is diversified by alternative splicing, and the splicing factor PTBP (polypyrimidine tract-binding protein) 1 influences the utilization of mutually exclusive exon 8/8a of the CaV1.2 channel during neuronal development. Nevertheless, whether and how PTBP1 makes a role in the calcium channel blocker sensitivity of vascular CaV1.2 channels, and calcium channel blocker-induced vasodilation remains unknown. Approach and Results: We detected high expression of PTBP1 and, inversely, low expression of exon 8a in CaV1.2 channels (CaV1.2E8a) in rat arteries. In contrast, the opposite expression patterns were observed in brain and heart tissues. In comparison to normotensive rats, the expressions of PTBP1 and CaV1.2E8a channels were dysregulated in mesenteric arteries of hypertensive rats. Notably, PTBP1 expression was significantly downregulated, and CaV1.2E8a channels were aberrantly increased in dihydropyridine-resistant arteries compared with dihydropyridine-sensitive arteries of rats and human. In rat vascular smooth muscle cells, PTBP1 knockdown resulted in shifting of CaV1.2 exon 8 to 8a. Using patch-clamp recordings, we demonstrated a concomitant reduction of sensitivity of CaV1.2 channels to nifedipine, due to the higher expression of CaV1.2E8a isoform. In vascular myography experiments, small interfering RNA-mediated knockdown of PTBP1 attenuated nifedipine-induced vasodilation of rat mesenteric arteries. CONCLUSIONS: PTBP1 finely modulates the sensitivities of CaV1.2 channels to dihydropyridine by shifting the utilization of exon 8/8a and resulting in changes of responses in dihydropyridine-induced vasodilation.

Preparation of Nano-TiO2 by a Surfactant-Free Microemulsion-Hydrothermal Method and Its Photocatalytic Activity.

The TiO2 nanoparticles with high photocatalytic activity were prepared by the surfactant-free microemulsion (SFME)-hydrothermal method at lower temperatures using oil-in-water SFME systems as templates. The phase diagram of the SFME ethyl acetate (EA)/propan-2-ol/water was determined by electrical conductivity and UV-visible spectroscopy. The synthesized TiO2 nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, and N2 adsorption-desorption techniques. They were all assigned to the anatase phase and showed type IV adsorption-desorption isotherms with type H2 hysteresis loops. As the EA content (fO) of the SFME decreases, the Brunauer-Emmett-Teller (BET) specific surface area (SBET) of the TiO2 nanoparticles increases. This results in an increase in the photocatalytic activity of the TiO2 nanoparticles. With an increase in temperature, the photocatalytic activity of the TiO2 nanoparticles increases significantly, whereas the SBET values decrease and the crystal size increases. Under the same conditions, the degradation rate of the TiO2 prepared at 190 °C reaches 97%, which is significantly higher than that of Degussa P-25 (66%). This may be due to the use of the SFME system to synthesize the TiO2 nanoparticles, which avoids the blocking effects of surfactant molecules on the active sites of the nanoparticles.

A Multifunctional Imidazolium-Based Silicone Material with Conductivity, Self-Healing, Fluorescence, and Stretching Sensitivity.

Wearable devices have gained substantial interest for a wide range of applications, including biomonitoring and entertainment. They are basically composed of sensors and substrate materials. Recently, silicone materials have been extensively used in wearable devices because of their unique properties. Silicone materials, which possess remarkable insulation, predominantly serve as a substrate instead of a signaling material due to the indispensable electrical conductivity in wearable devices. Herein, a novel kind of silicone material, with both good conductivity and excellent self-healing efficiency, is designed by introducing imidazolium into the silicone polymer in one step. The free ions afford an ionic conductivity as high as 2.79 × 10-4 S m-1 , representing a significant improvement over traditional silicone materials. Because of the good conductivity, the silicone material is sensitive to stretching and can be applied as a flexible sensor. On the other hand, the material exhibits a high healing efficiency, reaching 89% in 6 h, due to the dynamic supramolecular interaction of the ion crosslink sites at the crack surface. Furthermore, the silicone material emits a yellow-green fluorescence under UV light.

Screening the Marker Components in Psoralea corylifolia L. with the Aids of Spectrum-Effect Relationship and Component Knock-Out by UPLC-MS².

Psoralea corylifolia L., (P. corylifolia), which is used for treating vitiligo in clinic, shows inhibitory and activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to determine the active ingredients in the ethenal extracts of P. corylifolia on tyrosinase activity. The spectrum-effect relationship and knock-out method were established to predict the active compounds. Their structures were then identified with the high resolution mass spectra. A high performance liquid chromatography method was established to obtain the specific chromatograms. Tyrosinase activity in vitro was assayed by the method of oxidation rate of levodopa. Partial least squares method was used to test the spectrum-effect relationships. Chromatographic peaks P2, P4, P9, P10, P11, P13, P21, P26, P28, and P30 were positively related to the activating effects on tyrosinase activity in PE, whereas chromatographic peaks P1, P3, P6, P14, P16, P19, P22, and P29 were negatively related to the activating effects on tyrosinase in the P. corylifolia (PEs). When the sample concentration was 0.5 g·mL-1, equal to the amount of raw medicinal herbs, the target components were daidzein (P2), psoralen (P5), neobavaisoflavone (P13), and psoralidin (P20), which were consistent with the results of spectrum-effect relationships.

LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats.

Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3ß. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases. AIMS: This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats. METHODS: Livers from type 2 diabetic rats and hepatocytes cultured in high glucose and high fatty acid media were studied. The changes in expression of AKT, GK and GSK 3ß were detected by western blotting or RT-PCR. The application of bioinformatics technology (CatRAPID) was used to identify the targets of NONRATT021972 RNA. RESULTS: We found that lncRNA NONRATT021972 levels in the liver were increased in type 2 diabetic rats, and the increase was associated with an increase in the blood glucose levels. The NONRATT021972 siRNA enhanced phospho-AKT (p-AKT) levels, GK expression and hepatic glycogen synthesis. This siRNA also reduced phospho-glycogen synthase kinase-3ß (p-GSK-3ß) levels and hyperglycemia in T2DM rats, as well as in hepatocytes cultured in high glucose media with fatty acids. CatRAPID predicted that there was the interaction between NONRATT021972 and p-AKT. CONCLUSIONS: LncRNA NONRATT021972 siRNA may have beneficial effects on T2DM.

Temperature-Sensitive Artificial Channels through Pillar[5]arene-based Host-Guest Interactions.

In living systems, temperature-sensitive ion channels play a vital role in numerous cellular processes and can be controlled by biological ion channels in response to specific temperature stimuli. Facile pillar[5]arene-based host-guest interactions are introduced into a nanochannel pattern for constructing a temperature-sensitive artificial channel. Ion transport was switched from cations to anions by controlling the extent of the host bound to the guest with temperature stimuli. This efect is mainly due to the changing of the inner surface charge and wettability of the nanochannel during the process. This study paves a new way for better understanding the mechanism of temperature-sensitive properties and shows great promise for biomedical research.

Zn(2+) and EDTA Cooperative Switchable Nanofluidic Diode Based on Asymmetric Modification of Single Nanochannel.

Design and fabrication of smart switchable nanofluidic diodes remains a challenge in the life and materials sciences. Here, we present the first example of a novel Zn(2+)/EDTA switchable nanofluidic diode system based on the control of one-side of the modified hourglass-shaped nanochannel with salicylaldehyde Schiff base (SASB). The nanofluidic diode can be turned on in the response of Zn(2+) and turned off in response to EDTA solution with good reversibility and recyclability.

P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor.

Activation of P2X7 receptors decreases the proliferation of murine luteal cells.

Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38-mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.

Effects of intermedin on dorsal root ganglia in the transmission of neuropathic pain in chronic constriction injury rats.

Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. The P2X3 receptor plays a crucial role in facilitating pain transmission. Intermedin (IMD), which is also known as adrenomedullin 2 (AMD2) is a newly discovered hormone that is a member of the calcitonin/calcitonin gene-related peptide family. The present research investigates the effects of IMD on pain transmission in neuropathic pain states as mediated by P2X3 receptors in dorsal root ganglia (DRG). Chronic constriction injury (CCI) rats were used as the neuropathic pain model. Adult male Sprague-Dawley rats were randomly assigned to five groups as follows: blank control group (Control), sham operation group (Sham), CCI rats treated with saline group (CCI+NS), CCI rats treated with IMD1-53 group (CCI+IMD1-53 ), and CCI rats treated with IMD inhibitor IMD14-47 group (CCI+IMD14-47 ). The mechanical withdrawal threshold (MWT) was tested by the von Frey method, and the thermal withdrawal latency (TWL) was tested via automatic thermal stimulus instruments. Changes in the expression of P2X3 receptors and IMD in CCI rat L4/L5 DRG were detected using immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting. After treatment with intrathecal injection (i.t.), mechanical and thermal hyperalgesia in the CCI+IMD1-53 group was maintained, but MWT and TWL in the CCI+IMD14-47 groups increased. The expression levels of P2X3 receptors and IMD in L4/L5 DRG in the CCI+NS and CCI+IMD1-53 groups were significantly increased compared with those in the Control group or the Sham group. After application of IMD14-47 in CCI rats, there was a decrease in the expression levels of P2X3 receptors and IMD in L4/L5 DRG. The phosphorylation of p38 and ERK1/2 in L4/L5 DRG in the CCI+NS group and the CCI+IMD1-53 group was stronger than that in the Control group or the Sham group; however, the phosphorylation of p38 and ERK1/2 in the CCI+IMD14-47 group was much lower than that in the CCI+NS group or the CCI+IMD1-53 group. Our findings indicate that IMD might increase the sensitization effects of IMD on P2X3 receptors to alleviate chronic neuropathic pain injury. The IMD agonist IMD1-53 might enhance nociceptive responses mediated by P2X3 receptors in neuropathic pain, and the IMD inhibitor IMD14-47 could inhibit the sensitization of the P2X3 receptor in chronic neuropathic pain injury.

Design and fabrication of a biomimetic nanochannel for highly sensitive arginine response in serum samples.

Inspired from their biological counterparts, chemical modification of the interior surface of nanochannels with functional molecules may provide a highly efficient means to control ionic or molecular transport through nanochannels. Herein, we have designed and prepared a aldehyde calix[4]arene (C4AH), which was attached to the interior surface of a single nanochannel by using a click reaction, and that showed a high response for arginine (Arg). Furthermore, the nanofluidic sensing system has been challenged with complex matrices containing a high concentration of interfering sequences and serum. Based on this finding, we believe that the artificial nanochannel can be used for practical Arg-sensing devices, and be applied in a biological environment.

RADseq-based population genomic analysis and environmental adaptation of rare and endangered recretohalophyte Reaumuria trigyna.

Genetic diversity reflects the survival potential, history, and population dynamics of an organism. It underlies the adaptive potential of populations and their response to environmental change. Reaumuria trigyna is an endemic species in the Eastern Alxa and West Ordos desert regions in China. The species has been considered a good candidate to explore the unique survival strategies of plants that inhabit this area. In this study, we performed population genomic analyses based on restriction-site associated DNA sequencing to understand the genetic diversity, population genetic structure, and differentiation of the species. Analyses of 92,719 high-quality single-nucleotide polymorphisms (SNPs) indicated that overall genetic diversity of R. trigyna was low (HO = 0.249 and HE = 0.208). No significant genetic differentiation was observed among the investigated populations. However, a subtle population genetic structure was detected. We suggest that this might be explained by adaptive diversification reinforced by the geographical isolation of populations. Overall, 3513 outlier SNPs were located in 243 gene-coding sequences in the R. trigyna transcriptome. Potential sites under diversifying selection occurred in genes (e.g., AP2/EREBP, E3 ubiquitin-protein ligase, FLS, and 4CL) related to phytohormone regulation and synthesis of secondary metabolites which have roles in adaptation of species. Our genetic analyses provide scientific criteria for evaluating the evolutionary capacity of R. trigyna and the discovery of unique adaptions. Our findings extend knowledge of refugia, environmental adaption, and evolution of germplasm resources that survive in the Ordos area.

Reducing greenhouse gas intensity using a mixture of controlled-release urea and common urea combining suitable maize varieties in a summer maize system.

The one-time application of common urea blended with controlled-release urea (CRU) is considered effective for improving nitrogen use efficiency and grain yield and reducing the greenhouse gas emissions of summer maize in intensive agricultural systems. However, the trade-off between the economic and environmental performances of different blended fertilizer treatments for different maize varieties remains unclear. Therefore, a consecutive two-year field experiment was conducted in the North China Plain to study the effects of different ratios of CRU and common urea on the yield, nitrous oxide (N2O) emissions, yield-scaled total N2O emissions, greenhouse gas intensity (GHGI), and net ecosystem economic benefit (NEEB) in 2021 and 2022. Four N fertilizer treatments with equal rate at 180 kg N ha-1 were applied as N180U (all Urea), N180C1(1/3CRU), N180C2(2/3CRU), and N180C (all CRU), and two maize varieties (JNK728-yellow ripe variety and ZD958-green ripe variety) were used. The N180C1 and N180C2 treatments produced the highest grain yield in varieties JNK728 and ZD958 (9.4-11.5 t ha-1 and 9.0-11.0 t ha-1), respectively. Compared to the N180U treatment (conventional method), the N180C1 treatment reduced the GHGI (24.8 %-25.9 %) and increased the NEEB (33.1 %-33.4 %) in the JNK728 variety, whereas the N180C2 treatment reduced the GHGI (16.9 %-28.8 %) and increased the NEEB (27.2 %-48.1 %) in the ZD958 variety. The study concludes that a one-time application of blended nitrogen fertilizer in suitable varieties can minimize the GHGI and maximize the NEEB, which is an effective strategy for balancing yield and nitrogen efficiency in the summer maize system in the North China Plain.