Genome-wide identification and expression characterization of the GH3 gene family of tea plant (Camellia sinensis).

To comprehensively understand the characteristics of the GH3 gene family in tea plants (Camellia sinensis), we identified 17 CsGH3 genes and analyzed their physicochemical properties, phylogenetic relationships, gene structures, promoters, and expression patterns in different tissues. The study showed that the 17 CsGH3 genes are distributed on 9 chromosomes, and based on evolutionary analysis, the CsGH3 members were divided into three subgroups. Gene duplication analysis revealed that segmental duplications have a significant impact on the amplification of CsGH3 genes. In addition, we identified and classified cis-elements in the CsGH3 gene promoters and detected elements related to plant hormone responses and non-biotic stress responses. Through expression pattern analysis, we observed tissue-specific expression of CsGH3.3 and CsGH3.10 in flower buds and roots. Moreover, based on predictive analysis of upstream regulatory transcription factors of CsGH3, we identified the potential transcriptional regulatory role of gibberellin response factor CsDELLA in CsGH3.14 and CsGH3.15. In this study, we found that CsGH3 genes are involved in a wide range of activities, such as growth and development, stress response, and transcription. This is the first report on CsGH3 genes and their potential roles in tea plants. In conclusion, these results provide a theoretical basis for elucidating the role of GH3 genes in the development of perennial woody plants and offer new insights into the synergistic effects of multiple hormones on plant growth and development in tea plants.

Advances in contezolid: novel oxazolidinone antibacterial in Gram-positive treatment.

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.

Inhibitory Activity Against Rhizoctonia Solani and Chemical Composition of Extract from Moutan Cortex.

Rice sheath blight (RSB), caused by Rhizoctonia solani, is a significant disease of rice. The negative effects of chemical fungicides have created an urgent need for low-toxicity botanical fungicides. Our previous research revealed that the ethanol crude extract of Moutan Cortex (MC) exhibited superior antifungal activity against R. solani at 1000 µg/mL, resulting in a 100 % inhibition rate. The antifungal properties were mainly found in the petroleum ether extract. However, the active ingredients of the extract are still unclear. In this study, gas chromatography-mass spectrometry (GC-MS) was utilised for the analysis of its chemical components. The mycelium growth rate method was utilized to detect the antifungal activity. The findings indicated that paeonol constituted the primary active component, with a content of more than 96 %. Meanwhile, paeonol was the most significant antifungal active ingredient, the antifungal activity of paeonol (EC50=44.83 µg/mL) was much higher than that of ß-sitosterol and ethyl propionate against R. solani. Observation under an optical microscope revealed that paeonol resulted in abnormal mycelial morphology. This study provided theoretical support for identifying monomer antifungal compounds and developing biological fungicides for R. solani.

Progress on genomics and locus of important agronomic traits in Chenopodium quinoa.

Quinoa (Chenopodium quinoa, Willd.) as a new health food in the 20th century, its comprehensive nutritional composition, stress resistance and other characteristics have been paid much of attention, and enjoys the reputation of "nutritional gold", "vegetarian king" and "food in the future" in the world. In recent years, with the rapid development of genomics and high-throughput sequencing technology, the high-quality whole genome sequence of quinoa has been completed, and the omics analysis and functional research of a series of key genes have been gradually carried out. In this review, we summarize the research progress in quinoa genomics, gene family analysis of important transcription factors, genetic map construction, QTL mapping of important traits, and genes for important agronomic and yield traits. Moreover, according to the current status of quinoa breeding, this paper also put forward five key problems in quinoa breeding, and pointed out four important directions of genetic improvement and breeding of quinoa in the future, so as to provide reference for the realization of directional genetic improvement of quinoa in the future.

Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes to drug-induced diarrhea.

Diarrhea is one of the most common adverse side effects observed in ∼7% of individuals consuming Food and Drug Administration (FDA)-approved drugs. The mechanism of how these drugs alter fluid secretion in the gut and induce diarrhea is not clearly understood. Several drugs are either substrates or inhibitors of multidrug resistance protein 4 (MRP4), such as the anti-colon cancer drug irinotecan and an anti-retroviral used to treat HIV infection, 3'-azido-3'-deoxythymidine (AZT). These drugs activate cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluid secretion by inhibiting MRP4-mediated cAMP efflux. Binding of drugs to MRP4 augments the formation of MRP4-CFTR-containing macromolecular complexes that is mediated via scaffolding protein PDZK1. Importantly, HIV patients on AZT treatment demonstrate augmented MRP4-CFTR complex formation in the colon, which defines a novel paradigm of drug-induced diarrhea.

Altered cGMP dynamics at the plasma membrane contribute to diarrhea in ulcerative colitis.

Ulcerative colitis (UC) belongs to inflammatory bowel disorders, a group of gastrointestinal disorders that can produce serious recurring diarrhea in affected patients. The mechanism for UC- and inflammatory bowel disorder-associated diarrhea is not well understood. The cystic fibrosis transmembrane-conductance regulator (CFTR) chloride channel plays an important role in fluid and water transport across the intestinal mucosa. CFTR channel function is regulated in a compartmentalized manner through the formation of CFTR-containing macromolecular complexes at the plasma membrane. In this study, we demonstrate the involvement of a novel macromolecular signaling pathway that causes diarrhea in UC. We found that a nitric oxide-producing enzyme, inducible nitric oxide synthase (iNOS), is overexpressed under the plasma membrane and generates compartmentalized cGMP in gut epithelia in UC. The scaffolding protein Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) bridges iNOS with CFTR, forming CFTR-NHERF2-iNOS macromolecular complexes that potentiate CFTR channel function via the nitric oxide-cGMP pathway under inflammatory conditions both in vitro and in vivo. Potential disruption of these complexes in Nherf2(-/-) mice may render them more resistant to CFTR-mediated secretory diarrhea than Nherf2(+/+) mice in murine colitis models. Our study provides insight into the mechanism of pathophysiologic occurrence of diarrhea in UC and suggests that targeting CFTR and CFTR-containing macromolecular complexes will ameliorate diarrheal symptoms and improve conditions associated with inflammatory bowel disorders.

Asymmetrical macromolecular complex formation of lysophosphatidic acid receptor 2 (LPA2) mediates gradient sensing in fibroblasts.

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca(2+) puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca(2+) puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts.

Stabilizing rescued surface-localized δf508 CFTR by potentiation of its interaction with Na(+)/H(+) exchanger regulatory factor 1.

Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in CFTR, a plasma-membrane-localized anion channel. The most common mutation in CFTR, deletion of phenylalanine at residue 508 (ΔF508), causes misfolding of CFTR resulting in little or no protein at the plasma membrane. The CFTR corrector VX-809 shows promise for treating CF patients homozygous for ΔF508. Here, we demonstrate the significance of protein-protein interactions in enhancing the stability of the ΔF508 CFTR mutant channel protein at the plasma membrane. We determined that VX-809 prolongs the stability of ΔF508 CFTR at the plasma membrane. Using competition-based assays, we demonstrated that ΔF508 CFTR interacts poorly with Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) compared to wild-type CFTR, and VX-809 significantly increased this binding affinity. We conclude that stabilized CFTR-NHERF1 interaction is a determinant of the functional efficiency of rescued ΔF508 CFTR. Our results demonstrate the importance of macromolecular-complex formation in stabilizing rescued mutant CFTR at the plasma membrane and suggest this to be foundational for the development of a new generation of effective CFTR-corrector-based therapeutics.

MAST205 competes with cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand for binding to CFTR to regulate CFTR-mediated fluid transport.

The PDZ (postsynaptic density-95/discs large/zona occludens-1) domain-based interactions play important roles in regulating the expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR). Several PDZ domain-containing proteins (PDZ proteins for short) have been identified as directly or indirectly interacting with the C terminus of CFTR. To better understand the regulation of CFTR processing, we conducted a genetic screen and identified MAST205 (a microtubule-associated serine/threonine kinase with a molecular mass of 205 kDa) as a new CFTR regulator. We found that overexpression of MAST205 increased the expression of CFTR and augmented CFTR-mediated fluid transport in a dose-dependent manner. Conversely, knockdown of MAST205 inhibited CFTR function. The PDZ motif of CFTR is required for the regulatory role of MAST205 in CFTR expression and function. We further demonstrated that MAST205 and the CFTR-associated ligand competed for binding to CFTR, which facilitated the processing of CFTR and consequently up-regulated the expression and function of CFTR at the plasma membrane. More importantly, we found that MAST205 could facilitate the processing of F508del-CFTR mutant and augment its quantity and channel function at the plasma membrane. Taken together, our data suggest that MAST205 plays an important role in regulating CFTR expression and function. Our findings have important clinical implications for treating CFTR-associated diseases such as cystic fibrosis and secretory diarrheas.

Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides.

It has long been known that cyclic nucleotides and cyclic nucleotide-dependent signaling molecules control cell migration. However, the concept that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules that regulates cell migration, is new and revolutionary. In this study, we used multidrug resistance protein 4 (MRP4)-expressing cell lines and MRP4 knock-out mice as model systems and wound healing assays as the experimental system to explore this unique and emerging concept. MRP4, a member of a large family of ATP binding cassette transporter proteins, localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a role in the regulation of intracellular cyclic nucleotide levels. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) isolated from Mrp4(-/-) mice have higher intracellular cyclic nucleotide levels and migrate faster compared with MEFs from Mrp4(+/+) mice. Using FRET-based cAMP and cGMP sensors, we show that inhibition of MRP4 with MK571 increases both cAMP and cGMP levels, which results in increased migration. In contrast to these moderate increases in cAMP and cGMP levels seen in the absence of MRP4, a robust increase in cAMP levels was observed following treatment with forskolin and isobutylmethylxanthine, which decreases fibroblast migration. In response to externally added cell-permeant cyclic nucleotides (cpt-cAMP and cpt-cGMP), MEF migration appears to be biphasic. Altogether, our studies provide the first experimental evidence supporting the novel concept that balance between cyclic nucleotides is critical for cell migration.

Correction: Li et al. Optimizing Soil Health and Sorghum Productivity through Crop Rotation with Quinoa. Life 2024, 14, 745.

The author Wenbin Bai has been changed to the second corresponding author [...].

Optimizing Soil Health and Sorghum Productivity through Crop Rotation with Quinoa.

Crop rotation has been considered a potential solution to mitigate the negative effects of the continuous cropping of sorghum, including soil quality issues, inadequate plant development, and diminished yield and quality. A two-year field experiment was conducted to compare the effects of sorghum-sorghum continuous cropping and quinoa-sorghum rotation on soil properties and sorghum yield. The treatments were arranged in a randomized complete block design with three replicates. Sorghum seeds (Jinza 22) and quinoa seeds ('Jiaqi 1' variety) were used. Soil samples were collected before and during the experiment for the analysis of physicochemical properties. The yield traits of sorghum were measured at maturity. The results showed that soil nutrients and organic matter were higher in the top 0-20 cm soil depth compared to 20-40 cm depth, with significant differences observed between cropping systems. Sorghum-quinoa cropping increased soil total N and organic matter, particularly at the jointing and maturity stages of sorghum. However, the available phosphorus was higher under continuous cropping at all growth stages. Crop rotation significantly improved sorghum yield traits, including spike fresh weight, spike dry weight, grain weight per spike, and grain yield per hectare. A correlation analysis revealed positive relationships between soil total N, organic matter, and sorghum yield. Overall, sorghum-quinoa rotation demonstrated potential for improving soil fertility and enhancing crop productivity compared to continuous cropping, although further studies are needed to explore the long-term effects and optimize management practices.

Effects of Nitrogen Accumulation, Transportation, and Grain Nutritional Quality and Advances in Fungal Endophyte Research in Quinoa (Chenopodium quinoa Willd.) Plants.

This study aims to understand the influence of nitrogen accumulation, fungal endophyte, yield, nitrogen use efficiency, and grain nutritional quality parameters on the yield of quinoa in some areas of China. The endophytic microbial community in plants plays a crucial role in plant growth, development, and health, especially in quinoa plants under different nitrogen fertilizer levels. The results from the present study indicated that appropriate nitrogen application significantly enhanced the nitrogen accumulation and yield of quinoa grains during maturity, increasing by 34.54-42.18% and 14.59-30.71%, respectively. Concurrently, protein content, amylose, total starch, ash, and fat content also increased, with respective growth rates of 1.15-18.18%, 30.74-42.53%, 6.40-12.40%, 1.94-21.94%, and 5.32-22.22%. Our constructed interaction network of bacterial and fungal communities revealed that bacteria outnumbered fungi significantly, and most of them exhibited synergistic interactions. The moderate increase in N150 was beneficial for increasing quinoa yield, achieving nitrogen use efficiency (NUE) of over 20%. The N210 was increased, and both the yield and NUE significantly decreased. This study provides novel insights into the impact of nitrogen fertilizer on quinoa growth and microbial communities, which are crucial for achieving agricultural sustainable development.

Compartmentalization of cyclic nucleotide signaling: a question of when, where, and why?

Preciseness of cellular behavior depends upon how an extracellular cue mobilizes a correct orchestra of cellular messengers and effector proteins spatially and temporally. This concept, termed compartmentalization of cellular signaling, is now known to form the molecular basis of many aspects of cellular behavior in health and disease. The cyclic nucleotides cyclic adenosine monophosphate and cyclic guanosine monophosphate are ubiquitous cellular messengers that can be compartmentalized in three ways: first, by their physical containment; second, by formation of multiple protein signaling complexes; and third, by their selective depletion. Compartmentalized cyclic nucleotide signaling is a very prevalent response among all cell types. In order to understand how it becomes relevant to cellular behavior, it is important to know how it is executed in cells to regulate physiological responses and, also, how its execution or dysregulation can lead to a pathophysiological condition, which forms the scope of the presented review.

Long-Term Nutrient Cycle in Improved Grain Yield of Dryland Winter Wheat (Triticum aestivum L.) under Hydrological Process of Plant Ecosystem Distribution in the Loess Plateau of China.

Precipitation is the major cause of crop yield variation in rainfed agriculture production in the Loess Plateau. As over fertilization is economically and environmentally undesirable, and crop yield and the resulting returns for N input are uncertain when rainfall variability is high, optimizing N management according to precipitation during fallow season is vital for efficient crop water use and high yield in dryland rainfed farming systems. Results show that the nitrogen treatment rate of 180 treatment significantly increased the tiller percentage rate, and the leaf area index at anthesis, the jointing anthesis, anthesis maturity dry matter, and nitrogen accumulation was closely related to yield. N150 treatment compared to N180 treatment significantly increased the percentage of ear-bearing tiller by 7%, dry substance accretion from jointing to anthesis by 9%, and yield by 17% and 15%, respectively. Our study has important implications for the assessment of the effects of fallow precipitation, as well as for the sustainable development of dryland agriculture in the Loess Plateau. Our results indicate that adjusting N fertilizer inputs based on summer rainfall variation could enhance wheat yield in rainfed farming systems.

[Effects of Long-term Tillage on Soil Bacterial Community Structure and Physicochemical Properties of Dryland Wheat Fields in Northern China].

To explore the effects of long-term tillage on bacterial community structure in different soil layers of dryland wheat fields and its relationship with soil physicochemical properties, a long-term field experiment was conducted from 2016 to 2021 in Wenxi Experimental Demonstration Base of Shanxi Agricultural University, Shanxi Province. We studied the effects of no-tillage (NT), subsoiling-tillage (ST), and deep plowing (DP) on soil physicochemical properties; α and ß diversity of the bacterial community; and dominant and different species of phyla and genera in different soil layers. Additionally, PICRUSt2 was used to predict the metabolic function of soil bacterial community. The results revealed that subsoiling-tillage and deep plowing significantly increased the soil water content in the 20-40 cm soil layer and significantly decreased the soil organic carbon content in the 0-20 cm soil layer compared with that under no-tillage for five consecutive years. Compared with that under deep plowing, subsoiling-tillage significantly increased soil water content, soil organic carbon content, dissolved organic carbon content, and dissolved organic nitrogen content in the 0-20 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing increased the α diversity of the soil bacterial community in the 0-40 cm soil layer, and subsoiling-tillage was higher than deep plowing. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundances of Acidobacteria and Nitrospirae in the 0-20 cm soil layer and Acidobacteria, Chloroflexi, Gemmatimonadetes, Rokubacteria, GAL15, and Nitrospirae in the 20-40 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundance of Nitrospira in the 0-20 cm soil layer and Rubrobacter and Streptomyces in the 20-40 cm soil layer. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundance of Acidobacteria and Gemmatimonadetes in the 0-40 cm soil layer. Redundancy analysis demonstrated that the contents of soil organic carbon, dissolved organic carbon, and dissolved organic nitrogen in the 0-20 cm soil layer exerted positive effects on Actinobacteria and Blastococcus, and the soil water content in the 0-40 cm soil layer exerted positive effects on Acidobacteria, Chloroflexi, and Gemmatimonadetes under subsoiling-tillage. The results of PICRUSt2 prediction showed that subsoiling-tillage and deep plowing significantly increased the relative abundance of amino acid metabolism and the metabolism of cofactors and vitamins but decreased the relative abundance of lipid metabolism of bacterial communities in the 20-40 cm soil layer compared with that under no-tillage. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundances of amino acid metabolism in the 0-40 cm soil layer and other amino acid metabolism in the 0-20 cm soil layer. In conclusion, subsoiling-tillage or deep plowing could increase the soil water content, α diversity of the soil bacterial community, and their metabolic capacity in the dryland wheat fields during the summer fallow period. The relative abundance of Acidobacteria and Gemmatimonadetes and the ability of amino acid metabolism of the bacterial community were increased by subsoiling-tillage, and thus the contents of soil dissolved organic carbon and dissolved nitrogen can be increased.

Nitrogen Application Can Optimize Form of Selenium in Soil in Selenium-Rich Areas to Affect Selenium Absorption and Accumulation in Black Wheat.

The composition and form of selenium in the soil have significant effects on the selenium content of crops. In this study, we investigated the selenium absorption pathway in plants by studying the interaction between nitrogen fertilizer and soil selenium. Our results showed that the selenium concentration enrichment factors (CEF) varied within the same region due to nitrogen fertilizer application, where they ranged from 1.33 to 5.02. The soil selenium flow coefficient (mobility factor, MF) increased with higher nitrogen application rates. The sum of the MF values for each soil layer treated with nitrogen application rates of 192 kg hm-2 and 240 kg hm-2 was 0.70, which was 64% higher than that for the control group with no nitrogen application. In the 0-20 cm soil layer, the highest summed water-soluble and exchangeable selenium and relative percentage of total selenium (12.45%) was observed at a nitrogen application rate of 240 kg hm-2. In the 20-40 cm soil layer, the highest relative percentage content of water-soluble and exchangeable selenium and total selenium (12.66%) was observed at a nitrogen application rate of 192 kg hm-2. Experimental treatment of black wheat with various concentrations of sodium selenite showed that selenium treatment at 50 µmol L-1 significantly increased the reduced glutathione (GSH) levels in the leaves and roots of seedlings, where the GSH contents increased by 155.4% in the leaves and by 91.5% in the roots. Further analysis of the soil-black wheat system showed that nitrogen application in selenium-rich areas affected the soil selenium flow coefficient and morphological composition, thereby changing the enrichment coefficient for leaves (0.823), transport capacity from leaves to grains (-0.530), and enrichment coefficient for roots (0.38). These changes ultimately affected the selenium concentration in the grains of black wheat.

A tannic acid-based medical food, Cesinex(®), exhibits broad-spectrum antidiarrheal properties: a mechanistic and clinical study.

BACKGROUND: The purpose of this investigation was to evaluate the efficacy and tolerability of a tannic acid-based medical food, Cesinex(®), in the treatment of diarrhea and to investigate the mechanisms underlying its antidiarrheal effect. METHODS: Cesinex(®) was prescribed to six children and four adults with diarrhea. Patient records were retrospectively reviewed for the primary outcome. Cesinex(®) and its major component, tannic acid, were tested for their effects on cholera toxin-induced intestinal fluid secretion in mice. Polarized human gut epithelial cells (HT29-CL19A cells) were used to investigate the effects of tannic acid on epithelial barrier properties, transepithelial chloride secretion, and cell viability. RESULTS: Successful resolution of diarrheal symptoms was reported in nine of ten patients receiving Cesinex(®). The treatment of HT29-CL19A cells with clinically relevant concentrations of tannic acid (0.01-1 mg/ml) significantly increased transepithelial resistance (TER) and inhibited the cystic fibrosis transmembrane conductance regulator (CFTR)-dependent or the calcium-activated Cl(-) secretion. Tannic acid could also improve the impaired epithelial barrier function induced by tumor necrosis factor alpha (TNFα) and inhibited the disrupting effect of TNFα on the epithelial barrier function in these cells. Cholera toxin (CTX)-induced mouse intestinal fluid secretion was significantly reduced by the administration of Cesinex(®) or tannic acid. Cesinex(®) has high antioxidant capacity. CONCLUSIONS: Cesinex(®) demonstrates efficacy and a good safety profile in the treatment of diarrhea. The broad-spectrum antidiarrheal effect of Cesinex(®) can be attributed to a combination of factors: its ability to improve the epithelial barrier properties, to inhibit intestinal fluid secretion, and the high antioxidant capacity.

Functional regulation of cystic fibrosis transmembrane conductance regulator-containing macromolecular complexes: a small-molecule inhibitor approach.

CFTR (cystic fibrosis transmembrane conductance regulator) has been shown to form multiple protein macromolecular complexes with its interacting partners at discrete subcellular microdomains to modulate trafficking, transport and signalling in cells. Targeting protein-protein interactions within these macromolecular complexes would affect the expression or function of the CFTR channel. We specifically targeted the PDZ domain-based LPA2 (type 2 lysophosphatidic acid receptor)-NHERF2 (Na+/H+ exchanger regulatory factor-2) interaction within the CFTR-NHERF2-LPA2-containing macromolecular complexes in airway epithelia and tested its regulatory role on CFTR channel function. We identified a cell-permeable small-molecule compound that preferentially inhibits the LPA2-NHERF2 interaction. We show that this compound can disrupt the LPA2-NHERF2 interaction in cells and thus compromises the integrity of macromolecular complexes. Functionally, it elevates cAMP levels in proximity to CFTR and upregulates its channel activity. The results of the present study demonstrate that CFTR Cl- channel function can be finely tuned by modulating PDZ domain-based protein-protein interactions within the CFTR-containing macromolecular complexes. The present study might help to identify novel therapeutic targets to treat diseases associated with dysfunctional CFTR Cl- channels.

Wide space sowing achieved high productivity and effective nitrogen use of irrigated wheat in South Shanxi, China.

Wheat (Triticum aestivum L.) is a staple crop worldwide, and its yield has improved since the green revolution, which was attributed to chemical nitrogen (N) fertilizer application. However, regular N application decreases N use efficiency (NUE, the ratio of grain dry matter yield to N supply from soil and fertilizer). Various practices have been implemented to maintain high crop yield and improve NUE. Nowadays, the enhanced sowing method, i.e., wide space sowing (WS), has improved the productivity of wheat crops. However, how the sowing method and N application rate affect N use and yield productivity has not been fully elucidated. Field experiments with treatments using two sowing methods (WS, and drill sowing, DS) and four N application rates (0, 180, 240, and 300 kg ha-1, represented as N0, N180, N240, and N300, respectively) were conducted from 2017 to 2019. The results showed that grain yield under WS was 13.57-16.38% higher than that under DS. The yield advantage under WS was attributed to an increased ear number. Both the higher stem and productive stem percentage accounted for the increased ear number under WS. Higher total N quantity and larger leaf area index at anthesis under WS contributed to higher dry matter production, resulting in higher grain yield. Higher dry matter production was due to pre-anthesis dry weight and post-anthesis dry weight. The wheat crop under WS had a 12.44-15.00% higher NUE than that under DS. The increased NUE under WS was attributed to higher N uptake efficiency (the ratio of total N quantity at maturity to N supply from soil and fertilizer), which was the result of greater total N quantity. The higher total N quantity under WS was due to both higher pre-anthesis N uptake and post-anthesis N uptake. Remarkably, compared to DS with 240 kg N ha-1, WS with 180 kg N ha-1 had almost equal grain yield, dry matter, and total N quantity. Therefore, wheat crops under WS could achieve both high NUE and grain yield simultaneously with only moderate N fertilizer in South Shanxi, China.