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Drought can greatly impact the biodiversity of an ecosystem and play a crucial role in regulating its functioning. However, the specific mechanisms by which drought mediate the biodiversity effect (BE) on community biomass in above- and belowground through functional traits remain poorly understood. Here, we conducted a common garden experiment in a greenhouse, which included two plant species richness levels and two water addition levels, to analyze the effects of biodiversity on aboveground biomass (AGB), belowground biomass (BGB) and total biomass (TB), and to quantify the relationship between BEs and functional traits under drought conditions. Our analysis focused on partitioning BEs into above- and belowground complementarity effect (CE) and selection effect (SE) at the species level, which allowed us to better understand the impacts of biodiversity on community biomass and the underlying mechanisms. Our results showed that plant species richness stimulated AGB, BGB and TB through CEs. Drought decreased AGB, BGB and TB, simultaneously. In addition, the aboveground CE was positively associated with the variation in plant height. SEs in above- and belowground were negatively correlated with the community mean plant height and root length, respectively. Furthermore, drought weakened the aboveground CE by decreasing variation in plant height, resulting in a reduction in AGB and TB. Our findings demonstrate that the complementarity of species is an important regulator of community biomass in above- and belowground, the dynamics of biomass under environmental stress are associated with the response of sensitive compartments. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain‐gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA‐ and DR‐related drugs for digestive system diseases. [ABSTRACT FROM AUTHOR]

Ion channels and transporters are ubiquitously expressed on cell membrane, which involve in a plethora of physiological process such as contraction, neurotransmission, secretion and so on. Ion channels and transporters is of great importance to maintaining membrane potential homeostasis, which is essential to absorption of nutrients in gastrointestinal tract. Most of nutrients are electrogenic and require ion channels and transporters to absorb. This review summarizes the latest research on the role of ion channels and transporters in regulating nutrient uptake such as K+ channels, Ca2+ channels and ion exchangers. Revealing the mechanism of ion channels and transporters associated with nutrient uptake will be helpful to provide new methods to diagnosis and find potential targets for diseases like diabetes, inflammatory bowel diseases, etc. Even though some of study still remain ambiguous and in early stage, we believe that ion channels and transporters will be novel therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

The inflammasome is a multimeric protein complex located in the cytoplasm that is activated by many factors and subsequently promotes the release of proinflammatory factors such as interleukin (IL)-1β and IL-18, resulting in a series of inflammatory responses that ultimately lead to the occurrence of various diseases. The Nod-like receptor protein 3 (NLRP3) inflammasome is the most characteristic type and the most widely studied among many inflammasomes. Activation of the NLRP3 inflammasome is closely related to the occurrence of many diseases, such as Alzheimer's disease. At present, a large number of studies have focused on the mechanisms underlying the activation of the NLRP3 inflammasome. Plenty of articles have reported the activation of the NLRP3 inflammasome by various ions, such as K+ and Na+ reflux and Ca2+ influx. However, few articles have reviewed the effects of various ion channels on the activation of the NLRP3 inflammasome and the relationship between the diseases caused by these proteins. This article mainly summarizes the relationship between intracellular and extracellular ion activities and ion channels and the activation of the NLRP3 inflammasome. We also provide a general summary of the diseases of each system caused by NLRP3 activation. We hope that more research will provide options for the treatment of diseases driven by the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Nitrogen deposition and biodiversity alter plant flowering phenology through abiotic factors and functional traits. However, few studies have considered their combined effects on flowering phenology. A common garden experiment with two nitrogen addition levels (0 and 6 g N m−2 year−1) and five species richness levels (1, 2, 4, 6, and 8) was established. We assessed the effects of nitrogen addition and plant species richness on three flowering phenological events of Medicago sativa L. via changes in functional traits, soil nutrients, and soil moisture and temperature. The first flowering day was delayed, the last flowering day advanced, and the flowering duration shortened after nitrogen addition. Meanwhile, the last flowering day advanced, and flowering duration shortened along plant species richness gradients, with an average of 0.64 and 0.95 days change per plant species increase, respectively. Importantly, it was observed that plant species richness affected flowering phenology mainly through changes in plant nutrient acquisition traits (i.e., leaf nitrogen and carbon/nitrogen ratio). Our findings illustrate the non-negligible effects of intraspecific variation in functional traits on flowering phenology and highlight the importance of including functional traits in phenological models to improve predictions of plant phenology in response to nitrogen deposition and biodiversity loss. [ABSTRACT FROM AUTHOR]

Background and Aims Nitrogen enrichment affects biodiversity, plant functional traits and ecosystem functions. However, the direct and indirect effects of nitrogen addition and biodiversity on the links between plant traits and ecosystem functions have been largely overlooked, even though multidimensional characteristics of plant functional traits are probably critical predictors of ecosystem functions. Methods To investigate the mechanism underlying the links between plant trait identity, diversity, network topology and above- and below-ground biomass along a plant species richness gradient under different nitrogen addition levels, a common garden experiment was conducted in which those driving factors were manipulated. Key Results The study found that nitrogen addition increased above-ground biomass but not below-ground biomass, while species richness was positively associated with above- and below-ground biomass. Nitrogen addition had minor effects on plant trait identity and diversity, and on the connectivity and complexity of the trait networks. However, species richness increased above-ground biomass mainly by increasing leaf trait diversity and network modularity, and enhanced below-ground biomass through an increase in root nitrogen concentration and network modularity. Conclusions The results demonstrate the mechanistic links between community biomass and plant trait identity, diversity and network topology, and show that the trait network architecture could be an indicator of the effects of global changes on ecosystem functions as importantly as trait identity and diversity. [ABSTRACT FROM AUTHOR]

Natural infrastructure is essential in reducing thermal discomfort caused by the urban heat island (UHI) effect. Optimizing and planning green and blue spaces can help establish nature-based urban heat mitigation strategies that benefit sustainable urban development. Most current studies on urban heat mitigation have focused on the single heat reduction effect of green space or blue space, while there has been a lack of research on the combined cooling effects of blue and green spaces. Moreover, existing heat mitigation models and methods cannot directly guide the optimization of blue–green spatial patterns at the urban scale. This has led to an unclear relationship between heat mitigation effects and blue–green spatial patterns. Based on land use data, meteorological data, and biophysical information as inputs, this paper utilized the InVEST urban cooling model (UCM) and scenario analysis method to simulate urban heat mitigation patterns by setting up different blue–green space configuration scenarios. The relative contribution of blue–green space changes to the variation of heat mitigation benefits was quantitatively estimated using the difference comparison method, and the relationship between heat reduction effects and urban blue–green spatial patterns was elucidated using spatial analysis methods. The results show that the InVEST UCM captured some of the variability in the surface thermal response of Wuhan and can be applied to the modeling of urban heat mitigation patterns. Furthermore, they show that consideration of the cooling effect of water evaporation can improve the simulation accuracy to some extent. In Wuhan, there were regional differences in heat mitigation patterns and the heat mitigation effect was significantly higher in the suburbs than in the city. Additionally, urban parks, lakes, and mountains with surface or block distribution had noticeable cooling benefits. Finally, the scenario simulation results demonstrate that green space was more efficient at mitigating heat, while blue space was more critical for the geographical partitioning of the UHI. These findings can provide a reference for the planning and optimal management of urban blue and green spaces, as well as for the design of heat reduction policies. [ABSTRACT FROM AUTHOR]

Exosomes are membranous vesicles containing RNA and proteins that are specifically secreted in vivo. Exosomes have many functions, such as material transport and signal transduction between cells. Many studies have proven that exosomes can not only be used as biomarkers for disease diagnosis but also as carriers to transmit information between cells. Exosomes participate in a variety of physiological and pathological processes, including the immune response, antigen presentation, cell migration, cell differentiation, and tumour development. Differences in exosome functions depend on cell type. In recent years, exosome origin, cargo composition, and precise regulatory mechanisms have been the focus of research. Although exosomes have been extensively reported in digestive tumours, few articles have reviewed their roles in inflammatory diseases of the digestive system, especially inflammatory-related diseases (such as reflux oesophagitis, gastritis, inflammatory bowel disease, hepatitis, and pancreatitis). This paper briefly summarizes the roles of exosomes in inflammatory diseases of the digestive system to provide a basis for research on the mechanism of inflammatory diseases of the digestive system targeted by exosomes. [ABSTRACT FROM AUTHOR]

P2X receptors (P2XRs) are trimeric, non-selective cation channels activated by extracellular ATP and widely distributed in the digestive system. P2XRs have an important role in the physiological function of the digestive system, such as neurotransmission, ion transports, proliferation and apoptosis, muscle contraction, and relaxation. P2XRs can be involved in pain mechanisms both centrally and in the periphery and confirmed the association of P2XRs with visceral pain. In the periphery, ATP can be released as a result of tissue injury, visceral distension, or sympathetic activation and can excite nociceptive primary afferents by acting at homomeric P2X(3)R or heteromeric P2X(2/3)R. Thus, peripheral P2XRs, and homomeric P2X(3) and/or heteromeric P2X(2/3)R in particular, constitute attractive targets for analgesic drugs. Recently studies have shown that P2XRs have made significant advances in inflammation and cancer. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. It is believed that with the further study of P2XRs and its subtypes, P2XRs and its specific antagonists will be expected to be widely used in the treatment of human digestive diseases in the future. [ABSTRACT FROM AUTHOR]

Neurotransmitters are special molecules that serve as messengers in chemical synapses between neurons, cells, or receptors, including catecholamines, serotonin, dopamine, and other neurotransmitters, which play an important role in both human physiology and pathology. Compelling evidence has indicated that neurotransmitters have an important physiological role in various digestive diseases. They act as ligands in combination with central or peripheral receptors, and transmits signals through chemical synapses, which are involved in regulating the physiological and pathological processes of the digestive tract organs. For instance, neurotransmitters regulate blood circulation and affect intestinal movement, nutrient absorption, the gastrointestinal innate immune system, and the microbiome. In this review, we will focus on the role of neurotransmitters in the pathogenesis of digestive tract diseases to provide novel therapeutic targets for new drug development in digestive diseases. [ABSTRACT FROM AUTHOR]

Substantial research has revealed that peroxisome proliferator-activated receptor-gamma (PPARG) plays a critical role in glucose homeostasis and lipid metabolism, and recent studies have shown different effects in the progression of different tumors. However, the role of PPARG and its target gene in clear cell renal cell carcinoma (ccRCC) are incompletely understood. Clinical data revealed abnormal glucolipid metabolism in primary ccRCC samples. In addition, transcriptional profiling indicated that PPARG expression was positively correlated, whereas Six2 expression was negatively correlated with the overall survival of ccRCC patients. Staining showed that PPARG was mainly expressed in tumor cell cytoplasm, and Six2 was localized to the nuclei. In a ccRCC cell line, PPARG activation promoted cell apoptosis, inhibited cell migration and proliferation, and reduced Six2 expression. Mechanistically, overexpressing Six2 downregulated E-cadherin expression and cell apoptosis, but PPARG activation reversed those effects. Taken together, PPARG promotes apoptosis and suppresses the migration and proliferation of ccRCC cells by inhibiting Six2. These findings reveal that the PPARG/Six2 axis acts as a central pathobiological mediator of ccRCC formation and as a potential therapeutic target for the treatment of patients with ccRCC. [ABSTRACT FROM AUTHOR]

It has been generally accepted that alternatively activated macrophages (M2), which can be induced by type 2 cytokines such as IL-4, is responsible for tissue repair. However, the function of JNK in IL-4-induced M2 macrophage polarization remains unclear. Here, we demonstrated that M0 macrophages can be polarized into M2 status in response to IL-4 stimulation with the increased expression of the M2-specific molecular markers. We also found that IL-4 induced higher expression of JNK and transcription factor c-Myc in M2 macrophages. Our Q-PCR and Western blot results showed that JNK increased the expression of c-Myc and M2 markers Arg1, Mrc1. We also demonstrated c-Myc was the downstream of IL-4-JNK pathway. Further, the depletion of c-Myc, Arg1 and Mrc1 could inhibit the migration ability of M2 macrophages. Taken together, our data establishes a new role for JNK signaling in IL-4-induced alternative activation of macrophages and may provide a novel strategy for immune therapy. [ABSTRACT FROM AUTHOR]

The purpose of our study is to clarify the effects of microRNA-129-5p (miR-129-5p) in cellular processes correlated with cancer development and progression of Glioblastoma (GBM) cell by regulating FNDC3B. MiR-129-5p and FNDC3B expression in GBM tissues and tumor adjacent tissues were tested by quantitative real-time PCR. We validated the target relationship between miR-129-5p and FNDC3B by dual luciferase reporter gene system. MTT, colony formation, flow cytometry, Transwell and wound healing assays were used to analyze cell viability, proliferation, apoptosis, invasiveness and migration. The level of FNDC3B protein expression was detected by Western Blot. MiR-129-5p was downregulated in GBM tissues and cell lines, while FNDC3B was upregulated in GBM tissues. The result of luciferase reporter gene assay demonstrated that miR-129-5p could target FNDC3B by binding to the 3′ UTR. The overexpression of miR-129-5p or the inhibition of FNDC3B can both inhibit U87 cell viability, proliferation, migration and invasion, while promote cell apoptosis. Our results suggested that miR-129-5p could directly suppress FNDC3B, which might be one of potential mechanisms in inhibiting cell processes including viability, proliferation, migration and invasiveness of U87 cells. [ABSTRACT FROM AUTHOR]

Duty cycle is a key factor for analyzing exposure to the electromagnetic field from the wireless local area network (WLAN). In this letter, we provide an analytical method for calculating the duty cycle of WLAN in a busy period. It relates to the medium access control (MAC) mode, durations of frames, and the random back-off time. We investigate the rate change rules for calculating the durations of control frames. These durations are also crucial to the parameter setting of the instrument in measurement. We propose a calculation method of the random back-off time for a common scenario, where retransmission always occurs due to collisions or interferences. The duty cycles and the average exposure levels are analyzed and compared between two MAC modes for different transmission rates. Our study can be applied to the extrapolation and the measurement of exposure to WLAN, and compliance testing with safety guidelines. [ABSTRACT FROM PUBLISHER]

Non-small cell lung cancer (NSCLC) is the major cause of cancer-related lethality among human cancer patients globally, and the poor prognosis of this cancer is mainly explained by metastasis, so it is essential to find out the molecule mechanisms and a novel therapeutic for NSCLC. A disintegrin and metalloprotease with thrombospondin motif 5 (ADAMTS5) belongs to the protease family. It has been reported to participate in tumor migration and invasion. In this study, we showed that the expression of ADAMTS5 was higher in lung cancer tissues by Western blot. The immunohistochemistry analysis was performed in 140 NSCLC cases, and the result indicated that ADAMTS5 was significantly associated with clinical pathologic variables. The Kaplan-Meier curve showed that the high expression of ADAMTS5 was related to poor prognosis of lung cancer patients. Wound healing assays and transwell migration assays revealed that the high expression of ADAMTS5 promoted the migration and invasion of NSCLC. In a word, our findings suggest that ADAMTS5 can regulate the migration and invasion of NSCLC and it may be a useful target of therapy in NSCLC. [ABSTRACT FROM AUTHOR]

Rice is the most important food crop in China and its production ranks first in three major grain crops which are wheat, rice and corn. Therefore, it is very important to understand planting area and growth of rice. Because change detection is time-sensitive, remote sensing data is often used as a data source for it. Most of widely-used change detection methods using TM image are at pixel level, or only use image of single time phase. Based on multi-temporal Landsat TM images, this research extracted change area of rice planting in Pingle County. The process explored the methods of calculating changes in intensity and determining the threshold. First, the paper selected images of heading stage and harvest stage as data sources, and except for crops, there are no significant changes of ground objects in a few months. Since the spectral characteristics of late rice in the two periods are different from those of other crops, the changes of the images at two stages in the same year could be used to extract the change area of rice planting. In the process, change vector analysis method, correlation coefficient method and vector similarity method were used to calculate the change intensity. Otsu method, minimum error rate method and the method based on double window with variable step size were used to determine the threshold of the change intensity map. The change area maps of rice planting extracted by nine combinations of the methods were compared. Comprehensive utilization of three methods for extracting changes could get change area of rice planting with higher accuracy. This paper chose minimum error rate method based on histogram curvature or the method based on double window with variable step size to determine the threshold. The intersection of change area based on change vector analysis method and change area based on correlation coefficient method could inhibit the pseudo change of river beach and mountain shadow. Then the rice area was extracted exactly according to the difference between NDVI values and the object-oriented method. In order to refine the change detection of rice planting areas, the change areas of all ground objects and the change area of rice planting in two years were intersected to get the final variation for rice planting area. The results showed that the inhibitory effect of change vector analysis method for river beach change was better than correlation coefficient method, and yet the inhibition effect of correlation coefficient method for mountain shadow was better than change vector analysis method. Besides, vector similarity method was sensitive to mountain shadow and had low sensitivity to paddy field change. Among the three threshold determination methods, minimum error rate method was more accurate than Otsu method and more stable than the method based on double window with variable step size. Finally, the overall accuracy of change detection for late rice's planting area in Pingle County reached 96.8% in confusion matrix for verification. The error of the change area was 2.85% compared with the statistical data. This method could effectively extract the change of rice planting area in Pingle County. [ABSTRACT FROM AUTHOR]

Sugarcane identification on specific parcels and the assessment of soil management practices are important for agro-ecological studies, greenhouse gas modeling, and agrarian policy development. Information on the sugarcane cultivation areas is of global economic and environmental significance. The study area is Guigang City located in the central area of Guangxi Province which is a good representation of the agricultural conditions. Traditional pixel-based analysis of remotely sensed data results in inaccurate identification of some crops due to pixel heterogeneity, mixed pixels, spectral similarity. The growing region of sugarcane in Guangxi Province is discrete, so the remote sensing spectral of sugarcane is vulnerable to be impacted on a variety of crops. There are certain difficulties in the use of multi-spectral remote sensing to extract sugarcane. Current techniques for mapping sugarcane are based mainly on MODIS satellite data and may not make full use of the texture characteristics. The objective of this research is to investigate the potential for the application of the China Environment Satellite HJ-1A/1B and Phenology in monitoring sugarcane cultivation areas in Guangxi province in southern China. In our approach, we explored several characteristics such as the time information, spectral characteristics and texture features, used an object-based image analysis method and decision tree method for mapping the sugarcane area over large areas based on multi-temporal China Environment Satellite HJ-1A/B Data. A CCD camera sensor with 30m spatial resolution on board the China Environment Satellite HJ-1A and B has both visible and near infrared bands and a revisit period of four days, thus the temporal Normalized Difference Vegetation Index (NDVI) can be obtained from HJ-1A and B data. A time series of the China Environment Satellite HJ-1A/B Data and DEM images was acquired in order to represent the wide range of pattern variation along the sugarcane crop cycle. Firstly, the phenology differences and between sugarcane and other crops, such as cassavas, rice, corn, in Guigang City were analyzed. Therefore the best recognition sessions of the sugarcane was proposed to be February, May, early August and December. Then, to derive the image objects, the multi-scale segmentation algorithm was used in Definiens Developer in which the classification rule set was established. The rule set consists of the Process Algorithm and Class Description which contain several membership functions of characteristic indexes. The useful characteristic indexes mapping the sugarcane from other crops are Spectral mean value, NDVI, Digital Evaluate Model (DEM) and Gray Level Co-occurrence Matrix (GLCM) homogeneity. Finally, the desired thematic map with sugarcane ready to harvest was generated. The mapping was then evaluated applying the confusion matrix method and Kappa statistics to the independent testing dataset which was composed of 102 field survey points and 48 point samples on Google Earth. The statistics indicated that the classification achieved an overall accuracy of 91.3% and a Kappa coefficient of 0.83. The results of this study show that the Object-Oriented method is very efficient for the sugarcane classification process to maximize elimination of other interfering factors and suggests that the China Environment Satellite HJ-1A/B has great potential in the development of an operational system for monitoring sugarcane growth in southern China. [ABSTRACT FROM AUTHOR]

The Han River Basin is a main agricultural production area and a water source for the middle route of the South-to-North Water Diversion Project in China. Over the past 20 years, human exploitation and ecological construction have disturbed the sustainability of land productivity in the Han River Basin. Theil–Sen trend analysis, Mann–Kendall statistical test, and Hurst index methods were applied to examine spatial–temporal trends and sustainability characteristics of land net primary productivity (NPP) change in the Han River Basin from 2001 to 2019 using MOD17A3 NPP product, natural, and socio-economic data obtained from Google Earth Engine (GEE). The findings demonstrated that the interannual variation of land NPP exhibited a fluctuating upward trend, with a more pronounced growth rate from 2001 to 2010 than from 2011 to 2019. The spatial heterogeneity of land NPP was evident, with high values in the west and low values in the east. Of the basin area, 57.82% presented a significant increase in land NPP, while only 0.96% showed a significant decrease. In the future, land NPP in the Han River Basin will present sustained growth. The results were also compared with Trends.Earth's calculations for the SDG 15.3.1 sub-indicator of land productivity. In addition, the spatial heterogeneity of factors influencing land NPP change was explored using a multiscale geographically weighted regression (MGWR) model. Precipitation and population count were the dominant factors in most regions. Besides, precipitation, population count, and human modification all exhibited inhibitory effects on the increase in land NPP except for elevation. The research can provide a scientific basis for tracking land degradation neutrality (LDN) progress and achieving sustainable socio-ecological development of the Han River Basin. [ABSTRACT FROM AUTHOR]

Autophagy is a process of degradation and catabolism in cells. By removing damaged or dysfunctional organelles, autophagy interacts with the ubiquitin-proteasome degradation system to jointly regulate cell function and energy homeostasis. Since autophagy plays a key role in physiology, disorders of the autophagy mechanism are associated with various diseases. Therefore, thorough understanding of the autophagy regulatory mechanism are crucially important in the diagnosis and treatment of diseases. To date, ion channels may affect the development and treatment of diseases by regulating autophagy, especially calcium-permeable ion channels, in the process of digestive system diseases. However, the mechanism by which calcium ions and their channels regulate autophagy is still poorly understood, thus emphasizing the need for further research in this field. The present review intends to discuss the association, mechanism and application of calcium ions, their channels and autophagy in the occurrence and development of digestive system diseases. [ABSTRACT FROM AUTHOR]

Tumors pose a major threat to human health and present with difficulties that modern medicine has yet to overcome. It has been demonstrated that the acid-base balance of the tumor microenvironment is closely associated with the dynamic balance in the human body and that it regulates several processes, such as cell proliferation and differentiation, intracellular enzyme activity, and cytoskeletal assembly and depolymerization. It has been well established that the regulation of intra- and extracellular pH depends on a series of functional ion transporters and hydrogen ion channels, such as the Na+/H+ exchanger (NHE) protein and thee Cl/HCO3- exchange protein, among which the NHE1 member of the NHE family has been attracting increasing attention in recent years, particularly in studies on the correlation between pH regulation and tumors. NHE1 is a housekeeping gene encoding a protein that is widely expressed on the surface of all plasma membranes. Due to its functional domain, which determines the pHi at its N-terminus and C-terminus, NHE1 is involved in the regulation of the cellular pH microenvironment. It has been reported in the literature that NHE1 can regulate cell volume, participate in the transmembrane transport of intracellular and extracellular ions, affect cell proliferation and apoptosis, and regulate cell behavior and cell cycle progression; however, research on the role of NHE1 in tumorigenesis and tumor development in various systems is at its early stages. The aim of the present study was to review the current research on the correlation between the NHE family proteins and various systemic tumors, in order to indicate a new direction for antitumor drug development with the pH microenvironment as the target. [ABSTRACT FROM AUTHOR]

Intracellular calcium (Ca2+) is a critical cell signaling component in gastrointestinal (GI) physiology. Cytosolic calcium ([Ca2+]cyt), as a secondary messenger, controls GI epithelial fluid and ion transport, mucus and neuropeptide secretion, as well as synaptic transmission and motility. The key roles of Ca2+ signaling in other types of secretory cell (including those in the airways and salivary glands) are well known. However, its action in GI epithelial secretion and the underlying molecular mechanisms have remained to be fully elucidated. The present review focused on the role of [Ca2+]cyt in GI epithelial anion secretion. Ca2+ signaling regulates the activities of ion channels and transporters involved in GI epithelial ion and fluid transport, including Cl- channels, Ca2+-activated K+ channels, cystic fibrosis (CF) transmembrane conductance regulator and anion/HCO3- exchangers. Previous studies by the current researchers have focused on this field over several years, providing solid evidence that Ca2+ signaling has an important role in the regulation of GI epithelial anion secretion and uncovering underlying molecular mechanisms. The present review is largely based on previous studies by the current researchers and provides an overview of the currently known molecular mechanisms of GI epithelial anion secretion with an emphasis on Ca2+-mediated ion secretion and its dysregulation in GI disorders. In addition, previous studies by the current researchers demonstrated that different regulatory mechanisms are in place for GI epithelial HCO3- and Cl- secretion. An increased understanding of the roles of Ca2+ signaling and its targets in GI anion secretion may lead to the development of novel strategies to inhibit GI diseases, including the enhancement of fluid secretion in CF and protection of the GI mucosa in ulcer diseases. [ABSTRACT FROM AUTHOR]

High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice. [ABSTRACT FROM AUTHOR]