Multi-medium residues and ecological risk of herbicides in a typical agricultural watershed of the Mollisols region, Northeast China.

The widespread use of herbicides impacts non-target organisms, promotes weed resistance, posing a serious threat to the global goal of green production in agriculture. Although the herbicide residues have been widely reported in individual environmental medium, their presence across different media has received scant attention, particularly in Mollisols regions with intensive agricultural application of herbicides. A systematic investigation was conducted in this study to clarify the occurrence of herbicide residues in soil, surface water, sediments, and grains from a typical agricultural watershed in the Mollisols region of Northeast China. Concentrations of studied herbicides ranged from 0.30 to 463.49 µg/kg in soil, 0.31-29.73 µg/kg in sediments, 0.006-1.157 µg/L in water, and 0.32-2.83 µg/kg in grains. Among these, Clomazone was the most priority herbicide detected in soil, sediments, and water, and Pendimethalin in grains. Crop types significantly affected the residue levels of herbicides in grains. Clomazone posed high ecological risks in soil and water, with 86.4 % of water samples showing high risks from herbicide mixtures (RQ > 1). These findings aid in enhancing our comprehension of the pervasive occurrence and potential ecological risks of herbicides in different media within typical agricultural watersheds, providing detailed data to inform the development of targeted mitigation strategies.

Progress in nanoparticle-based regulation of immune cells.

Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

[Characteristics of Heavy Metal Pollution in Farmland Soil of the Yangtze River Economic Belt Based on Bibliometric Analysis].

The Yangtze River Economic Belt is one of the major strategic development regions in China. It is of great significance to clarify the characteristics and sources of heavy metal pollution in farmland soil of the Yangtze River Economic Belt for the prevention and control of heavy metal pollution and to ensure safe agricultural production. After collecting extensive literature data, we analyzed the pollution characteristics, environmental risk, and potential sources of heavy metals (Cd, Cr, Hg, As, Pb, Cu, Zn, and Ni) in farmland soil of the Yangtze River Economic Belt through the integrated use of spatial and geo-accumulation index analyses. The results showed that:① the proportion of soil samples exceeding the risk screening values for soil contamination of agricultural land of Cd, Cu, Pb, Hg, Zn, and As were 39.8%, 18.5%, 8.3%, 6.9%, 6.9%, and 6.4%, respectively. Compared with the risk standard, soil Cd had the highest rate of exceeding the standard. ② The contents of Cr, Cu, Zn, and Ni in the upper reaches were higher than those in the middle and lower reaches, and the contents of Cd, As, and Pb in the middle reaches were higher than those in the upper and lower reaches. ③ The results of the geo-accumulation index analysis showed that the contamination degree of the eight heavy metals decreased in the order of Cd(0.42)>Hg(-0.28)>Pb(-0.32)>Zn(-0.39)>Cu(-0.42)>Cr(-0.7)>As(-0.81)>Ni(-0.73), where the accumulation risk of soil Cd and Hg was relatively higher. ④ Higher environmental background and mining activities were the main factors affecting the accumulation of heavy metals in soils in the upper and middle reaches. By contrast, rapid urbanization, industrial production, and intensive agricultural activities were the main factors affecting the heavy metal accumulation in soils in the middle and lower reaches. In view of the current status and control needs of heavy metal pollution in the Yangtze River Economic Belt, it is recommended to strengthen source prevention and control and to also carry out hierarchical control and regional classification management of heavy metal pollution in farmland soils according to the degree of heavy metal pollution, geological background, and quality of agricultural products. The ultimate objective of this research was to archive the farmland soil environmental quality safety and agricultural green sustainable production in the Yangtze River Economic Belt.

MIL-101-Cr/Fe/Fe-NH2 for Efficient Separation of CH4 and C3H8 from Simulated Natural Gas.

Adsorptive separation based on porous solid adsorbents has emerged as an excellent effective alternative to energy-intensive conventional separation methods in a low energy cost and high working capacity manner. However, there are few stable mesoporous metal-organic frameworks (MOFs) for efficient purification of methane from other light hydrocarbons in natural gas. Herein, we report a series of stable mesoporous MOFs, MIL-101-Cr/Fe/Fe-NH2, for efficient separation of CH4 and C3H8 from a ternary mixture CH4/C2H6/C3H8. Experimental results show that all three MOFs possess excellent thermal, acid/basic, and hydrothermal stability. Single-component adsorption suggested that they have high C3H8 adsorption capacity and commendable selectivity for C3H8 and C2H6 over CH4. Transient breakthrough experiments further certified the ability of direct separation of CH4 from simulated natural gas and indirect recovery of C3H8 from the packing column. Theoretical calculations illustrated that the van der Waals force proportional to the molecular weight is the key factor and that the structural integrity and defect can impact separation performances.

One and Two-Photon Excited Fluorescence Optimization of Metal-Organic Frameworks with Symmetry-Reduced AIEgen-Ligand.

By designing a tetraphenylethylene (TPE)-based AIEgen-ligand with reduced symmetry, we obtained two alkaline-earth metal-based MOFs (LIFM-102 and LIFM-103) with dense packing structures and low porosity as proved by single-crystal X-ray diffraction and CO2 sorption data. Excitingly, the desolvated MOFs with rigid environment and reduced lattice free solvent exhibit high quantum yields (QY, 64.9 % and 79.4 %) and excellent two-photon excited photoluminescence (TPA cross-sections, 2946.6 GM and 2899.0 GM), while maintaining the external-stimuli-responsive properties suitable for anticounterfeit fields. The effect of ligand conformation was validated by comparing the structure and fluorescence properties of the samples before and after desolvation and further verified by theoretical calculations. This work expands the study on TPE-cored materials to symmetry-reduced ligand and might bring forward novel structures and excellent photoluminescent properties in the future.

High-Temperature and Dynamic RGB (Red-Green-Blue) Long-Persistent Luminescence in an Anti-Kasha Organic Compound.

Organic LPL (long-persistent luminescence) materials have sparked extensive research interest due to the ultralong-lived triplet states. Although numerous organic LPL materials have been reported, most of the triplet emission was static and monotonous. Therefore, LPL materials with dynamic triplet emission are urgently required. A triamino-s-triazine derivative 1 with dynamic LPL was fabricated. The single-crystal structure shows that the abundant intermolecular interactions and small free volume restrict the molecular motion and avoid the quenchers. Spectral and theoretical calculations upheld the existence of multiple excited states in 1, and the migration of electrons between multiple excited states is very sensitive to external stimuli. By modulating the stimulus, the residence of electrons in different triplet states can be manipulated to achieve RGB LPL. Importantly, blue LPL was achieved by manipulating the anti-Kasha emission. And the red LPL can still be observed at high temperature.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Environmental capacity of heavy metals in intensive agricultural soils: Insights from geochemical baselines and source apportionment.

Soil environmental capacity (EC) of heavy metals (HMs) can be used as an index to evaluate the pollution status of HMs and to provide basic data for HM remediation. However, the commonly used soil EC for HMs usually are prone to bias due to the lack of local background values (BVs) and the consideration of the contribution from various HM sources. Here, a modified method was proposed to estimate the soil EC by integrating the establishment of local BVs and the quantitative evaluation of contributions from HM sources in an intensive agricultural area of Shouguang city, China. The local BVs of HMs were established using the relative cumulative frequency distribution method. The source-specific EC was quantified based on the local BVs and the contributions of HM sources identified by receptor model and variable importance analysis. Results showed that the average BV values of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn were 7.67, 0.10, 62.84, 21.17, 0.031, 28.38, 19.25, and 59.60 mg kg-1, respectively, in the study area. The source-specific EC of Cd, Cu, Hg, and Zn were higher than their current EC, indicating an underestimation of soil capacity of HMs by the traditional method. The EC of HMs in these soils was generally medium indicated by their comprehensive EC index (PI) (PI >0.7), suggesting a low risk level of the targeted HMs. According to indexes such as the individual metal index (Pi) and enrichment factor (EF), special attention should be paid to Cd and Zn due to their low capacity (Pi <0.7) and high accumulation (EF > 2) in some points across this area. Altogether, our findings suggested that the modified method had a better capability for evaluating and predicting the enrichment status of soil HMs, which can be helpful for formulating the targeted measures to control HM pollution in such intensive agricultural areas.

Phthalate pollution and migration in soil-air-vegetable systems in typical plastic agricultural greenhouses in northwestern China.

Phthalate pollution in plastic greenhouses (PGs) has aroused concerns. However, mechanisms and factors of vegetables planted in PGs (VPGs) accumulating phthalates from soil and air are unclear. To fill the gap, 19 PGs in Shaanxi, the largest vegetable production province in northwestern China, were selected to probe this issue. 35 soil samples, 48 air samples, and 26 VPG samples were collected in winter and summer. Medians of sum of 7 phthalate concentrations (∑7 PAEs) in PG soil, air, and VPGs were 73.9 µg kg-1, 5300 ng m-3, and 1053 µg kg-1 dry weight, respectively. ∑7 PAE concentrations in PG environmental media in winter were higher than summer, with the significant difference in VPGs. Sum concentrations of bis (2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) accounted for 76.8% and 82.3% of the ∑7 PAEs in soil and VPGs. DnBP and DEHP concentrations in VPGs were significantly correlated to those in air and soil, with correlation coefficients (R) of 0.89 and 0.96 to air and 0.68 and 0.59 to soil. Log-transformed soil-air partition coefficient (log KSA) and fugacity fraction (log ff) of DnBP decreased while log KSA and log ff of DEHP increased from winter to summer, though DnBP in soil volatilized to air while DEHP in air sank to soil within the year. These issues were caused by air temperature changes and the application of plastic films. Furthermore, DnBP concentrations in VPGs were positively correlated to KSA values of DnBP (R = 0.87) while those of DEHP were negative (R = -0.82). Therefore, VPGs could uptake more phthalates from air than from soil, especially for edible parts of leafy and solanaceous VPGs. Applying phthalates free agricultural films and precision management such as adjusting air temperature in PGs could be considered to ensure VPG safeties.

Spatiotemporal variation and sources of soil heavy metals along the lower reaches of Yangtze River, China.

Excessive accumulation of soil heavy metals (HMs) result in the deterioration of soil quality and reduction of agricultural productivity and safety. The accumulation status, temporal change, and sources of soil HMs were determined by large-scale field surveys in 2014 and 2019 in rapid urbanization and industrialization area along the lower reaches of the Yangtze River, China. Eighty-two surface soil samples were collected in 2014 and ninety-five surface soil samples and seven soil profiles (0-100 cm) were collected in 2019. The mean concentrations (in, mg kg-1) of As (10.17), Cd (0.33), Cr (86.38), Cu (38.22), Hg (0.11), Ni (37.67), Pb (43.95), and Zn (113.15) were greater than the corresponding background values. The concentrations of these 8 HMs significantly varied with site-specific distributions depending on nearby landscape patterns with decreasing order: agricultural soil around industrial > agricultural soil > fallow soil. Cd and Hg were found to be priority pollutants due to their greater accumulations in this study area. Combined analyses of principal component analysis and positive matrix factorization model addressed source apportionment of soil HMs. Industrial activities, parent materials, and agricultural and traffic activities were three major sources and their contributions were 35.56%, 35.20%, and 29.23%, respectively. The concentrations of soil As, Cd, Cr and Pb increased with time. This study elucidates how changes in land uses and time affect soil HMs and provides reasonable suggestions for the effective reduction of HM contamination in economically and industrially developed areas of China, and elsewhere.

High Water Adsorption MOFs with Optimized Pore-Nanospaces for Autonomous Indoor Humidity Control and Pollutants Removal.

The indoor air quality is of prime importance for human daily life and health, for which the adsorbents like zeolites and silica-gels are widely used for air dehumidification and harmful gases capture. Herein, we develop a pore-nanospace post-engineering strategy to optimize the hydrophilicity, water-uptake capacity and air-purifying ability of metal-organic frameworks (MOFs) with long-term stability, offering an ideal candidate with autonomous multi-functionality of moisture control and pollutants sequestration. Through variant tuning of organic-linkers carrying hydrophobic and hydrophilic groups in the pore-nanospaces of prototypical UiO-67, a moderately hydrophilic MOF (UiO-67-4Me-NH2 -38 %) with high thermal, hydrolytic and acid-base stability is screened out, featuring S-shaped water sorption isotherms exactly located in the recommended comfortable and healthy ranges of relative humidity for indoor ventilation (45 %-65 % RH) and adverse health effects minimization (40-60 % RH). Its exceptional attributes of water-uptake working capacity/efficiency, contaminants removal, recyclability and regeneration promise a great potential in confined indoor environment application.

Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China. AIM: To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients. METHODS: This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A (n = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96th week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates. RESULTS: For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 vs 5.73 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% vs 77.97%, 31.00% vs 27.27%, and 20.22% vs 15.79%, respectively, in Group A vs Group B; P > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 vs 4.70 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% vs 94.12% in Group A vs Group B, respectively; P > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% vs 84.57% in Group A vs Group B, respectively; P > 0.05), and similar incidences of adverse events were observed (106 vs 104 in Group A vs Group B, respectively; P > 0.05). CONCLUSION: Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.

Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy.

Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an 'adaptor' while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models.

Atmospheric phthalate pollution in plastic agricultural greenhouses in Shaanxi Province, China.

Phthalate pollution in soil and vegetables in plastic agricultural greenhouses has attracted wide concern. Investigating airborne phthalates in this environment can improve understanding of air-soil or air-vegetable phthalate migration. However, studies of phthalates in plastic agricultural greenhouse air are rare. To fill this gap, 25 gas-phase and 23 particle-phase samples were collected from 12 typical plastic greenhouses in Shaanxi. 16 types of phthalates were measured by a gas chromatography-mass spectrometry system (GC-MS) to analyse their pollution features and variations. Results showed that in the air of the plastic greenhouses, the median concentration of the sum of sixteen type phthalates (∑16 phthalates) was 5305 ng m-3, with 5th-95th value of 1214-9616 ng m-3. Phthalates in gas-phase samples were over 100 times higher than the levels in particle-phase samples. Air phthalate concentrations in the plastic greenhouses were higher than those in the control groups (P < 0.05). Air bis (2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) accounted for 66.9% and 29.3% of total ∑16 phthalate concentrations, respectively. Air phthalate concentrations in the plastic greenhouses in winter were 1.1-5.3 times higher than the levels in summer respectively (P < 0.05). Gas-particle partition coefficients (KP) values of DEHP in summer (median of 1.52 × 10-4 m3 µg-1) were higher than KP values of DnBP in summer (0.60 × 10-4 m3 µg-1). Log-transformed KP values of DnBP and DEHP were linear correlated to the reciprocal of air temperatures, respectively (P < 0.05).

An All-in-One Nanomedicine Consisting of CRISPR-Cas9 and an Autoantigen Peptide for Restoring Specific Immune Tolerance.

Nanotechnology has shown great promise in treating diverse diseases. However, developing nanomedicines that can cure autoimmune diseases without causing systemic immunosuppression is still quite challenging. Herein, we propose an all-in-one nanomedicine comprising an autoantigen peptide and CRISPR-Cas9 to restore specific immune tolerance by engineering dendritic cells (DCs) into a tolerogenic phenotype, which can expand autoantigen-specific regulatory T (Treg) cells. In brief, we utilized cationic lipid-assisted poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles to simultaneously encapsulate an autoimmune diabetes-relevant peptide (2.5mi), a CRISPR-Cas9 plasmid (pCas9), and three guide RNAs (gRNAs) targeting costimulatory molecules (CD80, CD86, and CD40). We demonstrated that the all-in-one nanomedicine was able to effectively codeliver these components into DCs, followed by simultaneous disruption of the three costimulatory molecules and presentation of the 2.5mi peptide on the genome-edited DCs. The resulting tolerogenic DCs triggered the generation and expansion of autoantigen-specific Treg cells by presenting the 2.5mi peptide to CD4+ T cells in the absence of costimulatory signals. Using autoimmune type 1 diabetes (T1D) as a typical disease model, we demonstrated that our nanomedicine prevented autoimmunity to islet components and inhibited T1D development. Our all-in-one nanomedicine achieved codelivery of CRISPR-Cas9 and the peptide to DCs and could be easily applied to other autoimmune diseases by substitution of different autoantigen peptides.

Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy.

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.

Expression of BACE1 in the Rat Carotid Body.

This study explored the expression of BACE1 (ß-amyloid precursor protein cleaving enzyme 1) in the rat carotid body and the effect of CIH (cyclic intermittent hypoxia) on the expression of BACE1. We found that BACE1 was expressed in the rat carotid body and located in the nerve endings and type II cells but not in type I cells. CIH reduced BACE1 level in the carotid body, and reoxygenation or ROS scavenger alleviated this reduction. Furthermore, we found that CIH augmented the mRNA level of PGC-1α but attenuated the mRNA level of BACE1 in the carotid body. Taken together, our results suggest that CIH promotes the production of ROS that upregulates the level of PGC-1α, which may in turn inhibits the transcription of BACE1, and that a reduction in the BACE1 level may be related to CIH-induced reversible and ROS-dependent carotid body plasticity. Our study provides a new candidate molecule for further study of the mechanism of carotid body plasticity.

Characterization of Group I Metabotropic Glutamate Receptors in Rat and Human Adrenal Glands.

Glutamate and its receptors have been demonstrated to promote both basal and nicotine-evoked catecholamine release in bovine chromaffin cells. Multiple glutamate receptors, including metabotropic glutamate receptors (mGluRs), are found in the adrenal glands of several species, as well as in chromaffin cells. However, there is limited information available regarding the expression of glutamate metabotropic receptor (GRM)1-8 mRNAs and the detailed localization of group I mGluRs (mGluR1 and mGluR5) in the rat and human adrenal cortex and medulla. Therefore, we examined mRNA expression of GRM1-8 subunits using reverse transcription-polymerase chain reaction (RT-PCR) and the distribution of mGluR1 and mGluR5 by immunostaining. The results showed that the GRM1-8 mRNAs were expressed in both the cortex and medulla of rat and human adrenal glands with the exception of GRM1, which was not detectable in the rat adrenal cortex. Immunostaining of mGluR1 revealed that it was localized only in the adrenal medulla of rats but was present in both the adrenal cortex and medulla in humans. In the adrenal medulla, the central part of the adrenal glands, mGluR1 was detected in chromaffin cells but not in nerve fibers and ganglion cells. Immunoactivity of mGluR5 was visible in the capillary wall throughout the adrenal cortex and medulla in rat and human samples. Its immunoactivity was also observed in ganglion cells in the rat adrenal medulla. There was no mGluR5 immunoactivity detected in chromaffin cells and nerve fibers in the rat and human adrenal medulla. Using dissected rat adrenal medulla as a model, we found that treatment with a mGluR1 agonist activated extracellular signal-regulated kinase (ERK) 1/2 and increased the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Moreover, these results showed that mGluR1 signaling was involved in hypoxia-induced upregulation of TH in the rat adrenal medulla. This study shows the expression of GRM1-8 mRNAs in rat and human adrenal glands and indicates that glutamate, through the activation of mGluRs, may play various physiological roles in the adrenal gland. Furthermore, mGluR1 may be involved in catecholamine biosynthesis by regulating TH, and mGluR5 may affect cortical and medullar hormone levels by regulating microvascular function.